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InsulinInsulin ResistanceReceptor, InsulinGlucose Clamp TechniqueGlucose Tolerance TestBlood GlucoseGlucoseObesitySensitivity and SpecificityDiabetes Mellitus, Type 2Hypoglycemic AgentsAdipose TissueHyperinsulinismMuscle, SkeletalInsulin Receptor Substrate ProteinsGlucose IntoleranceFastingAdiponectinBody WeightInsulin-Secreting CellsFatty Acids, NonesterifiedLiverIslets of LangerhansC-PeptideTriglyceridesThiazolidinedionesLeptinBody CompositionAdipocytesGlucose Transporter Type 4HyperglycemiaLipid MetabolismLipidsHomeostasisDiet, High-FatInsulin, Long-ActingAdiposityBody Mass IndexThinnessInsulin AntagonistsDietary FatsMice, ObeseEatingInsulin AntibodiesPrediabetic StateGlucagonMetforminSignal TransductionEnergy MetabolismDiabetes MellitusReference ValuesDiabetes Mellitus, ExperimentalTime FactorsInsulin Infusion SystemsMetabolic Syndrome XGlycogenInsulin LisproLipolysisMice, Inbred C57BLPhosphorylation3T3-L1 CellsFatty LiverPPAR gammaProinsulinPostprandial PeriodMice, KnockoutPolycystic Ovary SyndromeFatty AcidsIntra-Abdominal FatDeoxyglucoseRats, ZuckerRats, WistarAdipokinesHemoglobin A, GlycosylatedDietary CarbohydratesDietRNA, MessengerBlood PressureInsulin, Regular, HumanMonosaccharide Transport ProteinsWeight LossDose-Response Relationship, DrugThiazolesGluconeogenesisProto-Oncogene Proteins c-aktInsulin AspartDiabetes Mellitus, Type 1Adipose Tissue, WhiteGlucagon-Like Peptide 1Insulin, IsophaneResistinInsulin, Regular, PorkGene Expression RegulationDisease Models, AnimalRats, Sprague-DawleyCross-Over StudiesKineticsInsulin-Like Growth Factor ICells, CulturedMuscle Proteins

SecretionImprove insulin sensitivityObesityEffects of circulaHyperglycemiaReceptorsObeseResistance and impairedHomeostasisRosiglitazonePioglitazoneAdipose tissueLipolysisDiabetic ratsDyslipidemiaPancreaticEndogenous insulinPostprandial insulinAssociated with insulin resistanceSkeletalBlood glucoseInflammationAdipocytesMetabolicGlycogen synthesisHyperinsulinemiaConcentrationsDefectsReductionsReductionGlycemicCompensatoryHypertriglyceridemiaDiabetesSynthesisCholesterol0.01GeneTypeThiazolidinedione

Secretion5

• GLP-1 is an intestinally-derived peptide that stimulates insulin secretion in response to food intake, as well as reducing the rate of gastric emptying, thus promoting satiety and weight loss. (ddw-online.com)
• It is known that resveratrol affects insulin secretion and blood insulin concentration. (anti-agingfirewalls.com)
• Peripheral CB 1 R blockade, in vivo depletion of macrophages or macrophage-specific knockdown of CB 1 R reverses or prevents these changes and restores normoglycemia and glucose-induced insulin secretion. (nature.com)
• It is characterized by hyperglycemia and defective production and/or secretion of insulin and complications in the heart, kidney, and neural system leading to death, which have drawn notable attention to the management of diabetes. (frontiersin.org)
• It may also modulate insulin secretion and skeletal muscle fatty acid oxidation with glucose uptake. (biotechpeptides.com)

Improve insulin sensitivity2

• A wealth of published data documents the ability of carnitine to improve insulin sensitivity, mitochondrial function, and cardiovascular health. (lifeextension.com)
• AICAR may improve insulin sensitivity and lipid metabolism via its possible anti-inflammatory role in different metabolic pathways. (biotechpeptides.com)

