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 ...
This trial is entitled "Bumetanide has a more favourable effect on insulin resistance than furosemide in patients with heart failure - a pilot study".
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.
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. ...
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 = ...
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.
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 ...
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 ...
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.. ...
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 ...
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): ...
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 ...
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
Background: Polycystic ovarian syndrome (PCOS) is a common disease among women in fertility ages and cause severe insulin resistance. Hyperhomocysteinaemia is said to be among the features of PCOS that could influence its outcome. Objective: This study aimed to investigate whether hyperhomocysteinaemia exists in PCOS and if it is related to insulin resistance in the affected patients. Materials and Methods: This prospective study was carried out in a university based fertility clinic. Sixty four PCOS patients and 50 normo ovulatory controls were reviewed for fasting glucose, insulin, homocysteine, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) plasma levels in the blood sample of the 3rd day of their menstrual cycle. Insulin resistance was determined with the fasting glucose (mmol/L) to insulin (mIU/L) ratio and HOMA-IR (Homeostasis model assessment- Insulin resistance). Independent-samples T-test and linear regression test were utilized to analyze the obtained data. Results: ...
The time immediately before and after birth may be a sensitive period related to programming cardiometabolic risk. The present prospective study, performed in children born at term after a noncomplicated pregnancy, shows that birth weight and postnatal weight gain exert independent influences on cardiometabolic parameters at 5 years of age. Although birth weight influenced the metabolic parameters, insulin levels, homeostatic model assessment index, and postnatal weight gain influenced both metabolic parameters and blood pressure values. Throughout the study, systolic blood pressure was related to weight gain, and at 5 years the heaviest children had the highest systolic blood pressure. Moreover, the highest values of insulin, homeostatic model assessment index, and triglycerides were related to both weight gain and current weight. Interestingly, small for gestational age children had the highest values of fasting insulin and homeostatic model assessment index and the lowest high-density ...
In other words, skeletal muscle insulin resistance - and thus, to a large extent, overall insulin resistance - in diabetic subjects is due to reduced mitochondria production and/or activity and reduced insulin signaling in muscle cells. Exercise has been shown to reverse these deficits.. As the authors conclude:. Given the strong evidence for a direct role of physical activity in the prevention of insulin resistance, and the fact that exercise training increases mitochondrial biogenesis and improves glucose tolerance and insulin action in individuals with insulin resistance and type 2 diabetes, the question of why such a potent modulator of these conditions is not more commonly prescribed is perplexing and should be of utmost concern to medical health care professionals worldwide. To continue to attack the growing health burden by investing almost exclusively in strategies that target secondary and tertiary treatment of chronic disease states (i.e. pharmaceutical interventions) is extremely ...
Diminished tissue sensitivity to insulin is a central feature of various pathological conditions termed the metabolic syndrome (MS) [1]. Insulin resistance and hypertension are key components of MS and often co-exist. Since patients with MS are commonly afflicted with cardiovascular morbidities, MS and CVDs share common pathways, such as, activated RAS, increased oxidative stress, defective glucose and lipid metabolism, low grade inflammation and endothelial damage [1,2].. The effects of the systemic RAS on blood pressure and glucose metabolism have been well demonstrated [9], and local tissue RAS in the skeletal muscle, vasculature, adipocytes and pancreas may also play an important role in the development of insulin resistance and vascular injury in diabetic and hypertensive diseases [14,26]. Ang II (via AT1R), the predominant component of RAS, induces insulin resistance through variety of mechanisms including inhibition of insulin signaling and insulin mediated glucose uptake in the skeletal ...
