BACKGROUND: Metabolic Syndrome (MS) is prevalant in China, especially according to the pediatric obesity group. Based on the MS-CHN2012 definition for Chinese children and adolescents the need to explore and establish a convienent MS screening become imminent. This study aims to investigate the optimal cut-off values, compare the accuracy for the (TriGlycerides (TG) to High-Density Lipoprotein Cholesterol (HDL-C)) (TG/HDL-C) ratio and Homeostasis Model Assessment Insulin Resistance (HOMA-IR) indexs to identify Metabolic Syndrome in obese pediatric population in China.. METHOD: A total sample of 976 children (female 286 male 690, BMI , = 95 percentile) aged from 6-16 years underwent a medical assessment including a physical examination and investigations of total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides, insulin, glucose, and oral glucose tolerance test to identify the components of Metabolic Syndrome. The validity and accuracy between TG/HDL-C ratio and ...

OBJECTIVE: Several methods have been proposed to evaluate insulin sensitivity from the data obtained from the oral glucose tolerance test (OGTT). However, the validity of these indices has not been rigorously evaluated by comparing them with the direct measurement of insulin sensitivity obtained with the euglycemic insulin clamp technique. In this study, we compare various insulin sensitivity indices derived from the OGTT with whole-body insulin sensitivity measured by the euglycemic insulin clamp technique. RESEARCH DESIGN AND METHODS: In this study, 153 subjects (66 men and 87 women, aged 18-71 years, BMI 20-65 kg/m2) with varying degrees of glucose tolerance (62 subjects with normal glucose tolerance, 31 subjects with impaired glucose tolerance, and 60 subjects with type 2 diabetes) were studied. After a 10-h overnight fast, all subjects underwent, in random order, a 75-g OGTT and a euglycemic insulin clamp, which was performed with the infusion of [3-3H]glucose. The indices of insulin ...

TY - JOUR. T1 - The association of SNP276G,T at adiponectin gene with circulating adiponectin and insulin resistance in response to mild weight loss. AU - Shin, M. J.. AU - Jang, Y.. AU - Koh, S. J.. AU - Chae, J. S.. AU - Kim, O. Y.. AU - Lee, J. E.. AU - Ordovas, J. M.. AU - Lee, J. H.. PY - 2006/12/21. Y1 - 2006/12/21. N2 - Objective:The purpose of this study was to determine whether common single nucleotide polymorphisms (SNPs) at the adiponectin (ADIPOQ) locus influence changes in circulating adiponectin and the features of insulin resistance in response to a weight loss intervention.Subjects:In total, 294 nondiabetic/overweight-obese Koreans participated in a clinical intervention study lasting 12 weeks involving a caloric reduction of -300kcal/day.Methods: Plasma adiponectin, blood lipids, glucose and insulin concentrations were measured at baseline and after weight loss. Insulin resistance was estimated by homeostasis model assessment insulin resistance (HOMA-IR) derived from fasting ...

TY - JOUR. T1 - Skeletal muscle insulin resistance. T2 - the interplay of local lipid excess and mitochondrial dysfunction. AU - Chow, Lisa S. AU - From, Arthur H. AU - Seaquist, Elizabeth R. PY - 2010/1. Y1 - 2010/1. N2 - This review explores the complex relationship between excess lipid exposure, mitochondrial dysfunction, and insulin resistance at the level of human skeletal muscle. Lipotoxicity, that is, the elevation of lipids and/or associated lipid metabolites within blood and tissues with subsequent metabolic derangement, has been proposed as a possible mechanism of skeletal muscle insulin resistance. Intravenous lipid infusion is a well-documented method of inducing insulin resistance. Although IMCL content has been correlated with insulin resistance, there is increasing evidence that lipid metabolites such as 4-HNE, DAG, ceramide, and LC-CoA may play a more significant role than TGs in producing skeletal muscle insulin resistance. The association between mitochondrial dysfunction and ...

Duncan, E, Walker, SJ, Ezzat, V, Wheatcroft, S, Li, J-M, Shah, A and Keamey, M (2006) Mild whole body insulin resistance and accelerated endothelial dysfunction: Increased reactive oxygen species derived from mitochondria during ageing despite preserved glycaemic control In: 79th Annual Scientific Session of the American-Heart-Association, 2006-11-12 - 2006-11-15, Chicago, IL. Full text not available from this repository ...

TY - JOUR. T1 - Adipose-Resident Group 1 Innate Lymphoid Cells Promote Obesity-Associated Insulin Resistance. AU - OSullivan, Timothy E.. AU - Rapp, Moritz. AU - Fan, Xiying. AU - Weizman, Orr El. AU - Bhardwaj, Priya. AU - Adams, Nicholas M.. AU - Walzer, Thierry. AU - Dannenberg, Andrew J.. AU - Sun, Joseph C.. PY - 2016. Y1 - 2016. N2 - Innate lymphoid cells (ILCs) function to protect epithelial barriers against pathogens and maintain tissue homeostasis in both barrier and non-barrier tissues. Here, utilizing Eomes reporter mice, we identify a subset of adipose group 1 ILC (ILC1) and demonstrate a role for these cells in metabolic disease. Adipose ILC1s were dependent on the transcription factors Nfil3 and T-bet but phenotypically and functionally distinct from adipose mature natural killer (NK) and immature NK cells. Analysis of parabiotic mice revealed that adipose ILC1s maintained long-term tissue residency. Diet-induced obesity drove early production of interleukin (IL)-12 in adipose ...

This trial is entitled "Bumetanide has a more favourable effect on insulin resistance than furosemide in patients with heart failure - a pilot study".

TY - JOUR. T1 - Dissociation between metabolic and vascular insulin resistance in aging. AU - Schulman, Ivonne Hernandez. AU - Zhou, Ming Sheng. AU - Jaimes, Edgar A.. AU - Raij, Leopoldo. PY - 2007/7. Y1 - 2007/7. N2 - Physiological actions of insulin via activation of the phosphatidylinositol 3-kinase/Akt pathway in the endothelium serve to couple regulation of hemodynamic and metabolic homeostasis. Insulin resistance, endothelial dysfunction, and hypertension increase in prevalence with aging. We investigated the metabolic and endothelial actions of insulin in 24- vs. 3-mo Sprague-Dawley rats. With the use of the hyperinsulinemic euglycemic clamp, the rate of glucose infusion necessary to maintain equivalent plasma glucose (5.5 mmol/l) was similar in 24- vs. 3-mo rats, as was fasting glucose (5.2 ± 0.33 vs. 4.4 ± 0.37 mmol/l; mean ± SE) and insulin (0.862 ± 0.193 vs. 1.307 ± 0.230 mg/l). Systolic blood pressure was higher in 24-mo rats (133 ± 5 vs. 110 ± 4 mmHg; P = 0.005). Endothelial ...

Researchers at the University of California, San Diego, School of Medicine have identified a particular subset of cells that are linked to obesity-associated insulin resistance, and that offer a promising new target for the treatment of diabetes. They showed that depletion of these cells, called CD11c-positive, in obese mice resulted in a reversal of obesity-associated insulin resistance.

Zhu, Caihong; Schwarz, Petra; Abakumova, Irina; Aguzzi, Adriano (2015). Unaltered prion pathogenesis in a mouse model of high-fat diet-induced insulin resistance. PLoS ONE, 10(12):e0144983. ...

View more ,Abstract: Insulin resistance ensues when normal physiological concentrations of insulin are unable to induce effective cellular insulin signalling and glucose uptake by insulin sensitive tissues. It is caused by several abnormalities that include; 1) an overabundance of circulating free fatty acids (and dyslipidaemia), 2) systemic inflammation caused by increased tissue and circulating pro-inflammatory cytokines, and, 3) over activation of the systemic and organ specific renin-angiotensin systems. Although usually associated with obesity, insulin resistance is not a condition that only afflicts obese individuals. Dyslipidaemia which is implicated in the aetiology of insulin resistance can be caused by adipose tissue expansion (obesity) or the increased consumption of lipogenic fructose which has profound effects on liver metabolism and serum lipid profiles. The primary reason fructose is implicated in insulin resistance is because it induces hepatic lipogenesis which would directly ...

In this issue of Circulation Research, Kim et al provide additional mechanistic insights into the link between obesity, innate immunity, vascular insulin resistance, and vascular inflammation in a murine model of high-fat diet-induced obesity.11 The authors induced obesity in C57BL6 mice by feeding them a high-fat diet for 8 weeks. Insulin signaling in aortic tissue from high-fat-fed mice was impaired, as measured by reduced phosphorylation of AKT and eNOS in response to insulin administration consistent with cellular evidence of insulin resistance. These effects on insulin resistance were associated with evidence of activation of NF-kB dependent inflammatory pathways, as indicated by increased phosphorylation of IKK-β and increased expression of the NF-κB dependent proinflammatory genes IL-6 and ICAM-1.. To further characterize the signaling pathway by which high-fat diet induces insulin resistance and proinflammatory vascular response, the authors did similar studies in TLR-4-null mice. ...

Michael Dube, for natap.org. Current dogma has early insulin resistance from ART blamed on protease inhibitors, and late insulin resistance attributed to lipoatrophy induced by nucleoside drugs. But studies in healthy subjects have suggested that at least some NRTIs may cause early insulin resistance as well.. The central finding presented by Marit van Vonderan from Amsterdam was that peripheral tissue insulin resistance (as measured by the gold standard hyperinsulinemic clamp procedure) occurred only occurred in subjects (all male) who initiated zidovudine-lamivudine plus Kaletra and not in those who received nevirapine plus Kaletra.. This ZDV-3TC associated insulin resistance was present at 3 months, a time point where limb fat was actually increased from baseline. At 24 months limb fat was down in the ZDV-3TC group, but this insulin resistance occurred well before limb fat had decreased, suggesting a more direct effect of the NRTI therapy. This data suggests that we need to pay attention to ...

