Type 2 diabetes is widespread and its prevalence is increasing rapidly. In the US alone, approximately 41 million individuals have prediabetes, placing them at high risk for the development of diabetes. The pathogenesis of type 2 diabetes involves inadequate insulin secretion and resistance to the action of insulin. Suggestive data ...

BACKGROUND: Insulin resistance, which can lead to a number of diseases including type 2 diabetes and coronary heart disease, is believed to have evolved as an adaptation to periodic starvation. The "thrifty gene" and "thrifty phenotype" hypotheses constitute the dominant paradigm for over four decades. With an increasing understanding of ...

Both insulin resistance and dyslipidaemia are determined by genetic and environmental factors. Depending on their expression and their function, gene variants may influence either insulin action or dyslipidaemia. The purpose of this review was to give some examples from recent studies of gene variants that influence insulin signalling and the ...

Obesity is associated with an increased risk of developing insulin resistance and type 2 diabetes. In obese individuals, adipose tissue releases increased amounts of non-esterified fatty acids, glycerol, hormones, pro-inflammatory cytokines and other factors that are involved in the development of insulin resistance. When insulin resistance is accompanied by dysfunction ...

OBJECTIVES: The objectives of this study were to determine whether lower socioeconomic status (SES) is associated with changes in insulin resistance in adolescents over a 3-year period and explore moderators of this effect. METHODS: A total of 1167 healthy non-Hispanic black and white participants in the Princeton School District Study, ...

In the past decades, several cases of the syndrome of generalized glucocorticoid (GC) resistance have been reported. This familial disease is characterized by reduced cortisol effects, due to a GC receptor (GR) defect, which is compensated by hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis. As a consequence, patients present with signs ...

Insulin resistance is pathogenic for type 2 diabetes and cardiovascular disease. Several inhibitors of insulin signaling have a role in human insulin resistance. The transmembrane glycoprotein ectonucleotide pyrophosphatase phosphodiesterase 1 (E-NPP1; also known as plasma cell membrane glycoprotein PC-1) interacts with the insulin receptor and inhibits subsequent signaling by decreasing ...

The link between inflammation and diabetes is well established, but the nature of the link is unresolved. Obesity, inflammation, and insulin resistance are major characteristics of diabetes. A study by Flier and colleagues () identifies Toll-like receptor 4 signaling activated by fatty acids as part of that link. This receptor ...

Insulin resistance is a feature of a number of clinical disorders, including type 2 diabetes/glucose intolerance, obesity, dyslipidaemia and hypertension clustering in the so-called metabolic syndrome. Insulin resistance in skeletal muscle manifests itself primarily as a reduction in insulin-stimulated glycogen synthesis due to reduced glucose transport. Ectopic lipid accumulation plays ...

Insulin resistance is the major feature of the metabolic syndrome and depends on insulin secretion and insulin sensitivity. In chronic hepatitis C, insulin resistance and type 2 diabetes mellitus are more often seen than in healthy controls or chronic hepatitis B patients. Hepatitis C virus (HCV) infection promotes insulin resistance, ...

3T3-L1 adipocytes develop insulin-resistant glucose transport upon preincubation with high (25 mM) glucose, provided that insulin (0.6 nM) is included, Akt activation is impaired, and high glucose and insulin act synergistically. Considerable evidence suggests that increased glucose flux via the hexosamine biosynthesis pathway enhances the O-GlcNAc modification (O-GlcNAcylation) of some ...

CONTEXT: The aim of this article was to review the existing data on the interactions among insulin, insulin resistance, and endothelin and how those contribute to the development of hypertension in insulin-resistant states. EVIDENCE ACQUISITION: A literature search of MEDLINE database was performed to identify English-language articles published during the ...

Using non-cholesterol sterols investigation several authors postulated a hypothesis that in the metabolic syndrome cholesterol endogenous synthesis is increased and its absorption decreased. Our study is the first attempt to evaluate the direct relation of cholesterol metabolism to the principal pathogenetic phenomenon of the metabolic syndrome--namely to insulin resistance. We ...