Obesity11

• Dietary restriction of leucine and the other BCAAs can reverse diet-induced obesity in wild-type mice by increasing energy expenditure, and can restrict fat mass gain of hyperphagic rats. (wikipedia.org)
• Insulin resistance is a major metabolic feature of obesity and is a key factor in the etiology of a number of diseases, including type 2 diabetes. (jci.org)
• In this review, we discuss potential mechanisms by which brief nutrient excess and obesity lead to insulin resistance and propose that these mechanisms of action are different but interrelated. (jci.org)
• We then discuss how obesity leads to insulin resistance via a complex interplay among systemic fatty acid excess, microhypoxia in adipose tissue, ER stress, and inflammation. (jci.org)
• In particular, we focus on the hypothesis that the macrophage is an important cell type in the propagation of inflammation and induction of insulin resistance in obesity. (jci.org)
• Overall, we provide our integrative perspective regarding how nutrients and obesity interact to regulate insulin sensitivity. (jci.org)
• The Nlrp3 inflammasome has been implicated in obesity-induced insulin resistance and beta cell failure. (nature.com)
• Bradykinin elicited substantial dilation in coronary arterioles, with a similar magnitude in obese and non-obese patients (to 10 -8 M: 55 ± 5% vs. 46 ± 5%, P = 0.20), but with significantly enhanced sensitivity in obesity (EC50: 8.2x10 -9 M vs. 1.9x10 -8 M, respectively, P = 0.03). (biomedcentral.com)
• TGF-β, especially TGF-β1 as an uppermost isoform of TGF-β superfamily, may play a very essential role in the development of insulin resistance and obesity and finally, diabetes. (frontiersin.org)
• Encouraging preclinical results suggest that β3-AR agonists could also improve obesity-related metabolic disease by increasing brown adipose tissue (BAT) thermogenesis, white adipose tissue (WAT) lipolysis, and insulin sensitivity.METHODS We treated 14 healthy women of diverse ethnicities (27.5 ± 1.1 years of age, BMI of 25.4 ± 1.2 kg/m2) with 100 mg mirabegron (Myrbetriq extended-release tablet, Astellas Pharma) for 4 weeks in an open-label study. (jci.org)
• Replacement of GH in adults with GHD markedly reduces central obesity and substantially reduces total cholesterol levels but has produced little change in other risk factors, particularly insulin resistance and dyslipidemia. (medscape.com)

Effects of circula1

• Insulin resistance is defined as an inadequate response by insulin target tissues, such as skeletal muscle, liver, and adipose tissue, to the physiologic effects of circulating insulin. (jci.org)

Hyperglycemia7

• In animal models of diabetes, pioglitazone reduces the hyperglycemia, hyperinsulinemia, and hypertriglyceridemia characteristic of insulin-resistant states such as type 2 diabetes. (globalrph.com)
• The antidiabetic activity of rosiglitazone has been demonstrated in animal models of type 2 diabetes in which hyperglycemia and/or impaired glucose tolerance is a consequence of insulin resistance in target tissues. (globalrph.com)
• This altered glucose metabolism state is associated with an increased risk of developing T2DM (Figure 1), although other parameters including excess adiposity, inflammation and dyslipidemia are risk factors associated with the development of insulin resistance, loss of pancreatic function, worsening of hyperglycemia and progression to diabetes (1). (ddw-online.com)
• Moreover, numerous data indicate that in diabetic rats, resveratrol is able to reduce hyperglycemia. (anti-agingfirewalls.com)
• Type 2 diabetes mellitus (T2DM) progresses from compensated insulin resistance to beta cell failure resulting in uncompensated hyperglycemia, a process replicated in the Zucker diabetic fatty (ZDF) rat. (nature.com)
• Type 2 diabetes is a complex metabolic disorder characterized by hyperglycemia, impaired glucose tolerance and insulin resistance associated with dyslipidemia and hypertension. (biomedcentral.com)
• Dysregulated autophagy in pancreatic β cells due to hyperglycemia, oxidative stress, and inflammation is associated with diabetes and accompanied by dysregulated autophagy in insulin target tissues and the progression of diabetic complications. (frontiersin.org)