Title: Myocardial Insulin Resistance and Cardiac Complications of Diabetes. VOLUME: 5 ISSUE: 2. Author(s):E. Dale Abel. Affiliation:Program in Human Molecular Biology and Genetics, Division of Endocrinology, Metabolism and Diabetes, University of Utah, 15 North 2030 East, Bldg. &# 533, Room 3410B, Salt Lake City, UT 84112, USA.. Keywords:insulin resistance, diabetes, obesity, myocardial energetics, cardiac hypertrophy, cardiac metabolism. Abstract: Cardiovascular disease is a major cause of mortality and morbidity in individuals with obesity, type 2 diabetes and the metabolic syndrome. The mechanisms for this are partially understood, but include increased atherosclerosis, hypercoagulability and increased hypertension. Epidemiological data suggests however, that a component of the excess cardiovascular mortality occurs independently of underlying coronary artery disease. Indeed, diabetes is an independent risk factor for the development of heart failure and the mechanisms responsible remain to ...

Aim Increased frequency of cardiovascular disease and its possible relations with insulin resistance have been reported in patients with inflammatory diseases. The aim of our study was to investigate insulin resistance and serum adiponectin levels as cardiovascular risk markers in patients with Behçets disease.. Method Study population consisted of 40 patients with Behçets disease (BD) and a control group composed of age, gender, body mass index-matched 46 healthy individuals. All patients were examined for signs of Behçets disease. Body mass index, waist and hip circumference were measured. Insulin resistance was evaluated using the homeostasis model assessment-insulin resistance method. Erythrocyte sedimentation rate (ESR), lipid profile, high sensitive CRP (hsCRP), adiponectin, TNF-α, IL-6 and IL-8 levels were measured.. Results Erythrocyte sedimentation rate, serum hsCRP and IL-6 levels were significantly higher in patients with BD than those in the controls (P = 0.001, P = 0.001, P = ...

Fingerprint Dive into the research topics of Adipose tissue insulin resistance in youth on the spectrum from normal weight to obese and from normal glucose tolerance to impaired glucose tolerance to type 2 diabetes. Together they form a unique fingerprint. ...

Fingerprint Dive into the research topics of Role of adipose tissue insulin resistance in the natural history of type 2 diabetes: Results from the san antonio metabolism study. Together they form a unique fingerprint. ...

TY - JOUR. T1 - Membrane-targeted phosphatidylinositol 3-kinase mimics insulin actions and induces a state of cellular insulin resistance. AU - Egawa, Katsuya. AU - Sharma, Prem M.. AU - Nakashima, Naoki. AU - Huang, Yi. AU - Huver, Evana. AU - Boss, Gerry R.. AU - Olefsky, Jerrold M.. PY - 1999/5/14. Y1 - 1999/5/14. N2 - Phosphatidylinositol (PI) 3-kinase plays an important role in various insulin-stimulated biological responses including glucose transport, glycogen synthesis, and protein synthesis. However, the molecular link between PI 3- kinase and these biological responses is still unclear. We have investigated whether targeting of the catalytic p110 subunit of PI 3-kinase to cellular membranes is sufficient and necessary to induce PI 3-kinase dependent signaling responses, characteristic of insulin action. We overexpressed Myc- tagged, membrane-targeted p110 (p110(CAAX)), and wild-type p110 (p110(WT)) in 3T3-L1 adipocytes by adenovirus-mediated gene transfer. Overexpressed p110(CAAX) ...

We assessed whether insulin sensitivity improved after renal denervation (RDN) for resistant hypertension. Twenty-three patients underwent a two-step hyperinsulinemic euglycemic clamp (HEC) with glucose tracer and labeled glucose infusion and oral glucose tolerance test (OGTT) before and 6 months after RDN. Eighteen patients had metabolic syndrome at baseline. Blood pressure declined significantly after RDN whereas fasting plasma glucose (5.9 ± 0.7 mmol/L), insulin (254 (88-797) pmol/L), C- peptide (2.4 (0.9-5.7) nmol/L) remained unchanged. Endogenous glucose release during HEC was less suppressed after RDN, suggesting a slight decrease in hepatic insulin sensitivity. During high-dose insulin infusion, whole-body glucose disposal was low and remained unchanged after RDN, indicating persistent peripheral insulin resistance. Area under the curve 0-120min for glucose and insulin during OGTT, Quantitative Insulin Sensitivity Check Index, Simple Index assessing Insulin Sensitivity oral glucose ...

We previously have shown that during the transition from NGT to IGT to T2DM, β-cell function progressively declines and peripheral insulin resistance progressively increases (31,35). Adipo-IR also is increased in patients with T2DM, but the natural history of its development as individuals progress from NGT to IGT to T2DM has been poorly studied. As recently reviewed (21), a number of indices of adipocyte insulin resistance have been proposed that are based on tracer turnover (i.e., labeled palmitate or glycerol) or FFA suppression during insulin infusion (euglycemic-hyperinsulinemic clamp) or OGTT. In the current study, we used the product of fasting plasma FFA and fasting plasma insulin concentrations as the index of Adipo-IR. Because the circulating plasma FFA concentration closely reflects the rate of peripheral lipolysis, Adipo-IR represents an index for adipose tissue resistance to the antilipolytic effect of insulin. The hyperbolic relationship between plasma insulin and FFA ...

insulin resistance - MedHelps insulin resistance Center for Information, Symptoms, Resources, Treatments and Tools for insulin resistance. Find insulin resistance information, treatments for insulin resistance and insulin resistance symptoms.

Inflammation plays a key role in the development and progression of type-2 diabetes (T2D), a disease characterised by peripheral insulin resistance and systemic glucolipotoxicity. Visceral adipose tissue (AT) is the main source of inflammation early in disease course. Macrophages are innate immune cells that populate all peripheral tissues, including AT. Dysregulated AT macrophage (ATM) responses to microenvironmental changes are at the root of aberrant inflammation and development of insulin resistance, locally and systemically. The inflammatory activation of macrophages is regulated at multiple levels: cell surface receptor stimulation, intracellular signalling, transcriptionally and metabolically. This review will cover the main mechanisms involved in AT inflammation and insulin resistance in T2D. First, we will describe the physiological and pathological changes in AT that lead to inflammation and insu- lin resistance. We will next focus on the transcriptional and metabolic mechanisms described that

Similar to skeletal muscle, glucose utilization in adipose tissue also affects whole body glucose disposal. Following DEX treatment, a GR-dependent and transcription-independent mechanism that attenuates insulin signal has been identified recently in cultured adipocytes (107). The decreased insulin sensitivity was attributed to postreceptor signaling defects (156). Thus, incubation with DEX significantly inhibits total mRNA and tyrosine phosphorylation of IRS-1 (156, 181). The decreased IRS-1 reduces activation of phosphatidylinositol 3-kinase (PI 3-kinase), which plays a key role in the regulation of GLUT4 transport (156). Although the total amount of GLUT4 protein in 3T3-L1 adipocytes was unchanged, basal and insulin-induced transport of GLUT4 decreased following DEX (156). Total GLUT1 protein decreased in this experiment (156). Interestingly, even though IRS-1 and PI 3-kinase were normalized via IRS-1 overexpression, insulin-induced impairment of glucose uptake by DEX did not significantly ...

Many landmark studies have reported the Nod-like receptor proteins containing Pyrin domain (NLRP3) inflammasome activation in metabolic diseases that include obesity, atherosclerosis and type 2 diabetes. Therefore, the present study was aimed: (i) to determine the role of NLRP3 in inflammation and insulin resistance in high fat diet-induced obesity (DIO) model of mice, and (ii) to determine whether parthenolide, a NLRP3 inhibitor, is able to protect mice against inflammation and insulin resistance in high fat DIO model.. METHODS: Lipopolysaccharide (1 ng/ml) primed mouse intraperitoneal macrophages were treated with Parthenolide (0.1 to 30 μM) to evaluate its effect on TNF-α and IL-1β. Parthenolide and Pioglitazone were administered to DIO mice (fed 60% high fat diet) at 5 and 30 mg/kg QD, PO, respectively for 60 days to evaluate their effect on insulin resistance.. RESULTS: Parthenolide (5 mg/kg) markedly attenuated inflammatory cytokines as evidenced by significant and dose dependant ...

We found in a community-based cohort that insulin resistance, based on HOMA-IR, was associated with an increased risk of incident HF among those without diabetes at baseline. This risk appeared to occur at lower levels than the previously-defined insulin resistance threshold of a HOMA-IR of 2.5 and was not modified by race or BMI, but the relationship between insulin resistance and HF was stronger in younger participants, in females, and in those with lower baseline risk of HF. However, the association between insulin resistance and HF was no longer significant at HOMA-IR levels ≥2.5. Interim MI did not mediate the association between insulin resistance and HF.. The relationship between insulin resistance and incident HF has varied in prior studies. Our findings of a significant association between HOMA-IR, modeled flexibly with the use of cubic splines, and incident HF following adjustment for risk factors for HF corroborate a recent analysis of the Cardiovascular Health Study, which also ...