This study is a single-center, randomized and single blinded, placebo-controlled, 6-week, parallel design study with follow-up to evaluate strawberry-associated chronic improvements in insulin action resulting in reduced whole body insulin resistance and improved glucose tolerance. This study will take approximately 11~12 weeks.. Subjects will follow an extremely limited polyphenolic diet throughout the duration of their participation in the study.. The limited diet will begin 7 days before the first study visit and end before the last study visit. Following the polyphenol-free 7-day run in period, at Week 0, subjects will be scheduled to return to the Center for sequence randomization, an Oral Glucose Tolerance Test (OGTT) as well as a Flow Mediated Dilation (FMD) procedure to measure endothelial function. Subjects will incorporate either one of tow Placebo Beverages (PBO1, n=15; PBO2, n=15) or Strawberry Beverage (STR, n=15, an optimal strawberry test dose of 40 g/d) into their diet daily for ...
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 a gene, mitochondria, insulin resistance, and how well the bodys metabolism functions in causing diabetes. Suppressing a similar gene in mice called Nat1, causes metabolic dysfunction, such as lower insulin sensitivity and higher levels of blood sugar, insulin and triglycerides. In addition, mice without the Nat1 gene gained more weight and showed a decreased ability to use fat for energy. This new study reveals that suppressing the expression of the Nat1 gene in mice hinders the function of mitochondria. These cell structures make ATP, the energy of cells, without which the cells cannot survive. Individuals with Insulin resistance dont necessarily develop type 2 diabetes. However, the condition will result in decreased ...
In the present study, we note multiple findings that provide an understanding of PM2.5 mediated effects on whole body IR in mice. The findings include: (1) Exposure to PM2.5 for 6 months induces whole body impairment in insulin responses but not intraperitoneal glucose tolerance; (2) CCR2 deficiency failed to improve PM2.5-impaired insulin sensitivity and exaggerated PM2.5-induced hyperglycemia in mice. (3) CCR2 deficiency inhibited macrophage infiltration in VAT. (4) However, CCR2 deficiency showed both inhibitory and exaggerated effects on inflammation in the liver, accompanied with dysregulation of gluconeogenesis by targeting the rate limiting enzyme of PEPCK.. The link between exposure to environmental factors in air and propensity to type 2 diabetes has gained only recent attention [1, 2, 12, 13]. To mimic real-world chronic exposures over a good part of rodent lifespan, we exposed 2-months old mice for a 6-months period and investigated its association with IR with the whole body ...
Non-Alcoholic Fatty Liver Disease (NAFLD) is associated with multi-organ (hepatic, skeletal muscle, adipose tissue) insulin resistance (IR). Exercise is an effective treatment for lowering liver fat but its effect on insulin resistance in NAFLD is unknown. We aimed to determine whether supervised exercise in NAFLD would reduce liver fat and improve hepatic and peripheral (skeletal muscle and adipose tissue) insulin sensitivity.Sixty nine NAFLD patients were randomised to 16 weeks exercise supervision ( n =38) orcounselling ( n =31) without dietary modification.All participants underwent magnetic resonance imaging/spectroscopy to assess changes in body fat, and in liver and skeletal muscle triglyceride, before and following exercise/counselling. To quantify changes in hepatic and peripheral insulin sensitivity, a pre-determined subset ( n =12 per group) underwent a two-stage hyperinsulinaemic euglycaemic clamp pre- and post-intervention. Results are shown as mean (95% CI). Fifty participants (30 ...
TY - JOUR. T1 - Adipokine Dysregulation and Insulin Resistance with Atherosclerotic Vascular Disease. T2 - Metabolic Syndrome or Independent Sequelae?. AU - Satish, Mohan. AU - Saxena, Shailendra K.. AU - Agrawal, Devendra K.. PY - 2019/1/1. Y1 - 2019/1/1. N2 - Adipokine dysregulation and insulin resistance are two hallmark sequelae attributed to the current clinical definition of metabolic syndrome (MetS) that are also linked to atherosclerotic vascular disease. Here, we critically discuss the underlying pathophysiological mechanisms and the interplay between the two sequelae. Adipokine dysregulation is involved with decreased nitric oxide, vascular inflammation, and insulin resistance in itself to promote atherosclerosis. Insulin resistance is involved with endothelial dysfunction by direct and indirect mechanisms that also promote vascular inflammation and atherosclerosis. These mechanisms are discussed in atherosclerosis irrespective of MetS, and to evaluate the possibility of synergism in ...