Receptors6

• PPAR receptors are found in tissues important for insulin action such as adipose tissue, skeletal muscle, and liver. (globalrph.com)
• Activation of PPARγ nuclear receptors modulates the transcription of a number of insulin responsive genes involved in the control of glucose and lipid metabolism. (globalrph.com)
• Activation of PPARγ nuclear receptors regulates the transcription of insulin-responsive genes involved in the control of glucose production, transport, and utilization. (globalrph.com)
• Endocannabinoids contribute to insulin resistance through activation of peripheral CB 1 receptors (CB 1 Rs) and also promote beta cell failure. (nature.com)
• Thus, in rats with normal leptin receptors but not in Zucker Diabetic Fatty rats, nonadipocytes and adipocytes esterify FFA, store them as TG, and later oxidize them intracellularly via an 'indirect pathway' of intracellular fatty acid metabolism controlled by leptin. (duke.edu)
• In addition, GIP and GLP-1 act on insulin receptors to facilitate insulin-receptor binding, resulting in optimal glucose metabolism. (openmedicinalchemistryjournal.com)

Obese6

• Alpha-Linolenic Acid Supplementation Prevents Exercise-Induced Improvements in White Adipose Tissue Mitochondrial Bioenergetics and Whole-Body Glucose Homeostasis in Obese Zucker Rats. (uoguelph.ca)
• Alpha-Linolenic Acid Supplementation and Exercise Training Reveal Independent and Additive Responses on Hepatic Steatosis in Obese Rats. (uoguelph.ca)
• Rosiglitazone reduces blood glucose concentrations and reduces hyperinsulinemia in the ob/ob obese mouse, db/db diabetic mouse, and fa/fa fatty Zucker rat. (globalrph.com)
• In islets of obese Zucker Diabetic Fatty rats with leptin receptor mutations, leptin had no effect in vivo or in vitro. (duke.edu)
• Contractile activity restores insulin responsiveness in skeletal muscle of obese Zucker rats. (ecu.edu)
• Insulin-stimulated glucose transport is decreased in obese humans and rats. (ecu.edu)

Resistance and impaired2

• Expression of NLRP3 inflammasome and T cell population markers in adipose tissue are associated with insulin resistance and impaired glucose metabolism in humans. (nature.com)
• Type 2 DM is a heterogeneous, progressive disorder initially characterized by impaired glucose tolerance and compensatory hyperinsulinemia, which in the later stages, develops severe insulin resistance and impaired beta cell function [ 2 , 3 ]. (biomedcentral.com)

Homeostasis3

• Our data show that treatment with FIN improves kidney and vascular damage in a new rat model of DKD with T1D associated with a reduction in inflammation, fibrosis and osteogenic factors independently from changes in glucose homeostasis. (met-vasc.com)
• However, larger, adequately powered, randomized, placebo-controlled, double-blind trials examining multiple measures of carbohydrate and lipid metabolism and insulin homeostasis are needed. (lww.com)
• The suppression of inflammation results in increased insulin sensitivity with improved glucose homeostasis. (biotechpeptides.com)

Rosiglitazone4

• We examined the effect of three months of rosiglitazone treatment (4 mg b.i.d.) on whole-body insulin sensitivity and in vivo peripheral adipocyte insulin sensitivity as assessed by glycerol release in microdialysis from subcutaneous fat during a two-step (20 and 120 mU · m −2 · min −1 ) hyperinsulinemic-euglycemic clamp in nine type 2 diabetic subjects. (diabetesjournals.org)
• Rosiglitazone, a member of the thiazolidinedione class of antidiabetic agents, improves glycemic control by improving insulin sensitivity. (globalrph.com)
• In animal models, the antidiabetic activity of rosiglitazone was shown to be mediated by increased sensitivity to insulin's action in the liver, muscle, and adipose tissues. (globalrph.com)
• PPAR-gamma agonists, also known as thiazolidinediones (TZDs), such as Pioglitazone and Rosiglitazone increase insulin sensitivity, reduce levels of blood glucose, insulin and triglycerides with a concomitant reduction in BP and improvement in endothelial function [ 8 , 9 ]. (biomedcentral.com)