CONTEXT: The etiological mechanism of bile acid (BA) effects on insulin resistance and obesity is unknown. OBJECTIVE: To determine if plasma BA are elevated in human obesity and/or insulin resistance. DESIGN: Observational study. SETTING: Academic research center. PARTICIPANTS: 71 adult volunteers formed four groups: lean insulin-sensitive (BMI|/=25kg/m 2, HOMA-IR|2.0, n=19), overweight/obese non-diabetic who were either insulin-sensitive (Obsensitive, BMI|25kg/m 2, HOMA-IR|1.5, n=11), or insulin-resistant (Obresistant, BMI|25kg/m 2, HOMA-IR|3.0, n=20), and type 2 diabetes (T2D, n=21). MAIN OUTCOME MEASURES: Insulin sensitivity by hyperinsulinemic-euglycemic clamp, body composition by dual energy x-ray absorptiometry, abdominal fat distribution and liver density by CT and plasma BA. RESULTS: In the Obresistant group, glucose infusion rate/fat free mass (GIR/FFM, an inverse measure of insulin resistance) was significantly lower, and visceral and liver fat higher, compared to lean and Obsensitive subjects

Insulin resistance is defined as a disturbed metabolic response to exogenous or endogenous insulin. Insulin resistance results in increased insulin levels in blood plasma compared to those required for the available level of glucose. Chronic heart failure is currently one of the most severe and prognostically unfavorable cardiovascular diseases. Chronic heart failure is a progressive syndrome, and patients with asymptomatic CHF may proceed to a group of the most severely ill non-responders within 1-5 years. Insulin resistance may be present in CHF both as minimal changes (predisposition to hypo- or hyperglycemia; flattened glycemic curve) and as impaired resting glucose tolerance or DM. At present time, there is no unambiguous opinion on the correction of insulin resistance syndrome in patients with CHF. Considering the growing population of patients with DM and CHF, there is a need for a special (desirably randomized) trial to define an optimal antidiabetic therapy for patients with CHF and ...

Tumour necrosis factor alpha (TNF-α), acting as a modulator of gene expression in adipocytes, has been linked to the development of insulin resistance and obesity. The aim of this study was to investigate whether the A/G variation at position −308 in the TNFα promoter influences the body weight, insulin resistance, and postprandial lipaemia in Polish Caucasians. One hundred twenty one subjects, 38 men and 83 women, representing 40 obese families, were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). TNF-1 (GG) and TNF-2 (GA and AA) allele carriers were compared with respect to body mass index, fat/lean body mass composition, waist-to-hip ratio, as well as fasting lipids, glucose, leptin, and insulin fasting, and during the oral glucose tolerance test (4 points within 2 hours) and oral lipid tolerance test (OLTT; 5 points within 8 hours). The insulin sensitivity indices HOMA-IR (homeostasis model assessment of insulin resistance), ISI-COMP (whole ...

Prevalence of type 2 diabetes mellitus (T2DM) is increasing worldwide. To reduce its risk and progression, preventive strategies are needed. Vitamin supplementation such as vitamin D is one of the strategies. This study was designed to investigate the effect of injection of vitamin D on insulin resistance and anthropometric parameters in T2DM. This randomized double-blind clinical trial was conducted with 42 diabetic patients in two groups; intervention group with single intramuscular injection of 300,000 International Unit (IU) of vitamin D3 and the placebo group. After recording demographic and anthropometric factors (waist circumference, blood pressure and body mass index), fasting blood samples was taken for measurement of blood glucose, 25-hydroxyvitamin D3 (25-OHD3), insulin, glycosylated hemoglobin A1c (HbA1c) and estimation of Homeostasis Model Assessment Index (HOMA) in two times; before study and after three months. Two groups had similar baseline characteristics (each group = 21 subjects).

One study from China by Chen et al.[2] claimed that viral clearance is delayed by diabetes, hypertension, male gender (perhaps because the gene for ACE2 is on the X chromosome), and old age, which may worsen the prognosis of COVID-19 infection, likely due to the increased expression of ACE2. The authors recommended that the use of ACE inhibitors be carefully considered in such populations, as it may lead to upregulation of ACE2. However, there is another school of thought that ACE2 overexpression may help as it converts angiotensin-2 into angiotensin 1-7, which has effects exactly opposite to that of angiotensin-2, meaning that it can balance angiotensin-2 in the body so that it is potentially useful to protect against ARDS and the cytokine storm.[2] Therefore, ACE 2 seems to attract the virus into the pneumocytes, but on the contrary, perhaps also equips the cells against a cytokine storm. Thus, some authors have contended that blockage of the renin-angiotensin-aldosterone system (RAAS) by ACE ...

TY - JOUR. T1 - Unique Metabolic Features of Adults Discordant for Indices of Insulin Resistance. AU - Song, Yilin. AU - Søndergaard, Esben. AU - Jensen, Michael D.. N1 - Funding Information: Financial Support: This work was supported by the National. PY - 2020/6/9. Y1 - 2020/6/9. N2 - Purpose: Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) and Adipose Insulin Resistance index (ADIPO-IR) values are often concordant. In this study we evaluated whether there are groups discordant for HOMA-IR and ADIPOpalmitate-IR and, if so, what are their defining characteristics. Methods: The body composition, basal metabolic rate (BMR), fasting plasma lipids, insulin, glucose, and free fatty acid (FFA) palmitate concentrations data of 466 volunteers from previous research studies were abstracted and analyzed. The middle 2 population quartiles for HOMA-IR and Adipose Insulin Resistance index palmitate concentration (ADIPOpalmitate-IR) defined medium HOMA-IR and ADIPOpalmitate-IR (MH and MA), the ...

Pigment epithelium-derived factor (PEDF) is an anti-angiogenic, immunomodulatory, and neurotrophic serine protease inhibitor protein. PEDF is evolving as a novel metabolic regulatory protein that plays a causal role in insulin resistance. Insulin resistance is the central pathogenesis of metabolic disorders such as obesity, type 2 diabetes mellitus, polycystic ovarian disease, and metabolic syndrome, and PEDF is associated with them. The current evidence suggests that PEDF administration to animals induces insulin resistance, whereas neutralisation improves insulin sensitivity. Inflammation, lipolytic free fatty acid mobilisation, and mitochondrial dysfunction are the proposed mechanism of PEDF-mediated insulin resistance. This review summarises the probable mechanisms adopted by PEDF to induce insulin resistance, and identifies PEDF as a potential therapeutic target in ameliorating insulin resistance.. ...

The intestinal immune system is emerging as an important contributor to obesity-related insulin resistance, but the role of intestinal B cells in this context is unclear. Here, we show that high fat diet (HFD) feeding alters intestinal IgA+ immune cells and that IgA is a critical immune regulator of glucose homeostasis. Obese mice have fewer IgA+ immune cells and less secretory IgA and IgA-promoting immune mediators. HFD-fed IgA-deficient mice have dysfunctional glucose metabolism, a phenotype that can be recapitulated by adoptive transfer of intestinal-associated pan-B cells. Mechanistically, IgA is a crucial link that controls intestinal and adipose tissue inflammation, intestinal permeability, microbial encroachment and the composition of the intestinal microbiome during HFD. Current glucose-lowering therapies, including metformin, affect intestinal-related IgA+ B cell populations in mice, while bariatric surgery regimen alters the level of fecal secretory IgA in humans. These findings identify

New study finds the mechanism for insulin resistance leading to type 2 diabetes. Earlier work by Joshua Knowles, MD, PhD, an assistant professor of cardiovascular medicine at Stanford, and his team showed the connection of a human gene, NAT2, variant with insulin resistance in humans. The fact that type 2 diabetes was caused by insulin resistance was known to researchers for decades. However, the cause for this phenomenon was a mystery. Insulin, a hormone secreted by the pancreas, helps fat and muscle cells take up glucose from the blood. Insulin resistance is caused when human cells dont respond to insulin, resulting in the build up of glucose in the blood and subsequently leading to the production of even more insulin. Weve identified a mechanism for insulin resistance that involves a gene that ties insulin resistance to mitochondrial function, said Knowles. Scientists at the Stanford University School of Medicine and the University of Wisconsin have begun to find the connections between ...

Chronic heart failure (CHF) is associated with marked insulin resistance, characterized by both fasting and stimulated hyperinsulinemia. Furthermore, insulin resistance is a predictor of CHF and associated with more severe disease and a worse prognosis in patients with CHF. In CHF patients, therefore, insulin resistance is not merely a function of adiposity and may have implications in the pathophysiology of CHF disease progression. Angiotensin II negatively modulates insulin-mediated actions by regulating multiple levels of the insulin signaling cascade such as the insulin receptor, IRS, and PI3-kinase. Furthermore, both ACE inhibitors and angiotensin II receptor blockers (ARB) improve glycemic status not only in patients with type II diabetes but also in patients with hypertension and the metabolic syndrome. On the other hand, it is well known that some cytokines, such as TNF-α, are involved with pathophysiology of insulin resistance and CHF. However, it is still unclear whether the ARB ...

To our knowledge, this study is the first to show that a major protein-bound uremic toxin, PCS, induces insulin resistance in vivo in mice (Figure 2), as well as in vitro in C2C12 myotubes (Figure 6). The disruption of insulin signaling associated with CKD was described in 1955,32 and the effects of kidney disease on renal uptake and excretion of insulin were reported in 1970.33 Insulin resistance in CKD was evidenced by DeFronzo et al.17 using the gold standard euglycemic hyperinsulinemic clamp technique. In CKD, the decline of renal function is associated with the development of insulin resistance, and insulin resistance is recognized as an independent risk factor for cardiovascular morbidity and mortality in patients with CKD.19 However, the exact causes of insulin resistance in CKD are still poorly defined.20,22,23,34,35 McCaleb et al.36 demonstrated that isolated rat adipocytes had inhibition of insulin-stimulated glucose uptake after incubation with serum from patients with CKD, whereas ...

Obesity has reached epidemic proportions, but little is known about its influence on the intestinal immune system. Here we show that the gut immune system is altered during high-fat diet (HFD) feeding and is a functional regulator of obesity-related insulin resistance (IR) that can be exploited ther …

The effects of salicylates on insulin resistance. There is significant overlap between the intracellular events induced by TGs (or FFAs) and TNF regarding the mechanisms of insulin resistance. Both stimuli activate IKK-β and decrease insulin-induced tyrosine phosphorylation of IRS-1; both increase intracellular ceramide concentrations, which leads to inhibition of Akt/protein kinase B activation and inhibition of GLUT-4 translocation. These effects induce a state of insulin resistance. The effects of salicylate compounds on these pathways may be divergent. That is, they may improve insulin resistance by blocking the activation of IKK-β (top), or they may worsen insulin resistance by inhibiting PG synthesis and thus potentiating TNF release (bottom). In addition, inhibition of PG will decrease synthesis of leptin, which is known to improve insulin sensitivity by stimulating IRS-1-associated PI 3-kinase activity. The beneficial effect of leptin on insulin action is thus decreased (bottom ...

