Insulin resistance is a hallmark characteristic of type 2 diabetes. However, in healthy first-degree relatives of type 2 diabetics, insulin resistance is often present years before glucose intolerance or diabetes becomes clinically manifest. The mechanisms of insulin resistance involve conditions leading to an increased supply of fatty acids (e.g., high ...

An inappropriate glycogen accumulation in preeclamptic placentas was described as secondary to biochemical alterations. Insulin resistance is widely accepted to be associated with preeclampsia, although its basis remain unclear. A family of putative insulin mediators, namely inositol phosphoglycans, were described to exert many insulin-like effects on lipid and glucose metabolism. ...

PURPOSE: Insulin resistance, implying depressed cellular sensitivity to insulin, is a risk factor for type 2 diabetes and cardiovascular disease. This study is the first step towards the development of a technique of insulin resistance measurement in humans with a new tracer of glucose transport, [(123)I]6-deoxy-6-iodo-D-glucose (6DIG). METHODS: We investigated ...

Insulin has important vascular actions to stimulate production of nitric oxide from endothelium. This leads to capillary recruitment, vasodilation, increased blood flow, and subsequent augmentation of glucose disposal in classical insulin target tissues (e.g., skeletal muscle). Phosphatidylinositol 3-kinase-dependent insulin-signaling pathways regulating endothelial production of nitric oxide share striking parallels with ...

OBJECTIVE: To review MEDLINE literature for correlations between insulin resistance and erectile dysfunction (ED). DESIGN: MEDLINE literature review (1966 to present). SETTING: Academic medical center. PATIENT(S): None. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): None. RESULT(S): Erectile dysfunction affects more than half of men over the age of 40. Fortunately, most men ...

GSK3 has been implicated in the development of insulin resistance, primarily based on its role in regulation of glycogen synthesis. However, GSK3 is involved in many other important signaling cascades which may regulate glucose homeostasis and the development of insulin resistance. In addition, GSK3 is composed of two isoforms, GSK3alpha ...

In chronic myeloid leukemia (CML), resistance to imatinib is diverse. In addition to BCR-ABL-dependent mechanisms, BCR-ABL-independent mechanisms have been proposed. Here we established and characterized novel CML cell lines, an imatinib-sensitive cell line, MYL, and an imatinib-resistant subline, MYL-R. Treatment with imatinib inhibited phosphorylation of BCR-ABL and CrkL in both ...

Impaired insulin secretion and decreased insulin sensitivity are the main pathophysiologic features responsible for development of hyperglycemia in type 2 diabetes mellitus. Insulin resistance is often associated with increased adipose tissue mass. To examine which variables influence insulin sensitivity, we compared metabolic parameters, serum resistin, leptin, and adiponectin concentrations to ...

BACKGROUND: Aspirin therapy is a cornerstone in the prevention of atherothrombotic events, but recurrent vascular events are estimated to occur in 8-18% of patients taking aspirin for secondary prevention after 2 years. Estimates of biologic aspirin resistance vary from 5% to 60%, depending on the assay used. However, the relationship ...

Korean type 2 diabetics differ from Western diabetics in showing non-obese but centrally obese anthropometry and relatively more insulin secretory defects than insulin resistance. We assessed insulin secretion based on fasting serum C-peptide level and insulin resistance using the short insulin tolerance test (Kitt; rate constant for plasma glucose disappearance) ...

Endothelial dysfunction is reflected by an impaired nitric oxide (NO)-mediated vasodilatation. Insulin resistance may be linked to endothelial dysfunction by several mechanisms, including disturbances in signaling pathways common to both insulin action and NO production. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase, may contribute to endothelial dysfunction, and ...

OBJECTIVE: To test the hypothesis that short stature is associated with abdominal obesity, insulin resistance and lipid profile changes. METHODS: Anthropometric data were collected from 237 women (18-60 years old), residents of a shantytown in Maceió. Biochemical profiles of 60 individuals drawn from this population were determined. RESULTS: Total and ...

Although abnormal glucose metabolism defines type 2 diabetes mellitus (T2DM) and accounts for many of its symptoms and complications, efforts to understand the pathogenesis of T2DM are increasingly focused on disordered lipid metabolism. Here we review recent human studies exploring the mechanistic links between disorders of fatty acid/lipid metabolism and ...

Insulin resistance is a component of several health disorders, most notably impaired glucose tolerance and type 2 diabetes mellitus. Insulin-resistant individuals have an impaired biological response to the usual action of insulin; that is, they have reduced insulin sensitivity. Various methods are used to assess insulin sensitivity both in individuals ...

In order to better understand the impact of reduced mitochondrial function for the development of insulin resistance and cellular metabolism, human myotubes were established from lean, obese, and T2D subjects and exposed to mitochondrial inhibitors, either affecting the electron transport chain (Antimycin A), the ATP synthase (oligomycin) or respiratory uncoupling ...

There are many well-documented errors of metabolism involving genetic defects that affect carbohydrate utilization. The array of disorders includes the defective utilization of glucose, as well as enzymatic deficiencies in glycolysis and gluconeogenesis, and the pentose phosphate pathway. Besides, there is considerable literature about metabolic syndrome and diabetes. However, the ...