Pioglitazone7

• Unlike sulfonylureas, pioglitazone is not an insulin secretagogue. (globalrph.com)
• The metabolic changes produced by pioglitazone result in increased responsiveness of insulin-dependent tissues and are observed in numerous animal models of insulin resistance. (globalrph.com)
• Current widespread treatments for T2DM include metformin (suppressor of hepatic glucose production), sulfonylureas (insulin secretagogues), and the thiazolidinedione pioglitazone (PPAR agonist). (ddw-online.com)
• CONCLUSIONS -These results suggest that pioglitazone therapy in type 2 diabetic patients decreases fasting and postprandial plasma glucose levels by improving hepatic and peripheral (muscle) tissue sensitivity to insulin. (diabetesjournals.org)
• The present study examined the combined effects of an antihypertensive (S-Amlodipine) and an insulin-sensitizing agent, peroxisome proliferator-activated receptor (PPAR) agonists (Pioglitazone and Ragaglitazar), on cardiovascular risk factors in aged diabetic and insulin-resistant Zucker fa/fa rats. (biomedcentral.com)
• In combination, S-Amlodipine and Pioglitazone significantly reduced blood glucose (115.1 ± 6.6 vs. 81.7 ± 4.2), BP (184.4 ± 5.0 vs. 155.1 ± 5.0), serum triglycerides (362.5 ± 47.5 vs. 211.1 ± 23.7) and glucose intolerance when compared with vehicle treated Zucker fa/fa rats. (biomedcentral.com)
• Furthermore, there was less body weight gain and food intake with S-Amlodipine and Pioglitazone combination in Zucker fa/fa rats. (biomedcentral.com)

Adipose tissue1

• The hallmarks of impaired insulin sensitivity in these three tissues are decreased insulin-stimulated glucose uptake into skeletal muscle, impaired insulin-mediated inhibition of hepatic glucose production in liver, and a reduced ability of insulin to inhibit lipolysis in adipose tissue. (jci.org)

Lipolysis1

• 0.05) and a 52% increase in the sensitivity of peripheral adipocytes to the inhibitory effects of insulin on lipolysis ( P = 0.04). (diabetesjournals.org)

Diabetic rats2

• Figure 3: Macrophage content and Nlrp3 expression in islets of lean and diabetic rats. (nature.com)
• Taurine has also been shown in diabetic rats to decrease weight and decrease blood sugar. (wikidoc.org)

Dyslipidemia1

• [ 13 ] For these patients, concerns are the persistent insulin resistance and dyslipidemia, together with the elevated plasma insulin and lipoprotein(a) levels observed with GH replacement. (medscape.com)

Pancreatic2

• Type 2 diabetes mellitus (T2DM) is a progressive metabolic disease characterized by pancreatic β-cell dysfunction and peripheral insulin resistance, leading to defects in glucose metabolism and chronic low-grade inflammation. (frontiersin.org)
• Here we show that beta cell failure in adult ZDF rats is not associated with CB 1 R signaling in beta cells, but rather in M1 macrophages infiltrating into pancreatic islets, and that this leads to activation of the Nlrp3-ASC inflammasome in the macrophages. (nature.com)

Endogenous insulin1

• Due to its mechanism of action, AVANDIA is active only in the presence of endogenous insulin. (healthyplace.com)