TY - JOUR. T1 - Evaluation of the long-term effects of gastric inhibitory polypeptide-ovalbumin conjugates on insulin resistance, metabolic dysfunction, energy balance and cognition in high-fat-fed mice. AU - Irwin, Nigel. AU - Montgomery, Ian A.. AU - Flatt, Peter. PY - 2012/7. Y1 - 2012/7. N2 - The effects of active immunisation with gastric inhibitory polypeptide (GIP) or (proline3)GIP ovalbumin conjugates on insulin resistance, metabolic dysfunction, energy expenditure and cognition were examined in high-fat-fed mice. Normal mice were injected (subcutaneously) once every 14 d for 98 d with GIP-ovalbumin conjugates, with transfer to a high-fat diet on day 21. Active immunisation resulted in GIP antibody generation and significantly (P,0.01 to P,0.001) reduced circulating non-fasting plasma insulin concentrations compared to high-fat control mice from day 70 onwards. The glycaemic responses to intraperitoneal glucose or nutrient ingestion were significantly improved in all treated mice, with ...
Insulin resistance is the main factor involved in the occurrence of the metabolic syndrome and later development of type2 diabetes. Despite decades of research on hormones target tissues and the identification of most diverse candidates, the factors responsible for insulin resistance are still largely undefined. There is also a large discrepancy between in vitro and in vivo insulin sensitivity. Finally it is increasingly demonstrated that insulin resistance is found very early in life, long before metabolic syndrome is established. In search for commonalities, this book deals therefore with a new hypothesis considering microcirculation as one prime, possibly causal effector of insulin resistance. To present this novel hypothesis, the specificities of microvascular physiological mechanisms and the limits of interpretations of data according to the measurement techniques used are first thoroughly described. Several chapters deal with experimental and clinical investigations showing the ...
Insulin resistance is the main factor involved in the occurrence of the metabolic syndrome and later development of type2 diabetes. Despite decades of research on hormones target tissues and the identification of most diverse candidates, the factors responsible for insulin resistance are still largely undefined. There is also a large discrepancy between in vitro and in vivo insulin sensitivity. Finally it is increasingly demonstrated that insulin resistance is found very early in life, long before metabolic syndrome is established. In search for commonalities, this book deals therefore with a new hypothesis considering microcirculation as one prime, possibly causal effector of insulin resistance. To present this novel hypothesis, the specificities of microvascular physiological mechanisms and the limits of interpretations of data according to the measurement techniques used are first thoroughly described. Several chapters deal with experimental and clinical investigations showing the ...
Insulin resistance refers to the inability of the body tissues to respond properly to insulin. Insulin lets sugar (glucose) enter body cells, where it is used for energy. Insulin also helps muscles, fat, and liver cells store sugar to be released when it is needed. If the body tissues do not respond properly to insulin, the blood sugar level rises.. Insulin resistance causes the pancreas to release too much insulin (hyperinsulinemia). It may also cause the liver to release too much sugar into the blood.. Several things may increase insulin resistance, including:. ...
Insulin resistance is often associated with obesity and can precipitate type 2 diabetes. To date, most known approaches that improve insulin resistance must be preceded by the amelioration of obesity and hepatosteatosis. Here, we show that this provision is not mandatory; insulin resistance and hype …
In the current study, we fed WHHL rabbits with two kinds of diets: HFFD (rich in sugar and fat with reduced protein and fibers) and standard chow diet (protein- and fiber-rich). Although both groups consumed an equal amount of calorie of each diet, HFFD feeding led to prominent IR accompanied by elevated plasma lipids, hepatic steatosis and adipose accumulation, even though the body weight was unchanged. Increased plasma levels of lipids are basically caused by high uptake of free fatty acids into the liver where they can be synthesized into VLDLs, which are accumulated in the plasma. At the same time, VLDL accumulation was further enhanced due to delayed catabolism of VLDLs in the context of deficiency of LDL receptors in WHHL rabbits. It should be pointed out that high-fat diet feeding did not increase plasma lipids in wild-type rabbits which have normal LDL receptors [20]. This notion is further supported by our Triton experiments along with RT-PCR analysis showing that there was increased ...