Inflammatory states are characterized by decreased food intake, hyperglycemia, and insulin resistance. The contribution of cytokines in this phenotype is important and is exerted through activation of SOCS proteins and inhibition of insulin signaling, as well as through direct stimulation of the ob gene. Obesity, a condition that has reached ...

Hepatic insulin sensitizing substance (HISS) has been shown to account for 55% of the action of insulin in the fed state. HISS blockade leads to HISS-dependent insulin resistance (HDIR). The objective of this study was to test the hypothesis that insulin resistance produced by hemorrhage was HDIR. Insulin sensitivity was ...

The rising prevalence of obesity and type 2 diabetes is a global challenge. A possible mechanism linking insulin resistance and weight gain would be attenuation of insulin-evoked responses in brain areas relevant to eating in systemic insulin resistance. We measured brain glucose metabolism, using [(18)F]fluorodeoxyglucose positron emission tomography, in seven ...

Resistin was initially identified as a protein, secreted by adipocytes, which inhibits insulin action and adipose differentiation. The three proteins homologous to resistin were termed resistin-like molecules (RELM) alpha, beta and gamma. Resistin and RELMalpha are abundantly expressed in adipose, but RELMbeta and RELMgamma are secreted mainly from the gut. ...

BACKGROUND: Both obesity and diabetes are associated with an increased incidence of gallstones. Recent animal and human data from our laboratory suggest that insulin resistance is associated with increased gallbladder volume and/or impaired gallbladder emptying. Pioglitazone is a thiazolidinedione that has been shown to improve insulin resistance. Therefore, we tested ...

Insulin plays a key role in cognition and other aspects of normal brain function. Insulin resistance induces chronic peripheral insulin elevations, reduces insulin activity, and reduces brain insulin levels. The insulin resistance syndrome and associated conditions such as type 2 diabetes mellitus and hypertension, are associated with age-related memory impairment ...

Drugs that reverse insulin resistance are of importance as insulin resistance is frequently associated with type 2 diabetes. The three peroxisome proliferator-activated receptors (PPARs) PPARalpha, PPAR90 and PPARgamma are essential for the actions of the many insulin sensitizers. PPARalpha activation enhances free fatty acid oxidation and potentiates anti-inflammatory effects, while ...

Pregnancy is usually accompanied by insulin resistance; however, severe insulin resistance in pregnancy requiring massive doses of insulin is rare. We report a case of a 14-year-old with acanthosis nigricans and a strong family history of Type 2 diabetes who exhibited marked insulin resistance during pregnancy. Her treatment included terbutaline ...

It is recognised that obesity is a major driver for insulin resistance and Type 2 diabetes in both adult and young members of diverse societies. Weight loss strategies involving diet, exercise and behaviour modification work only for the minority of highly motivated individuals, but fail completely in the vast majority; ...

Endothelial dysfunction is regarded as an early stage of atherosclerosis, and plays a role in the development of atherosclerotic diseases. Insulin resistance is related to the atherosclerotic process. In this study, we examined the association between endothelial function and insulin resistance in 48 subjects with type 2 diabetes. In addition, ...

AIMS/HYPOTHESIS: Low birthweight is associated with insulin resistance and other insulin resistance-related phenotypes: diabetes, hypertension, and vascular disease in later life. The underlying mechanism is unclear. The foetal insulin hypothesis proposes that a single genetic predisposition to beta cell dysfunction/insulin resistance results in both reduced insulin-dependent foetal growth in utero, ...

Insulin resistance is not simply a problem of decreased glucose uptake in response to insulin, but a multifaceted syndrome that significantly increases the risk for cardiovascular disease. Insulin resistance is strongly associated with arterial hypertension and a pathogenetic role in the development of arterial hypertension has been suggested. One question ...