Insulin resistance is associated with increased circulating lipids and skeletal muscle lipid content. Chronic nicotinic acid (NA) treatment reduces insulin sensitivity and provides a model of insulin resistance. We hypothesized that the reduction in insulin sensitivity occurs via elevation of circulating nonesterified fatty acids (NEFAs) and an increase in intramyocellular lipid (IMCL). A total of 15 nondiabetic males (mean age 27.4 +/- 1.6 years) were treated with NA (500 mg daily for 1 week, 1 g daily for 1 week). Insulin sensitivity (glucose infusion rate [GIR]) was determined pre- and post-NA by euglycemic-hyperinsulinemic clamp. Substrate oxidation was determined by indirect calorimetry. Skeletal muscle lipid was assessed by estimation of long-chain acyl-CoA (LCACoA) and triglyceride (TG) content and by (1)H-magnetic resonance spectroscopy quantification of IMCL (n = 11). NA reduced GIR (P =.03) and nonoxidative glucose disposal (P ,.01) and increased fasting NEFAs (P =.01). The decrease in ...

Insulin resistance usually occurs early in the development of type 2 diabetes. An altered balance in the autonomic nervous system and in certain endocrine and inflammatory pathways, might contribute to the development of insulin resistance. In diabetes, hyperglycemia further aggravates insulin resistance as well as beta cell dysfunction but the mechanisms causing this phenomenon, i.e. glucotoxicity, are not fully understood.. Insulin resistance can be demonstrated in healthy first-degree relatives of type 2 diabetes patients who also have a high risk of developing type 2 diabetes. Relatives and control subjects without family history of diabetes were studied with respect to insulin sensitivity and the activity in the autonomic nervous system (ANS) and in the cortisol axis. Levels of sex hormones, leptin and cytokines were analysed. Abdominal adipose tissue distribution was determined with computed tomography.. Male relatives had decreased testosterone levels and increased leptin levels. There ...

Insulin resistance is a condition in which body cells do not fully respond to the action of insulin, a hormone that controls the amount of sugar (glucose) in the blood. As a result, blood sugar levels become abnormally high.. Over time, insulin resistance can result in consistently high blood sugar levels, which increases a persons risk for type 2 diabetes. Pregnant women who are insulin resistant have an increased risk for gestational diabetes.. Usually, insulin resistance develops in people who are overweight and not physically active. These characteristics are often associated with having high cholesterol and high blood pressure. People who are insulin resistant have an increased risk of heart disease and stroke, especially if other risk factors, such as being a smoker or having high cholesterol levels, are present. ...

A progressive decline in circulating androgens was observed with advancing age. Patients 21-30 years old had lower plasma glucose and insulin levels, lower area under the oral glucose tolerance test curve and lower homeostasis model assessment of insulin resistance index, and higher glucose/insulin and quantitative insulin sensitivity check index than patients 31-39 years old. The prevalence of PCOS phenotypes changed with age. More specifically, the distribution of the phenotypes did not differ substantially between patients ≤20 years old and patients 21-30 years old. However, a decline in the prevalence of phenotype 1 (characterized by anovulation, hyperandrogenemia, and polycystic ovaries) and an increase in the prevalence of phenotype 4 (characterized by anovulation and polycystic ovaries without hyperandrogenemia) were observed in patients 31-39 years old.. Conclusion(s): ...

Insulin resistance is a common finding in hypertensive humans and animal models. The Dahl salt-sensitive (S) rat is an ideal model of genetically predetermined insulin resistance and salt-sensitive hypertension. Along the insulin signaling pathway, the insulin receptor substrates 1 and 2 (IRS-1 and -2) are important mediators of insulin signaling. IRS-1 and/or IRS-2 genetic variant(s) and/or enhanced serine phosphorylation correlate with insulin resistance. The present commentary was designed to highlight the significance of IRS-1 and/or -2 in the pathogenesis of insulin resistance. An emphasis will be given to the putative role of IRS-1 and/or -2 genetic variant(s) and serine phosphorylation in precipitating insulin resistance.. ...

NAM Publications HIV & AIDS Information :: Diabetes. Insulin resistance is seen in Syndrome X a metabolic disorder with similar symptoms to HAART-associated lipodystrophy that occurs in HIV-negative people. Syndrome X may be corrected in some cases by the restoration of insulin sensitivity, using an anti-diabetes drug called metformin.. There is now evidence that metformin may be effective in reducing insulin resistance and abdominal fat in HIV-infected people on HAART. French doctors reported that metformin reduced insulin resistance, reduced triglyceride levels and improved abdominal fat distribution in a randomised study of 25 people receiving PIs.1 HIV wasting expert, Dr Carl Grunfeld, has also reported that metformin has shown the best results in the treatment of HAART-associated insulin resistance and diabetes, producing an associated decrease in body fat.. There is also evidence from randomised, controlled studies which suggests metformin is an effective treatment for insulin resistance ...

Fingerprint Dive into the research topics of Effect of vitamin D3 supplementation on insulin resistance and β-cell function in prediabetes: a double-blind, randomized, placebo-controlled trial. Together they form a unique fingerprint. ...

What is most interesting about our recent study is that it supports the idea that increasing fat breakdown may decrease insulin resistance in muscle, said Dr. Zwetsloot. Its exciting to be part of research that gives us a better understanding of insulin resistance, and that may result in new ways to prevent and treat the condition, especially if it advocates exercise.. The jury is still out, but decades of metabolic research suggests that exercising at a moderate pace for longer periods more effectively burns fat than short, intensive exercise.. Zwetsloots studies used either exercise or an anti-diabetic medication to decrease insulin resistance. In both cases, the treatments also caused an increase in fat breakdown. The studies acknowledge that more work needs to be done to fully understand insulin resistance, but suggest that increasing fat use as an energy source (such as by exercising) may help to alleviate insulin resistance. Zwetsloot, who earned her Ph.D. in bioenergetics at East ...

Increased adiposity and unhealthy lifestyle augment the risk for type 2 diabetes in children with familial predisposition. Insulin resistance (IR) is an excellent clinical marker for identifying children at high risk for type 2 diabetes. This study was conducted to investigate parental, physiological, behavioral and socio-economic factors related to IR in Korean children. This study is a cross-sectional study using data from 111 children aged 7 years and their parents. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated using fasting glucose and insulin level as a marker of IR. All childrens adiposity indices (r = 0.309-0.318, all P-value = 0.001) and maternal levels of fasting insulin (r = 0.285, P-value = 0.003) and HOMA-IR (r = 0.290, P-value = 0.002) were positively correlated with childrens HOMA-IR level. There was no statistical difference of childrens HOMA-IR level according to childrens lifestyle habits and socioeconomic status of families. An increase of 1 percentage

Increased adiposity and unhealthy lifestyle augment the risk for type 2 diabetes in children with familial predisposition. Insulin resistance (IR) is an excellent clinical marker for identifying children at high risk for type 2 diabetes. This study was conducted to investigate parental, physiological, behavioral and socio-economic factors related to IR in Korean children. This study is a cross-sectional study using data from 111 children aged 7 years and their parents. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated using fasting glucose and insulin level as a marker of IR. All childrens adiposity indices (r = 0.309-0.318, all P-value = 0.001) and maternal levels of fasting insulin (r = 0.285, P-value = 0.003) and HOMA-IR (r = 0.290, P-value = 0.002) were positively correlated with childrens HOMA-IR level. There was no statistical difference of childrens HOMA-IR level according to childrens lifestyle habits and socioeconomic status of families. An increase of 1 percentage

TY - JOUR. T1 - Targeting BCAA catabolism to treat obesity-associated insulin resistance. AU - Zhou, Meiyi. AU - Shao, Jing. AU - Wu, Cheng Yang. AU - Shu, Le. AU - Dong, Weibing. AU - Liu, Yunxia. AU - Chen, Mengping. AU - Wynn, R. Max. AU - Wang, Jiqiu. AU - Wang, Ji. AU - Gui, Wen Jun. AU - Qi, Xiangbing. AU - Lusis, Aldons J.. AU - Li, Zhaoping. AU - Wang, Weiqing. AU - Ning, Guang. AU - Yang, Xia. AU - Chuang, David T.. AU - Wang, Yibin. AU - Sun, Haipeng. N1 - Funding Information: Funding. This work was supported by the Ministry of Science and Technology of China (grant nos. 2012BAI02B05 and 2013YQ030923), the National International Science Cooperation Foundation (grant no. 2015DFA30560), the National Natural Science Foundation of China (grant nos. NSFC81570717 and 81522011), the National Institutes of Health (grant nos. HL108186, HL103205, HL098954, and DK62306), the National Heart, Lung, and Blood Institute (grant no. HL080111), the Laubisch Fund (to the University of California Los ...

Type 2 diabetes is usually preceded by a long and clinically silent period of increasing insulin resistance. The purpose of this study is to demonstrate that rosiglitazone and metformin fixed-dose combination therapy (RSG/MET) will safely and effectively control glycemia as a first line of oral therapy, better than rosiglitazone (RSG) or metformin (MET) monotherapy in Korean type 2 diabetes patients. METHODS: This study was a 32-week, multicenter, randomized, double-blind study. Twenty-seven type 2 diabetes patients (males 14; females 13) were included and randomly divided into the rosiglitazone, metformin group, or rosiglitazone /metformin combination groups. The primary objective of this study was to determine the change in HbA1c from baseline (week 0) to week 32. The secondary end-points were to determine changes in fasting plasma glucose (FPG) and homeostasis model assessment insulin resistance (HOMA-IR), from baseline to week 32. Other cardiovascular risk markers were also assessed. ...