Postprandial insulin3

• High-fat diet results in postprandial insulin resistance that involves parasympathetic dysfunctionParasympatheticnitric-oxidevisceraladipositypostmealadipose-tissueobesenervesskeletal-musclewhiteblockadeoxidativeHigh-fatdietzuckerObesitystressglucoserattestInsulinristresistancenervous-systemsynthasesensitivityObesityHigh-fat dietInsulin resistanceParasympathetic nervesSDG 3 - Good Health and Well-beingWe are indebted to Dr Zhi Ming for sharing technical expertise and Gerald Nolette from the Central Animal Care Services of the University of Manitoba for animal care assistance. (ibict.br)
• In conclusion, fat accumulation induced by HFD is associated with postprandial insulin resistance, but not with fasting insulin resistance. (ibict.br)
• HFD-associated postprandial insulin resistance is largely mediated by impairment of parasympathetic-dependent insulin action, which correlates with adiposity. (ibict.br)

Associated with insulin resistance1

• High blood levels of leucine are associated with insulin resistance in humans, mice, and rodents. (wikipedia.org)

Skeletal5

• We discuss how pathways that "sense" nutrients within skeletal muscle are readily able to regulate insulin action. (jci.org)
• Age-Associated Impairments in Mitochondrial ADP Sensitivity Contribute to Redox Stress in Senescent Human Skeletal Muscle. (uoguelph.ca)
• Controlling CPT-I M-CoA Sensitivity in Skeletal Muscle: The Importance of AMPK-Independent Regulation of Intermediate Filaments During Exercise. (uoguelph.ca)
• In vivo hyperleptinemia, induced in normal rats by adenovirus gene transfer, depleted TG content in liver, skeletal muscle, and pancreas without increasing plasma FFA or ketones, suggesting intracellular oxidation. (duke.edu)
• Both insulin and contraction stimulate glucose transport in skeletal muscle. (ecu.edu)

Blood glucose1

• This process results in raised insulin and blood glucose levels. (biotechpeptides.com)

Inflammation2

• In the past, numerous studies investigating WAT inflammation have shown that the release of pro-inflammatory cytokines, such as TNFα, IL-6 or gp130 cytokines, are implicated in insulin-resistance [ 9 , 10 ]. (springer.com)
• Insulin resistance is considered to result from reduced sensitivity of muscles to insulin and increased uptake in the fatty tissues, which also leads to increased levels of inflammation. (biotechpeptides.com)

Adipocytes2

• In conclusion, these results support the hypothesis that thiazolidinediones enhance insulin sensitivity in patients with type 2 diabetes by promoting increased insulin sensitivity in peripheral adipocytes, which results in lower plasma fatty acid concentrations and a redistribution of intracellular lipid from insulin responsive organs into peripheral adipocytes. (diabetesjournals.org)
• The novel endocrine disruptor tolylfluanid impairs insulin signaling in primary rodent and human adipocytes through a reduction in insulin receptor substrate-1 levels. (bu.edu)

Metabolic2

• Secondary endpoints included resting energy expenditure (REE), plasma metabolites, and glucose and insulin metabolism as assessed by a frequently sampled intravenous glucose tolerance test.RESULTS Chronic mirabegron therapy increased BAT metabolic activity. (jci.org)
• Filipović D, Inderhees J, Korda A, Tadić P, Schwaninger M, Inta D, Borgwardt S. Metabolic Fingerprints of Effective Fluoxetine Treatment in the Prefrontal Cortex of Chronically Socially Isolated Rats: Marker Candidates and Predictive Metabolites . (uni-luebeck.de)

Glycogen synthesis1

• Arden C, Green AR, Hampson LJ, Aiston S, Härndahl L, Greenberg CC, Brady MJ, Freeman S, Poucher SM, Agius L. Increased sensitivity of glycogen synthesis to phosphorylase-a and impaired expression of the glycogen-targeting protein R6 in hepatocytes from insulin-resistant Zucker fa/fa rats. (bu.edu)