OBJECTIVE: To evaluate the interplay between hyperglycaemia, insulin resistance, hormones and adipokines in patients with type 2 diabetes mellitus (T2DM). DESIGN AND METHODS: Ten patients with T2DM with good glycaemic control (G), 10 with poor control (P) and 10 nondiabetic control subjects (C) were matched for sex (M/F 6/4), age ...

OBJECTIVE: The aim of this study was to evaluate whether adaptive responses made to the uterine or very early infant environment are affecting the current metabolic health of young children in the United Kingdom. METHODS: Participants were 300 healthy children and their parents from the EarlyBird Diabetes Study cohort. Children ...

Although the prevalence of cardiovascular complications is increased in insulin-resistant individuals, the underlying causes of this link have been elusive. Recent work suggests that several intracellular signal transduction pathways are inappropriately activated by hyperinsulinemia, hyperglycemia, increased free fatty acids, dyslipidemia, various inflammatory cytokines and adipokines--factors that are increased in insulin ...

The association of insulin resistance and body mass index (BMI) at age 13 years and change in insulin resistance and BMI from ages 13 to 19 years with systolic blood pressure, triglycerides, and high-density lipoprotein cholesterol at age 19 years was studied in black and non-Hispanic white children. Insulin clamps ...

Insulin resistance is considered a core component in the pathophysiology of the metabolic syndrome. Some clinicians measure serum insulin concentrations in the mistaken belief that they can be used to diagnose insulin resistance. Serum insulin levels are poor measures of insulin resistance. Furthermore, there is no clinical benefit in measuring ...

Type 2 diabetes, a growing global health problem, has a complex etiology involving many interactions between genetic and environmental factors. Essential to the development of the disease is insulin resistance of the peripheral tissues. Insulin resistance may be partly modified by the specific types of dietary fatty acids. Trans fatty ...

Previous characterization of mouse chromosome 2 identified genomic intervals that influence obesity, insulin resistance, and dyslipidemia. For this, resistant CAST/Ei (CAST) alleles were introgressed onto a susceptible C57BL/6J background to generate congenic strains with CAST alleles encompassing 67-162 Mb (multigenic obesity 6 [MOB6]) and 84-180 Mb (MOB5) from mouse chromosome ...

I expanded the population dynamics and genetics model published in 2005 by Crowder and Onstad to include larval survival and movement to evaluate the role of mixtures of transgenic and nontransgenic corn, Zea mays L., seed for resistance management of western corn rootworm. I studied both density-independent and density-dependent toxin ...

Fibrates, activators of the nuclear receptor PPARalpha, improve dyslipidemia, but their effects on insulin resistance and vascular disease are unresolved. To test the hypothesis that PPARalpha activation improves insulin resistance and vascular function, we determined the effects of fenofibrate in healthy adults with insulin resistance induced by short-term glucocorticoid administration. ...

Dairy intake has been inversely associated with insulin resistance, which may be partly due to the specific effects of calcium and magnesium. Data from the Insulin Resistance Atherosclerosis Study (1992-1999) for 1,036 US adults without diabetes at baseline were examined to evaluate the cross-sectional association of habitual dairy, magnesium, and ...

Insulin resistance is a state in which higher than normal concentrations of insulin are required for normal response. The most common underlying cause is central obesity, although primary insulin resistance in normal-weight individuals is also possible. Excess abdominal adipose tissue has been shown to release increased amounts of free fatty ...

Several factors that increase the risk of cardiovascular disease tend to cluster together in the same individual. Insulin resistance is believed to be a pathophysiological disturbance that underlies many of the risk factors. Whether insulin resistance per se is a cardiovascular risk factor is uncertain. Insulin resistance of myocardial muscle ...

The existence of links between Alzheimer's disease and diabetes is an important topic currently under active debate. Establishing such links if they exist and defining their common pathogenesis and pathophysiological mechanisms may lead to new concepts and research directions for the pharmacological treatment of Alzheimer's disease and diabetes. Alzheimer's disease ...