TY - JOUR. T1 - High serum resistin is associated with an increase in adiposity but not a worsening of insulin resistance in Pima Indians. AU - de Courten, Barbora. AU - Considine, Robert V. AU - Degawa-Yamauchi, Mikako. AU - Tataranni, P Antonio. PY - 2004/5/1. Y1 - 2004/5/1. N2 - Resistin is an adipokine with putative prodiabetogenic properties. Like other hormones secreted by adipose tissue, resistin is being investigated as a possible etiologic link between excessive adiposity and insulin resistance. Although there is growing evidence that circulating levels of this adipokine are proportional to the degree of adiposity, an effect on insulin resistance in humans remains unproven. To evaluate the relations among resistin, obesity, and insulin resistance, we measured fasting serum resistin levels in 113 nondiabetic (75-g oral glucose tolerance test) Pima Indians (ages 29 ± 7 years, body fat 31 ± 8%, resistin 3.7 ± 1.1 ng/ml [means ± SD]), who were characterized for body composition ...

TNF-α is an inflammatory cytokine that plays an important role in insulin resistance observed in obesity and chronic inflammation. Many cellular components involved in insulin signaling cascade are known to be inhibited by TNF-α. Insulin receptor substrate (IRS)-1 is one of the major targets in TNF-α-induced insulin resistance. The serine phosphorylation of IRS-1 enables the inhibition of insulin signaling. Until now, many studies have been conducted to investigate the mechanism of TNF-α-induced insulin resistance based on Western blot. Intracellular protein kinase crosstalk is commonly encountered in inflammation-associated insulin resistance. The crosstalk among the signaling molecules obscures the precise role of kinases in insulin resistance. We have developed a cell lysis-free quantum dots (QDots) multicolor cellular imaging to identify the biochemical role of multiple kinases (p38, JNK, IKKβ, IRS1ser, IRS1tyr, GSK3β, and FOXO1) in inflammation-associated insulin resistance pathway with a

ENGLISH ABSTRACT: Background: The aetiopathogenesis of type 2 diabetes and the associated insulin resistance have been shown to have a strong genetic basis. Several genetic variants of the peroxisome proliferatoractivated receptor gamma (PPARG) and the insulin receptor substrate (IRS) 1 genes have been associated with the metabolic states of obesity, insulin resistance and type 2 diabetes in Caucasian populations. Furthermore, insulin resistance is strongly associated with diabetes and subsequent cardiovascular disease. These are increasingly common in low- to middle -income countries, including South Africa. Limited information is currently available regarding genetic associations with insulin resistance in African populations. Objectives: (1) To identify subjects with insulin resistance and determine the frequencies of the single nucleotide polymorphisms in the PPARG and IRS1 genes and examine the associated risk of insulin resistance and type 2 diabetes mellitus in a mixed-ancestry South ...

TY - JOUR. T1 - Clinical evaluation of insulin resistance and β-cell function by the homeostasis model assessment in patients with systemic lupus erythematosus. AU - Tso, Tim K.. AU - Huang, Hui Yu. AU - Chang, Chen Kang. AU - Huang, Wen Nan. AU - Liao, Ying Ju. PY - 2004/10/1. Y1 - 2004/10/1. N2 - The aim of this preliminary study was to evaluate insulin resistance and secretion using homeostasis model assessment (HOMA) in patients with systemic lupus erythematosus (SLE). The fasting glucose and insulin concentrations, HOMA insulin resistance (IR), HOMA β-cell, antidouble-stranded DNA antibodies (anti-dsDNA), C3, C4, and SLE disease activity index (SLEDAI) were determined in a total of 58 female SLE patients. All patients were classified into subgroups according to the presence of anticardiolipin antibodies (aCL + vs. aCL-) and SLEDAI scores (SLEDAI , 3 vs. SLEDAI , 3). Results showed that SLE patients with and without aCL had significantly higher fasting insulin levels, HOMA IR, and HOMA ...

TY - JOUR. T1 - Perturbation of glucose flux in the liver by decreasing F26P2 levels causes hepatic insulin resistance and hyperglycemia. AU - Wu, Chaodong. AU - Khan, Salmaan A.. AU - Peng, Li Jen. AU - Li, Honggui. AU - Carmella, Steven G.. AU - Lange, Alex J.. N1 - Copyright: Copyright 2008 Elsevier B.V., All rights reserved.. PY - 2006. Y1 - 2006. N2 - Hepatic insulin resistance is one of the characteristics of type 2 diabetes and contributes to the development of hyperglycemia. How changes in hepatic glucose flux lead to insulin resistance is not clearly defined. We determined the effects of decreasing the levels of hepatic fructose 2,6-bisphosphate (F26P2), a key regulator of glucose metabolism, on hepatic glucose flux in the normal 129J mice. Upon adenoviral overexpression of a kinase activity-deficient 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase, the enzyme that determines F26P2 level, hepatic F26P2 levels were decreased twofold compared with those of control virus-treated mice ...

Background and aim: Acanthosis nigricans (AN) is characterized by hyperpigmented velvety plaques of body folds and neck. Insulin can have a role in the pathogenesis of this disease and hyperinsulinemia as a consequence of insulin resistance may stimulate the formation of the characteristic plaques of AN. In this study insulin resistance was compared in obese women with and without AN.Materials and Methods: Glucose tolerance test (GTT) and fasting blood insulin were measured in two groups of obese women (BMI|30 kg/m2) with AN (32 cases) and without AN (34 cases) and insulin resistance was determined using HOMA formula.Results: The mean fasting blood insulin in two groups with and without AN were 15.5±8.5 and 12.2±4.1 IU/mL; respectively (P|0.05). The mean of insulin resistance in two groups with and without AN were 3.5±1.9 and 2.6±0.9; respectively (P|0.05). The results of GTT showed that the mean fasting blood sugar was 89.5±12 mg/dl and following using glucose were 144±7 mg/dl after 30 minutes,

TY - JOUR. T1 - Proinsulin-to-C-peptide ratio versus proinsulin-to-insulin ratio in the prediction of incident diabetes. T2 - The Insulin Resistance Atherosclerosis Study (IRAS). AU - Loopstra-Masters, R. C.. AU - Haffner, S. M.. AU - Lorenzo, C.. AU - Wagenknecht, L. E.. AU - Hanley, A. J.. PY - 2011/12/1. Y1 - 2011/12/1. N2 - Aims: Associations of proinsulin-to-insulin ratios with incident type 2 diabetes have been inconsistent. The use of C-peptide as the denominator in the ratio may allow for better prediction because C-peptide concentration is not affected by hepatic insulin clearance. The objective of this paper was to compare fasting intact and split proinsulin-to-insulin ratios (PI/I, SPI/I) with intact and split proinsulin-to-C-peptide ratios (PI/C-pep, SPI/C-pep) in the prediction of type 2 diabetes. Methods: Prospective data on 818 multi-ethnic adults without diabetes at baseline from the Insulin Resistance Atherosclerosis Study (IRAS) were used. Insulin sensitivity (S I) and acute ...

TY - JOUR. T1 - 12/15-Lipoxygenase is equired for the early onset of high fat diet-induced adipose tissue inflammation and insulin resistance in mice. AU - Sears, Dorothy D.. AU - Miles, Philip D.. AU - Chapman, Justin. AU - Ofrecio, Jachelle M.. AU - Almazan, Felicidad. AU - Thapar, Divya. AU - Miller, Yury I.. PY - 2009/9/29. Y1 - 2009/9/29. N2 - Background: Recent understanding that insulin resistance is an inflammatory condition necessitates searching for genes that regulate inflammation in insulin sensitive tissues. 12/15-lipoxygenase (12/15LO) regulates the expression of proinflammatory cytokines and chemokines and is implicated in the early development of diet-induced atherosclerosis. Thus, we tested the hypothesis that 12/15LO is involved in the onset of high fat diet (HFD)-induced insulin resistance. Methodology/Principal Findings: Cells over-expressing 12/15LO secreted two potent chemokines, MCP-1 and osteopontin, implicated in the development of insulin resistance. We assessed adipose ...

TY - JOUR. T1 - Elevated Fibroblast growth factor 21 (FGF21) in obese, insulin resistant states is normalised by the synthetic retinoid Fenretinide in mice. AU - Morrice, Nicola. AU - Mcilroy, George D.. AU - Tammireddy, Seshu R.. AU - Reekie, Jennifer. AU - Shearer, Kirsty D.. AU - Doherty, Mary K.. AU - Delibegovi??, Mirela. AU - Whitfield, Phillip D.. AU - Mody, Nimesh. PY - 2017/3/3. Y1 - 2017/3/3. N2 - Fibroblast growth factor 21 (FGF21) has emerged as an important beneficial regulator of glucose and lipid homeostasis but its levels are also abnormally increased in insulin-resistant states in rodents and humans. The synthetic retinoid Fenretinide inhibits obesity and improves glucose homeostasis in mice and has pleotropic effects on cellular pathways. To identify Fenretinide target genes, we performed unbiased RNA-seq analysis in liver from mice fed high-fat diet ± Fenretinide. Strikingly, Fgf21 was the most downregulated hepatic gene. Fenretinide normalised elevated levels of FGF21 in ...