Objective: In this retrospective analysis of the European Group for the Study of Insulin Resistance database, a clamp data pooling project, a cardiovascular risk score (CVS) was assessed to verify whether hyperinsulinemia and/or insulin resistance were independent cardiovascular risk factors and to investigate how menopause affected CVS and insulin resistance. Design: Information was obtained on whole-body glucose uptake (M), determined by the euglycemic hyperinsulinemic clamp technique, normalized by fat-free mass (FFM), and insulin concentration (1) at a steady state. Body composition was estimated using a labeled water technique or bioimpedance. Other parameters measured included blood pressure, lipid levels, and waist-to-hip ratio. CVS was computed using a structural equation model that included age, body mass index, blood lipids, and blood pressure. The study population included 523 normal and overweight patients. Women were grouped according to fertility status, and men, according to age ...
Glucose metabolism alterations were detected in 81.4% of the participants: 63.8% with NGT-HI, 15.3% with IGT, and 2.3% with T2DM. The median levels of homeostasis model assessment-insulin resistance (HOMA-IR) in patients with IGT (8.63) were significantly greater than those in the patients with NGT (4.04) (p,0.01). During the follow-up, 22 patients (14.4%) developed T2DM significantly more from the IGT group (nine of 33 cases, 27.3%) than the NGT-HI group (12 of 108 cases, 11.1%) (p=0.022). The predicting parameters for T2DM conversion were weight status, body mass index (BMI), FBG, fasting insulin, alanine transaminase (ALT) levels, and HOMA-IR. ...
You have been taught that carbohydrates are your enemy and as a result of that all diabetics here carbohydrates. Low carb, high fat diets are often prescribed for diabetic people as a healthy alternative. Scientific studies done in different periods of time found that it was not high carbohydrates, but high fat diets that resulted in insulin resistance and type 2 diabetes. Studies also found that a diet composed of rice and fruit, simple low-fat, high sugar and carbohydrates foods had no negative effect on insulin resistance at all and actually improved it. Generally, it is believed that the foods high in carbohydrates will worsen the diabetes problem and will also increase the requirement for insulin and medicines. Different diets have been developed based on these principles. Studies found that increase carbohydrate in fact improved insulin resistance in people. The main factor of diabetes is insulin resistance and if that can be addressed, it will help us reverse diabetes and make the patient ...
Washington D.C. [USA], Mar. 23 : Higher level of blood sugar and insulin resistance, accompanied by obesity and physical inactivity, is also linked to more rapid decline in cognitive performance, says a new study.. The study, by Tel Aviv University, finds that both diabetic and non-diabetic subjects with insulin resistance experienced accelerated cognitive decline in executive function and memory.. The research, published in the Journal of Alzheimers Disease, was jointly led by Prof. David Tanne and Prof. Uri Goldbourt and conducted by Dr. Miri Lutski, all of TAUs Sackler School of Medicine.. "These are exciting findings because they may help to identify a group of individuals at increased risk of cognitive decline and dementia in older age," says Prof. Tanne.. Adding, "We know that insulin resistance can be prevented and treated by lifestyle changes and certain insulin-sensitizing drugs. Exercising, maintaining a balanced and healthy diet, and watching your weight will help you prevent ...
Harvard Medical School researchers at Joslin Diabetes Center have created the first induced pluripotent stem cells (iPSCs) that offer a human model of insulin resistance, a key driver of type 2 diabetes.. "This is one of the very first studies of human iPSC models for type 2 diabetes, and it points out the power of this technology to look at the nature of diabetes, which is complex and may be different in different individuals," said C. Ronald Kahn, the HMS Mary K. Iacocca Professor of Medicine and chief academic officer at Joslin.. Until now, scientists examining the causes and effects of insulin resistance have struggled with a general lack of human cell lines from tissues such as muscle, fat and liver that respond significantly to insulin, said Kahn. Studying insulin resistance as it progresses through pre-clinical stages of type 2 diabetes has been particularly challenging.. "There have been no good human cell models to study insulin resistance, but such cells can now be made with iPSCs," ...