OBJECTIVE: To identify simple methods to estimate the degree of insulin resistance. RESEARCH METHODS AND PROCEDURES: The performance of a wide range of fasting-based index estimates of insulin sensitivity was compared by receiver operating characteristic analysis (area under curves and their 95% confidence intervals) against the M value from euglycemic ...

Insulin is a major regulatory hormone in glucose and fat metabolism, vascular function, inflammation, tissue remodeling, and the somatotropic axis of growth. Insulin resistance alters insulin signaling by decreasing insulin action in certain resistant pathways while increasing insulin signaling in other unaffected pathways via compensatory hyperinsulinemia. In humans, altered insulin ...

Considerable evidence supports the association between insulin resistance and vascular disease, and this has led to wide acceptance of the clustering of hyperlipidemia, glucose intolerance, hypertension, and obesity as a clinical entity, the metabolic syndrome. While insulin resistance, by promoting dyslipidemia and other metabolic abnormalities, is part of the proatherogenic ...

BACKGROUND: The association between elevated levels of triglycerides and insulin may be weaker in African-American women than in women of other groups, leading to underdiagnosis of the metabolic syndrome (MetS) in African-American women when using the National Cholesterol Education Program (NCEP) criteria, as that criteria does not include a marker ...

PURPOSE: Insulin resistance is thought to be a core defect in the pathophysiology of obesity-related comorbidities in children, such as type 2 diabetes. Exercise training is known to improve insulin resistance and reduce the risk of type 2 diabetes in adults. However, very little is known regarding the effects of ...

Obesity, diabetes, and hyperlipidemia are known risk factors for the development of gallstones. A growing body of animal and human data has correlated insulin resistance with organ dysfunction. The relationship among obesity, diabetes, hyperlipidemia, and abnormal gallbladder motility remains unclear. Therefore, we designed a study to investigate the association among ...

Since volatile allo-ocimene enhances resistance of Arabidopsis thaliana against Botrytis cinerea, we attempted to dissect the factors involved in this induced resistance. The penetration of B. cinerea hyphae into Arabidopsis epidermis and the growth of hyphae after penetration were suppressed on allo-ocimene-treated leaves. allo-Ocimene also induced lignification on cell walls ...

There is a major defect in skin blood flow (SkBF) in people with type 2 diabetes (T2DM). This defect is associated with relatively normal nitric oxide (NO) production in the skin. The abnormal blood flow cosegregates with hypertension, dyslipidemia, abnormal fatty acid composition, a proinflammatory state, and insulin resistance. Since ...

BACKGROUND: Insulin resistance has a causal role in type 2 diabetes. Serum levels of retinol-binding protein 4 (RBP4), a protein secreted by adipocytes, are increased in insulin-resistant states. Experiments in mice suggest that elevated RBP4 levels cause insulin resistance. We sought to determine whether serum RBP4 levels correlate with insulin ...

Endothelial dysfunction contributes to cardiovascular diseases that are also characterized by insulin resistance. Insulin resistance is a hallmark of metabolic disorders including Type 2 diabetes, obesity, and the metabolic syndrome that are also characterized by endothelial dysfunction. Metabolic actions of insulin to promote glucose disposal are augmented by vascular actions ...

Plasma homocysteine levels are elevated in individuals with type 2 diabetes contributing to the increased cardiovascular risk of these patients. As insulin resistance is a key feature in type 2 diabetic patients, hyperhomocysteinemia might be a consequence of insulin resistance. We studied this hypothesis in 839 individuals(male: 302, female: 537, ...

Peroxisome proliferator-activated receptors (PPARs) alpha and gamma are key regulators of lipid homeostasis and insulin resistance. In this study we show that a novel compound, 3-{4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-phenyl}- 2-[2-(2-nitro-phenoxy)-acetyl amino]-propionic acid (O325H), is an agonist with dual effect on PPARalpha/gamma by using dual-luciferase reporter gene assay. By activating PPARalpha and PPARgamma simultaneously, ...