BACKGROUND: Obesity is a strong risk factor for resistance to insulin-mediated glucose disposal, a precursor of type 2 diabetes and other disorders. However, not all obese individuals are insulin resistant. We sought to identify the molecular pathways that might cause obesity-associated insulin resistance in humans by studying the morbidly obese who were insulin sensitive versus insulin resistant, thereby eliminating obesity as a variable. METHODS: Combining gene expression profiling with computational approaches, we determined the global gene expression signatures of omental and subcutaneous adipose tissue samples obtained from similarly obese patients undergoing gastric bypass surgery. RESULTS: Gene sets related to chemokine activity and chemokine receptor binding were identified as most highly expressed in the omental tissue from insulin-resistant compared with insulin-sensitive subjects, independent of the body mass index. These upregulated genes included chemokines (C-C motif) ligand 2, 3, 4, and

Approximately 50% to 70% of women with polycystic ovary syndrome (PCOS) have some degree of insulin resistance, and obesity is known to worsen insulin resistance. According to the study by the Ewha Womans University School of Medicine, posted in PubMed, ISI was significantly lower in both lean and ow/ob women with PCOS compared to BMI-matched controls (p,0.05). Increasing BMI by 1 kg/m(2) decreased ISI by 0.169 in PCOS patients (p,0.05) and by 0.238 in controls (p,0.05); there was no significant difference between these groups. In lean PCOS patients and lean controls, BMI had no effect on ISI. Multiple regression analysis revealed that PCOS status (β=-0.423, p,0.001) and BMI (β=-0.375, p,0.001) were significantly associated with ISI. Conclusion: Insulin resistance is an intrinsic defect of PCOS, and a high BMI could exacerbate insulin resistance in all women, irrespective of whether they have PCOS. ...

Blueberries are a rich source of polyphenols, which include anthocyanin bioactive compounds. Epidemiological evidence indicates that incorporating blueberries into the diet may lower the risk of developing type 2 diabetes (T2DM). These findings are supported by pre-clinical and clinical studies that have shown improvements in insulin resistance (i.e., increased insulin sensitivity) after obese and insulin-resistant rodents or humans consumed blueberries. Insulin resistance was assessed by homeostatic model assessment-estimated insulin resistance (HOMA-IR), insulin tolerance tests, and hyperinsulinemic-euglycemic clamps. Additionally, the improvements in glucose tolerance after blueberry consumption were assessed by glucose tolerance tests. However, firm conclusions regarding the anti-diabetic effect of blueberries cannot be drawn due to the small number of existing clinical studies. Although the current evidence is promising, more long-term, randomized, and placebo-controlled trials are needed to

Our cross-sectional analysis indicated a positive association between plasma aldosterone levels and insulin resistance. However, this association may be an epiphenomenon. Accordingly, we hypothesized that high levels of plasma aldosterone could predict the development of insulin resistance. Our results confirmed the hypothesis in subjects without insulin resistance at baseline. Although a recent prospective study from the Framingham Offspring Study29 has demonstrated that higher aldosterone levels are associated with the development of metabolic syndrome, they failed to demonstrate the association of aldosterone with the development of insulin resistance. The reason was not clear, but they stated in their limitations that, for the calculation of HOMA-insulin resistance, they used glucose and insulin 4 years before the baseline examination. Another explanation may be the racial difference, including the demographic backgrounds of the subjects, such as the prevalence of obesity; mean BMI in the ...

Non-alcoholic fatty liver disease (NAFLD) may result from obesity accompanied by insulin resistance and adipose tissue inflammation or from the common genetic variants in PNPLA3 (rs738409, C,G/I148M), TM6SF2 (rs58542926, C,T/E167K) and MBOAT7 (rs641738, C,T). These variants increase the liver fat content and the severity of NAFLD without features of insulin resistance. This thesis aimed to determine the following: i) whether NAFLD predicts type 2 diabetes independent of obesity and other known risk factors; ii) whether adipose tissue is inflamed in subjects homozygous for the PNPLA3 I148M variant; iii) whether obesity and insulin resistance rather than liver fat content increase coagulation factor activities and expression; and iv) which factors predict NAFLD and liver stiffness during an 11-year follow-up period. The present thesis includes one systematic review, two cross-sectional studies and one longitudinal study. Study subjects comprised Finnish adult men and women. Liver fat content was ...

Acylcarnitine accumulation in skeletal muscle and plasma has been observed in numerous models of mitochondrial lipid overload and insulin resistance. Fish oil n3PUFA (omega-3 polyunsaturated fatty acids) are thought to protect against lipid-induced insulin resistance. The present study tested the hypothesis that the addition of n3PUFA to an intravenous lipid emulsion would limit muscle acylcarnitine accumulation and reduce the inhibitory effect of lipid overload on insulin action. On three occasions, six healthy young men underwent a 6-h euglycaemic-hyperinsulinaemic clamp accompanied by intravenous infusion of saline (Control), 10% Intralipid® [n6PUFA (omega-6 polyunsaturated fatty acids)] or 10% Intralipid®+10% Omegaven® (2:1; n3PUFA). The decline in insulin-stimulated whole-body glucose infusion rate, muscle PDCa (pyruvate dehydrogenase complex activation) and glycogen storage associated with n6PUFA compared with Control was prevented with n3PUFA. Muscle acetyl-CoA accumulation was greater ...

Acylcarnitine accumulation in skeletal muscle and plasma has been observed in numerous models of mitochondrial lipid overload and insulin resistance. Fish oil n3PUFA (omega-3 polyunsaturated fatty acids) are thought to protect against lipid-induced insulin resistance. The present study tested the hypothesis that the addition of n3PUFA to an intravenous lipid emulsion would limit muscle acylcarnitine accumulation and reduce the inhibitory effect of lipid overload on insulin action. On three occasions, six healthy young men underwent a 6-h euglycaemic-hyperinsulinaemic clamp accompanied by intravenous infusion of saline (Control), 10% Intralipid® [n6PUFA (omega-6 polyunsaturated fatty acids)] or 10% Intralipid®+10% Omegaven® (2:1; n3PUFA). The decline in insulin-stimulated whole-body glucose infusion rate, muscle PDCa (pyruvate dehydrogenase complex activation) and glycogen storage associated with n6PUFA compared with Control was prevented with n3PUFA. Muscle acetyl-CoA accumulation was greater ...

Polycystic ovarian syndrome is most common endocrine disease and metabolic disorder in adolescence and reproductive women. In PCOS women insulin resistance thought to be the uniting pathogenic factor in the development of glucose intolerance, obesity, lipid abnormalities, HTN and coronary artery disease .This study is under taken to measure insulin resistance in PCOS and to see the relationship of insulin resistance with serum lipoprotein ratio. Case control study was done taking 60 women PCOS and 60 age matched healthy women as controls.In all the subjects, concentrations of fasting plasma glucose, serum TG, serum TC and HDL were estimated using enzymatic methods in semiautoanalyser. Fasting serum insulin and was measured by CLIA using Lumax-CLIA microplate reader. HOMA IR, serum LDL concentration, serum TC:HDL ratio, serum TG:HDL ratio and serum LDL:HDL ratio were calculated from estimated parameters.The mean concentrations of all the parameters were significantly increased in women with

Under fasting conditions, increases in circulating concentrations of glucagon maintain glucose homeostasis via the induction of hepatic gluconeogenesis. Triggering of the cAMP pathway in hepatocytes stimulates the gluconeogenic program via the PKA-mediated phosphorylation of CREB and dephosphorylation of the cAMP regulated CREB coactivators CRTC2 and CRTC3. In parallel, decreases in circulating insulin also increase gluconeogenic gene expression via the de-phosphorylation and activation of the forkhead transcription factor FOXO1. Hepatic gluconeogenesis is increased in insulin resistance where it contributes to the attendant hyperglycemia. Whether selective activation of the hepatic CREB/CRTC pathway is sufficient to trigger metabolic changes in other tissues is unclear, however. Modest hepatic expression of a phosphorylation-defective and therefore constitutively active CRTC2S171,275A protein increased gluconeogenic gene expression under fasting as well as feeding conditions. Circulating ...

Objective: Acromegaly is a rare pituitary disease due to excessive secretion of GH. Insulin resistance, impaired glucose tolerance (IGT) and diabetes mellitus (DM) are common features in acromegaly. Seventy-four active acromegalic patients were retrospectively evaluated in order to determine the impact of family history for diabetes mellitus on glucose tolerance, insulin resistance and beta-cell function.. Patients and methods: We studied 74 patients with active acromegaly (mean IGF-1 value: 576.8±35.6 ng/ml ES; mean GH value on OGTT nadir 11.8±1.8 ng/ml ES), 29 males and 45 females, aged 50.4±14.1 years, body mass index (BMI) 28.1±4.3 (kg/m2). All patients underwent an oral glucose tolerance test (OGTT): GH, blood glucose and insulin were sampled at 0, 30, 60, 90, 120 minutes. Insulin resistance was evaluated with HOMA2-IR, Quicki and ISI0.120; beta cell function was evaluated with HOMA2%-ß index.. Results: Acromegalic patients with a positive family history for diabetes mellitus showed an ...

Rapid, clinical improvements in type 2 diabetes occur after RYGB (4,5), yet little is known regarding the relative contribution of insulin-sensitive tissues. To determine this, we measured hepatic and muscle insulin sensitivity with a hyperinsulinemic-euglycemic clamp. Our major finding was that at 1 month after RYGB, hepatic insulin sensitivity improved whereas skeletal muscle insulin sensitivity did not. In addition, hepatic and peripheral insulin sensitivity was not influenced by surgical removal of the omentum, as postoperative values were similar in the groups who did and did not undergo omentectomy. Lima et al. (13) reported that omentectomy did not affect peripheral insulin sensitivity at 1 month after RYGB, but they did not directly assess hepatic insulin sensitivity. We have previously reported that omentectomy does not influence metabolic outcomes of RYGB after long-term follow-up (8).. The rapid and sustained improvement in diabetes after RYGB has contributed to the American Diabetes ...