Hyperinsulinemia1

• In animals with hyperinsulinemia, resveratrol was found to reduce blood insulin. (anti-agingfirewalls.com)

Concentrations1

• 0.01) decreased significantly without change in fasting or glucose-stimulated insulin/C-peptide concentrations. (diabetesjournals.org)

Defects1

• [12] Recent studies have also shown that taurine can influence (and possibly reverse) defects in nerve blood flow, motor nerve conduction velocity, and nerve sensory thresholds in experimental diabetic neuropathic rats. (wikidoc.org)

Reductions1

• Exercise-Induced Reductions in Mitochondrial ADP Sensitivity Contribute to the Induction of Gene Expression and Mitochondrial Biogenesis Through Enhanced Mitochondrial H 2 O 2 Emission. (uoguelph.ca)

Reduction3

• S-Amlodipine itself caused significant reduction in glucose (115.1 ± 6.6 vs. 89.7 ± 2.7) and BP (184.4 ± 5.0 vs. 156.1 ± 4.0) with improvement in insulin sensitivity observed through oral glucose tolerance test. (biomedcentral.com)
• 4 out of the twenty tumors in handle rats demonstrated a reduction in size, whereas the remaining sixteen tumors elevated in dimension and additional eight tumors appeared throughout the study period. (tcr-signal.com)
• DM is due to a reduction in the level or effectiveness of insulin. (openmedicinalchemistryjournal.com)

Glycemic2

• Figure 1: Effects of peripheral CB 1 R blockade on body weight, adiposity, hepatic lipogenesis and glycemic control in ZDF rats. (nature.com)
• Figure 4: Effects of macrophage depletion on glycemic control and proinflammatory signaling in islets of ZDF rats. (nature.com)

Compensatory1

• In the presence of a robust compensatory insulin secretory response to insulin resistance, glucose levels can remain relatively normal. (jci.org)

Hypertriglyceridemia1

• The in vivo activity of BMS-201038, a potent inhibitor of MTP, was evaluated in a model of hypertriglyceridemia induced by Triton WR1339 and corn oil in Zucker fatty rats. (medkoo.com)

Diabetes4

• Insulin resistance is a common feature characterizing the pathogenesis of type 2 diabetes. (globalrph.com)
• By maintaining insulin sensitivity and preventing islet lipotoxicity, this activity of leptin may prevent adipogenic diabetes. (duke.edu)
• Another pathway, TGF-β signaling pathway, appears to play a part in the progression of diabetes, insulin resistance, and autoimmunity in both type 1 and 2 diabetes and complications in diabetes. (frontiersin.org)
• Taking CLA by mouth does not improve pre-meal or post-meal blood sugar or insulin levels in people with type 2 diabetes . (webmd.com)

Synthesis1

• As a dietary supplement, leucine has been found to slow the degradation of muscle tissue by increasing the synthesis of muscle proteins in aged rats. (wikipedia.org)

Cholesterol1

• In a study of 60 women with polycystic ovary syndrome, taking a flaxseed omega-3 supplement twice daily for 12 weeks improved insulin metabolism and cholesterol levels with little effect on hormone levels and lipid levels. (earthtokathy.com)

0.011

• 0.01), reduced hemoglobin A1c levels (P = 0.01), and improved insulin sensitivity (P = 0.03) and β cell function (P = 0.01). (jci.org)

Gene1

• Figure 6: Proinflammatory gene and protein expression in human macrophages and rat and human isolated islets treated with AEA, IL-1β or high glucose. (nature.com)

Type1

• We explored the effect of FIN in a novel model of type 1 diabetic Munich Wistar Frömter (MWF) rat (D) induced by injection of streptozotocin (15 mg/kg) and additional exposure to a high-fat/high-sucrose diet. (met-vasc.com)

Thiazolidinedione1

• ACTOS is a thiazolidinedione antidiabetic agent that depends on the presence of insulin for its mechanism of action. (globalrph.com)