WC: waist circumference; BMI: body mass index; HOMA-IR: homeostasis model assessment-insulin resistance.. Using the stepwise multiple regression analysis without considering age as a covariate, the eGFR-MDRD was correlated in males with SBP (r -0.336; p = 0.019), with waist circumference (r -0.499; p = 0.000), with BMI (r - 0.376; p = 0.007), with serum total cholesterol (r -0.384; p = 0.000), with serum uric acid (r -0.415; p = 0.000), and with CRP (r -0.162; p = 0.016). In females, eGFR-MDRD was correlated with SBP (r -0.371; p = 0.000), with waist circumference (r -0.191; p = 0.018), with fasting serum glucose (r -0.201; p = 0.003), with serum total cholesterol (r -0.374; p = 0.000), with LDL cholesterol (r -0.332; p = 0.024), with serum triglycerides (r -0.085; p = 0.000), and with serum uric acid (r -0.401; p = 0.000). When we included age as covariant only the serum total cholesterol (p = 0.005) and the serum uric acid (p = 0.000) in males, and the serum total cholesterol (p = 0.004), ...
No. Adipocytes control whole body insulin sensitivity. They see no insulin if they have had their insulin receptors knocked out. They sport minimal (zero?) GLUT4s on their surface. What fat they contain has been accumulated without the assistance of insulin. I think it is reasonable to assume they have some GLUT1s on their surface. Any glucose taken up will be available for lipid synthesis but, without insulins action, there will be no insulin induced SCD1 desaturase activity. So palmitate it is and, in the absence of insulins action, this will be freely released and should signal whole body insulin resistance. But it doesnt. It does exactly the same as the palmitic acid does in SCD1 knockout mice. Peroxisiomes. FIRKO mice eat more, weigh less and (probably) generate more heat than WT mice do. They are insulin sensitive everywhere except for their adipocytes. They behave exactly as SCD1-/- mice do but get there by a rather indirect route. Excess palmitate is burned in peroxisomes and the C8 ...
Although the role of insulin resistance in the pathophysiology of type 2 diabetes mellitus is well accepted, the relationship between insulin resistance and blood pressure remains controversial. Nearly 40 years ago, Welborn and colleagues5 observed that nondiabetic patients with essential hypertension had significantly higher plasma insulin concentrations than did normotensive individuals. This positive relationship has been confirmed in several longitudinal studies, but the results are not entirely consistent. In some studies, the association between hyperinsulinemia and incident hypertension disappeared after adjustment for body mass index (BMI), suggesting that the association is confounded or mediated through obesity. Therefore, the causal role of insulin resistance/compensatory hyperinsulinemia in the development of hypertension continues to be debated.. As reported in this issue of Circulation, Ärnlöv and colleagues6 investigated the relationship between insulin sensitivity, using ISI, ...
RESULTS: Even after adjusting for confounding factors, plasma TG levels were significantly different at baseline among three genotype subgroups: TT, 126 ± 68 mg/dl; TC, 134 ± 74 mg/dl; and CC, 172 ± 101 mg/dl. Lifestyle modification resulted in significant reductions in plasma TG levels in the TT, TC, and CC genotype subgroups: -21.9 ± 61.0 mg/dl, -20.9 ± 51.0 mg/dl, and -42.6 ± 78.5 mg/dl, respectively, with no significant differences between them. In a stepwise regression analysis, age, APOA5 T-1131C, body mass index (BMI), homeostasis model assessment-insulin resistance (HOMA-IR), and the 18:1/18:0 ratio showed independent association with plasma TG levels at baseline. In a general linear model analysis, APOA5 T-1131C C-allele carriers showed significantly greater TG reduction with decreased energy balance than wild type carriers after adjustment for age, gender, and baseline plasma TG levels ...