Podcast: Play in new window , Download. Subscribe: Apple Podcasts , Android , RSS. In episode 99 of the Real World Wellness podcast, Christine explains the critical role that insulin plays in lowering your glucose levels and how problems occur with insulin and lead to insulin resistance before you can detect prediabetes and type 2 diabetes. Since insulin resistance is associated with metabolic syndrome, PCOS, cancer, diabetes, and many other diseases, you want to get your insulin levels tested. Christine explains the risk factors for insulin resistance and what test to ask for. She also talks about the insulin index for food and beverages and what healthy foods produce a high insulin response and should be avoided.. Resources:. https://www.ncbi.nlm.nih.gov/pubmed/18936729. https://www.ncbi.nlm.nih.gov/pubmed/17259468. https://www.ncbi.nlm.nih.gov/pubmed/18096375?log$=activity. Next Episode: Christine will talk more about strategies to increase insulin sensitivity ranging from supplements to ...

The effect of thyroid status on insulin sensitivity is of great interest but despite various studies there is conflicting data on this subject. The study group comprised of 25 female subjects each with subclinical hypothyroidism, overt hypothyroidism and euthyroid controls. Serum samples of all the patients were assayed for thyroid profile, Insulin and lipid profile. Homeostasis model of assessment (HOMA-IR) was employed to assess the level of insulin resistance. Patients with hypothyroidism demonstrated insulin resistance and dyslipidemia as observed by the higher HOMA-IR and cholesterol and triglyceride levels respectively as compared to the controls. A significantly positive correlation between TSH and HOMA-IR level was also observed in the hypothyroidism group. Thyroid dysfunction leads to alterations in glucose and lipid metabolism which is an important risk factor for cardiovascular diseases. The dyslipidemia and insulin resistance should be managed aggressively to reduce the impending risk.

Compared to healthy individuals, those with stably repressed HIV experience a higher risk of developing insulin resistance, a hallmark of pre-diabetes and a major determinant for cardiometabolic diseases. Although epigenetic processes, including in particular DNA methylation, appear to be dysregulated in individuals with insulin resistance, little is known about where these occur in the genomes of immune cells and the origins of these alterations in HIV-infected individuals. Here, we examined the genome-wide DNA methylation states of monocytes in HIV-infected individuals (n = 37) with varying levels of insulin sensitivity measured by the homeostatic model assessment of insulin resistance (HOMA-IR). By profiling DNA methylation at single-nucleotide resolution using the Illumina Infinium HumanMethylation450 BeadChip in monocytes from insulin-resistant (IR; HOMA-IR ≥ 2.0; n = 14) and insulin-sensitive (IS; HOMA-IR | 2.0; n = 23) individuals, we identified 123 CpGs with significantly different DNA

|p|Cardiovascular risk of prediabetes is still subject to controversies. We analyzed the associations between insulin resistance, adipokines and incipient atherosclerosis estimated by intima-media thickness (IMT) in a cross-sectional study on 122 prediabetic subjects without clinical signs of atherosclerotic disease. Homeostasis model assessment of insulin resistance (HOMA-IR, calculated as fasting insulin × fasting plasma glucose / 22.5), adiponectin, leptin, leptin-to-adiponectin ratio, carotid and femoral IMT were evaluated. We also assessed other parameters related to insulin resistance and adipokines (HbA1c, anthropometric and lipid parameters), as they may also influence atherosclerosis. Carotid IMT was correlated to adiponectin and leptin-to-adiponectin ratio (all p < 0.05), but not with HOMA-IR or leptin, while femoral IMT showed no relationship with these factors. After adjusting for leptin, leptin-to-adiponectin ratio, triglycerides, HDL-cholesterol, cholesterol-to-HDL ratio, triglycerides

We are interested in how skeletal muscle processes fat and its effect on insulin resistance. This is an important question since insulin resistance predates and predicts type 2 diabetes. We know that if pharmaceutical grade lipid is infused into people, they develop insulin resistance. Thus, we would like to infuse pharmaceutical grade lipid into trained subjects, believing that trained subjects will develop less insulin resistance, less decline in muscle energy function, and less accumulation of fat metabolites than untrained subjects. For comparing the effects of the pharmaceutical grade fat infusion, we will also have a group of trained and untrained subjects given a control (glycerol) infusion. Glycerol is basically the same as pharmaceutical grade lipid infusion without the lipid component.. Three visits will be required. The first visit will involve measurement of fitness. A second visit will involve measurement of insulin resistance. The third visit will involve an inpatient stay, with a ...

Author(s): Hivert, Marie-France; Cardenas, Andres; Allard, Catherine; Doyon, Myriam; Powe, Camille E; Catalano, Patrick M; Perron, Patrice; Bouchard, Luigi | Abstract: The placenta participates in maternal insulin sensitivity changes during pregnancy; however, mechanisms remain unclear. We investigated associations between maternal insulin sensitivity and placental DNA methylation markers across the genome. We analyzed data from 430 mother-offspring dyads in the Gen3G cohort. All women underwent 75-g oral glucose tolerance tests at ∼26 weeks of gestation; we used glucose and insulin measures to estimate insulin sensitivity (Matsuda index). At delivery, we collected samples from placenta (fetal side) and measured DNA methylation using Illumina EPIC arrays. Using linear regression models to quantify associations at 720,077 cytosine-guanine dinucleotides (CpGs), with adjustment for maternal age, gravidity, smoking, BMI, child sex, and gestational age at delivery, we identified 188 CpG sites where

In the present study, we have directly demonstrated that overexpression of PKC-β2 in endothelial cells inhibits insulin signaling and insulin action and increases expression of ET-1, resulting in endothelial dysfunction and accelerated atherosclerosis. These findings may help explain the elevated risk for atherosclerosis in diabetic and insulin-resistant states because PKC activation, especially the β-isoform, has been shown to be induced by hyperglycemia or elevated free fatty acids in many vascular tissues.26 The inhibiting role of PKC-β on insulin activation of eNOS clearly has been shown in endothelial cells from diabetic patients.15 At the cell signaling level, the vasotropic effects of insulin, such as the activation of eNOS, induction of heme oxygenase-1 and vascular endothelial growth factor, and downregulation of VCAM-1, are mediated through activation of the IRS/PI3K/Akt pathway.6,27,28 PKC activation, especially β-isoform, has been shown to selectively inhibit this pathway by ...

TY - JOUR. T1 - Osthol attenuates hepatic steatosis via decreased triglyceride synthesis not by insulin resistance. AU - Nam, Ho Hyun. AU - Jung, Dae Won. AU - Jeon, Hye Joon. AU - Lee, Jai Sun. AU - Saeed, Waqar Khalid. AU - Kim, Eun Kyung. PY - 2014/9/7. Y1 - 2014/9/7. N2 - AIM: To evaluate the effects of osthol on intrahepatic fat synthesis, β-oxidation, inflammation, and insulin resistance by multifaceted analysis. METHODS: Sprague-Dawley rats (n = 30) were randomly divided into control, non-alcoholic fatty liver disease (NAFLD), and osthol groups. NAFLD and osthol groups were fed with a high-fat diet for 14 wk. After 8 wk of the high-fat diet, the osthol group also received osthol 20 mg/kg orally 5 times/wk. To assess the insulin resistance, oral glucose tolerance was performed at the end of 14 wk. Immunohistochemical (4-HNE, F4/80) and hematoxylin and eosin (HE) staining were performed on liver tissue extracts after animal sacrifice at 14 wk. SREBP1c, FAS, SCD-1, PPAR-α, CROT, MCP-1, ...

What is Insulin Resistance?. Under normal circumstances, insulin is tightly controlled by a natural homoeostatic feedback mechanism. With every meal, insulin is released as carbohydrates enter the blood stream. In a healthy body, the insulin receptors in the cell membranes respond to the hormone, and take up carbohydrates and other nutrients. This, in turn, reduces the production of insulin.. The problem starts when the tissue fails to respond to insulin. When this happens, the sugar in the blood remains high despite the presence of insulin, and the body has no choice but to release more insulin. It becomes a vicious cycle because it is actually the presence of insulin that makes the tissue more and more resistant to it.. This is how insulin exposure determines the rate of ageing: with every insulin release, cell membranes become a little bit more insulin resistant. A gradual increase in insulin concentration over time is normal, but the current epidemic of severe insulin resistance is a modern ...

TY - JOUR. T1 - Insulin sensitivity and regional fat gain in response to overfeeding. AU - Votruba, Susanne B.. AU - Jensen, Michael D.. PY - 2011/2. Y1 - 2011/2. N2 - Although insulin resistance and type 2 diabetes (T2DM) are associated with upper body fat distribution, it is unknown whether insulin resistance predisposes to upper body fat gain or whether upper body fat gain causes insulin resistance. Our objective was to determine whether insulin sensitivity predicts abdominal (subcutaneous and/or visceral) fat gain in normal weight adults. Twenty-eight (15 men) lean (BMI = 22.1 2.5kg/m2), healthy adults underwent ∼8 weeks of overfeeding to gain ∼4kg fat. Body composition was assessed before and after overfeeding, using dual-energy X-ray absorptiometry (DXA) and abdominal computed tomography to measure total and regional (visceral, abdominal, and lower body subcutaneous) fat gain. We assessed insulin sensitivity with an intravenous glucose tolerance test (IVGTT) and the 24-h insulin area ...

TY - JOUR. T1 - Low-grade inflammation and muscular fitness on insulin resistance in adolescents. T2 - Results from LabMed Physical Activity Study. AU - Agostinis-Sobrinho, César A.. AU - Ramírez-Vélez, Robinson. AU - García-Hermoso, Antonio. AU - Moreira, Carla. AU - Lopes, Luís. AU - Oliveira-Santos, José. AU - Abreu, Sandra. AU - Mota, Jorge. AU - Santos, Rute. PY - 2018/5/1. Y1 - 2018/5/1. N2 - Background: Low muscular fitness (MF) and low-grade inflammation has been linked to insulin resistance (IR). Objective: To evaluate the associations between MF and a clustered score of inflammatory biomarkers on IR and to investigate the combined impact of MF and inflammation on IR in adolescents. Methods: This is a cross-sectional analysis with 529 adolescents (267 girls) aged 12 to 18 years. Pubertal stage, socioeconomic status, adherence to the Mediterranean diet, cardiorespiratory fitness, and waist circumference were assessed. Standing long-jump and isometric handgrip dynamometry were used ...

Insulin resistance occurs in around 50% to 80% of women with PCOS [12], primarily in the more severe NIH diagnosed PCOS and in those who are overweight. Lean women [13] and milder Rotterdam diagnosed PCOS [14] appear to have less severe insulin resistance. A full discussion of the complex mechanisms involved in insulin resistance, hyperinsulinaemia, DM2 and CVD is beyond the scope of this review. Mechanisms involved in insulin resistance are likely to be complex with genetic and environmental contributors. Specific abnormalities of insulin metabolism identified in PCOS include reductions in secretion [39, 40], reduced hepatic extraction [40], impaired suppression of hepatic gluconeogenesis [41] and abnormalities in insulin receptor signalling [42]. Interestingly, there is a paradoxical expression of insulin resistance in PCOS whereby insulin-stimulated androgen production persists while its role in glucose metabolism is impaired [42]. Therefore, insulin resistance in PCOS results in ...

Polycystic ovary syndrome (PCOS) is associated with an increased risk of insulin resistance (IR), metabolic syndrome (MetS), impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM). Metabolic aspects of the four PCOS phenotypes remain to be fully defined. The aim of this study was to compare metabolic parameters and insulin resistance among the four PCOS phenotypes defined according to the Rotterdam criteria and to determine predictors of these complications. A total of 526 reproductive-aged women were included in this observational case-control study. Of these, 263 were diagnosed as a PCOS based on Rotterdam criteria and 263 infertile women with no evidence of PCOS were recruited as controls. Biochemical, metabolic and insulin resistance parameters were compared in the two groups and the frequency of MetS and IR were compared among the four phenotypes. Data were analyzed for statistical significance using Students t-test and one way analysis of variance followed by a post-hoc test (least

TY - JOUR. T1 - Dietary phosphate modulates atherogenesis and insulin resistance in apolipoprotein E knockout mice--brief report. AU - Ellam, Timothy. AU - Wilkie, Martin. AU - Chamberlain, Janet. AU - Crossman, David. AU - Eastell, Richard. AU - Francis, Sheila. AU - Chico, Timothy J A. PY - 2011/9. Y1 - 2011/9. N2 - Epidemiological studies link higher serum phosphate and the phosphatonin fibroblast growth factor 23 with cardiovascular events and atheroma, and they link lower serum phosphate with insulin resistance and the metabolic syndrome. We investigated whether manipulating dietary phosphate influences atherogenesis or insulin sensitivity in mice.. AB - Epidemiological studies link higher serum phosphate and the phosphatonin fibroblast growth factor 23 with cardiovascular events and atheroma, and they link lower serum phosphate with insulin resistance and the metabolic syndrome. We investigated whether manipulating dietary phosphate influences atherogenesis or insulin sensitivity in ...

Body mass index, fasting insulin, and aspartate aminotransferase or alanine aminotransferase ratio also differed.. The team found that quantitative insulin sensitivity check index, and hyaluronic acid differed between the 2 groups.. Hyaluronic acid composite index for distinguishing steatosis from nonalcoholic steatohepatitis was calculated.. The team calculated this index by summing up risk factors that included age 50 years or more, and female gender.. Other risk factors assessed were aspartate aminotransferase 45 IU/l or more, and body mass index 30 mg/kg2 or more.. The index was also calculated by an aspartate aminotransferase/alanine aminotransferase ratio of 0.8 or more, and hyaluronic acid of 55 mcg/l or more.. The team determined the accuracy of the index by receiver operating characteristic analysis, and found this to be 0.76.. The presence of 3 or more risk factors had a sensitivity of 74% and a specificity of 66%.. In addition, the researchers noted that a hyaluronic acid cutoff of 45 ...

An overweight child, or a child with a tendency to carry excess weight around the waist - may be at risk of being INSULIN RESISTANT!. In South Africa, about one in three children are overweight!. 80 % of individuals that are overweight are insulin resistant.. Children with Insulin Resistance have a very good chance of getting diabetes within 2 years of being diagnosed with insulin resistance if it is not treated successfully.. Insulin Resistance in children (as with adults) is also associated with an increased incidence (the chance of getting something) of heart disease, stroke or being overweight later in life.. When is a child at risk of developing or having Insulin Resistance?. -Any child or teenager who is overweight especially if they carry excess weight around their stomach, is at risk of developing or having insulin resistance ...

Why are Asian Americans at higher risk of developing type 2 diabetes than Caucasian Americans, and prone to develop the disease at lower body weights? One part of this puzzle may lie in the transition from traditional high-fiber, low-fat Asian diets to current westernized diets, which may pose extra risks for those of Asian heritage, says George King, M.D., Senior Vice President and Chief Scientific Officer at Joslin Diabetes Center and the senior author of the study.. A Joslin randomized clinical trial now has demonstrated that both Asian Americans and Caucasian Americans at risk of type 2 diabetes who adopted a rigorously controlled traditional Asian diet lowered their insulin resistance. (A leading risk factor for developing the disease, insulin resistance is a condition in which the body struggles to use the hormone insulin, which helps to metabolize sugar.). Moreover, when both groups of participants then switched to consuming typical western fare, the Asian Americans experienced greater ...

For one, it can make it very difficult for you to control your weight. More importantly, this is a prediabetic state that puts you at a much higher risk for developing diabetes and having a heart attack. Often people with insulin resistance struggle to maintain their weight, even though they may only eat one meal a day.. It is not always how much you eat, but what you eat.. People with insulin resistance develop higher than normal levels of insulin in their blood. Insulin is a hormone produced by the pancreas that helps to keep our blood sugar normal. People with insulin resistance do not metabolize carbohydrates (sugar, pasta, potatoes, etc) the same as those without. As they continue to eat a diet high in carbohydrates, their cells dont want to take in any more sugar or fat, so they become RESISTANT. The pancreas then has to produce more insulin to control the blood sugar. The insulin rapidly moves the blood sugar into fat, muscle and liver cells. Sugar in fats cells gets turned fat ...

All previous studies that investigated the association between abdominal fat distribution and insulin resistance evaluated subcutaneous and visceral fat area and/or volume, but these values were not related to the body type of each subject. In the present study we have examined the association between abdominal fat distribution and peripheral (muscle)/hepatic sensitivity to insulin using the visceral to abdominal subcutaneous fat area ratio (VF/SF ratio) in male patients with type 2 diabetes mellitus. This ratio defines the predominancy of visceral or subcutaneous abdominal adiposity, independent of the body type of each individual. Thirty-six type 2 diabetic male patients underwent a euglycemic insulin clamp (insulin infusion rate = 40 mU/m2·min) with 3-3H-glucose to measure insulin-mediated total body (primarily reflects muscle) glucose disposal (TGD) and suppression of endogenous (primarily reflects liver) glucose production (EGP) in response to a physiologic increase in plasma insulin concentration

During recent times we are dealing with multiple medical complications occurring in a single pregnant woman. It is well known fact that insulin resistance is present during normal pregnancy and it is relatively diabetogenic state. In women with genetic predisposition, diabetes, hypertension and hypothyroidism complicate pregnancy resulting in increased maternal and perinatal morbidity and mortality. There was evidence in the literature regarding insulin resistance and gestational diabetes. This review analysed the literature regarding the association of diabetes, hypertension and hypothyroidism and found that there is a linkage between these three disorders in pregnant state and the insulin resistance develops by multiple molecular mechanisms both centrally and in peripheral tissues. The key mechanism is insulin receptor substrate-1 (IRS-1) which gets inactivated by serine phosphorylation and leads to hyperglycaemia which in turn leads to stimulation of beta cells of pancreas and leads to ...

We also evaluated if vimentin affects insulin resistance in HFD-fed obese mice and found that Vim−/− mice had significantly lower fasting glucose level and improved glucose tolerance compared to control mice. In contrast, there was no difference in blood insulin level between the two groups (Fig. 2D). GLUT4, the predominant insulin-responsive glucose transporter isoform, plays a key role in the transport of extracellular glucose into insulin-sensitive cells in vivo [29,30,31]. There have been several studies revealing the role of GLUT4 in diabetes in mice. Overexpression of GLUT4 in fat reversed insulin resistance in muscle-GLUT4−/− mice [32]. GLUT4 overexpression improved insulin sensitivity and fasting triglyceridemia in HFD-fed transgenic mice [33]. In our study, GLUT4 was 22% lower in total cell lysates and 50.3% lower in the membrane fraction of vimentin-null adipocytes (Fig. 3E). Our finding corresponds to a previous report that vimentin mediates insulin-sensitive GLUT4 ...

Abstract: Obesity is a major risk factor for insulin resistance (IR) and its attendant complications. The pathogenic mechanisms linking them remain poorly understood, partly due to a lack of intermediary monogenic human phenotypes. Here, we report on a monogenic form of IR-prone obesity, Alström syndrome (ALMS). Twenty-three subjects with monogenic or polygenic obesity underwent hyperinsulinaemic-euglycemic clamping with concomitant adipose tissue (AT) microdialysis and an in-depth analysis of subcutaneous AT histology. We have shown a relative adipose tissue failure in monogenic obese cohort; a finding supported by observations in a novel conditional mouse model (Almsflin/flin) and ALMS1-silenced human primary adipocytes. Whereas, selective reactivation of ALMS1 gene in adipose tissue of an ALMS conditional knockdown mice model (Almsflin/flin;Adipo-Cre+/-) restores systemic insulin sensitivity and glucose tolerance. Hence, we show for the first time the relative adipose tissue failure in human ...