Insulin modulates cognition and other aspects of normal brain function. Insulin resistance is characterized by chronic peripheral insulin elevations, and it is accompanied by reduced brain insulin levels and insulin activity. Obesity, type 2 diabetes mellitus and hypertension are strongly associated with insulin resistance. In addition, insulin resistance increases the ...

Fatty liver is commonly associated with insulin resistance and type 2 diabetes, but it is unclear whether triacylglycerol accumulation or an excess flux of lipid intermediates in the pathway of triacyglycerol synthesis are sufficient to cause insulin resistance in the absence of genetic or diet-induced obesity. To determine whether increased ...

OBJECTIVE: We sought to assess insulin secretion/insulin resistance index in predicting the risk for future type 2 diabetes RESEARCH DESIGN AND METHODS: A total of 1,551 nondiabetic subjects from the San Antonio Heart Study received an oral glucose tolerance test (OGTT) with measurement of plasma glucose and insulin concentrations at ...

Anthropometric markers of obesity are simple means that may be used as markers of cardiovascular risk and insulin resistance. We compare body mass index, waist circumference and waist hip ratio as tools to screen for insulin resistance in 81 overweight Indigenous Australians using ROC curve analysis. Body mass index and ...

Elevated non-esterified fatty acids, triglyceride, diacylglycerol, and ceramide have all been associated with insulin resistance in muscle. We set out to investigate the role of intramyocellular lipid metabolites in the induction of insulin resistance in human primary myoblast cultures. Muscle cells were subjected to adenovirus-mediated expression of perilipin or incubated ...

Insulin resistance occurs in 20%-25% of the human population, and the condition is a chief component of type 2 diabetes mellitus and a risk factor for cardiovascular disease and certain forms of cancer. Herein, we demonstrate that the sphingolipid ceramide is a common molecular intermediate linking several different pathological metabolic ...

PURPOSE OF REVIEW: Dysregulation of free fatty acid metabolism is a key event responsible for insulin resistance and type 2 diabetes. According to the glucose-fatty acid cycle of Randle, preferential oxidation of free fatty acids over glucose plays a major role in insulin sensitivity and the metabolic disturbances of diabetes ...

Obesity-associated, system-wide elevations in free fatty acids, tumor necrosis factor alpha, and glucocorticoids increase intracellular lipid metabolites and promote insulin resistance. In this issue, Holland et al. (2007) provide pharmacological and genetic evidence that ceramide plays a key role in the development of insulin resistance induced by these factors.

Insulin resistance is a major causative factor for type 2 diabetes and is associated with increased risk of cardiovascular disease. Despite intense investigation for a number of years, molecular mechanisms underlying insulin resistance remain to be determined. Recently, chronic inflammation has been highlighted as a culprit for obesity-induced insulin resistance. ...

Insulin resistance, defined as an attenuated or inadequate response to a given amount of insulin, is associated with a wide variety of conditions including obesity, type 2 diabetes, essential hypertension, cardiovascular disease, polycystic ovary syndrome, non-alcoholic fatty liver, breast cancer, and acquired immune deficiency syndrome. Although pharmacological options for the ...

Tumour necrosis factor alpha (TNFalpha) is a pro-inflammatory cytokine which has been closely linked to obesity and insulin resistance. We present two cases of patients with rheumatoid arthritis (RA) and concomitant diabetes mellitus, who showed a marked decrease of fructosamine levels after initiating therapy with adalimumab, a TNFalpha-blocking agent, for ...

Illinoia pepperi (MacGillivray) infests cultivated highbush blueberries, Vaccinium corymbosum L., in the Northeastern United States. Allopatric resistance to I. pepperi was examined in Vaccinium darrowi Camp, which evolved in the absence of I. pepperi in the Southeastern U.S. V. corymbosum cv. "Elliott", was used as a susceptible control. Between population ...

Nonalcoholic fatty liver disease is strongly associated with hepatic insulin resistance and type 2 diabetes mellitus, but the molecular signals linking hepatic fat accumulation to hepatic insulin resistance are unknown. Three days of high-fat feeding in rats results specifically in hepatic steatosis and hepatic insulin resistance. In this setting, PKCepsilon, ...

AIMS/HYPOTHESIS: Levels of retinol binding protein (RBP4) are increased in the serum of insulin-resistant human subjects even before overt diabetes develops. RBP4 levels correlate with insulin resistance, BMI, WHR, dyslipidaemia and hypertension. Improvement of insulin sensitivity with exercise training is associated with reduction in serum RBP4 levels. Therefore serum RBP4 ...

Examination of individuals with 'extreme phenotypes' has revealed some rare monogenic disorders that were previously unknown. This identification can shed light on physiological pathways that are also important in normal physiology and how their impairment leads to more common, milder, multigenic forms of the disease. Ultimately, this is a potential ...

PURPOSE OF REVIEW: High levels of cardiorespiratory fitness and/or habitual physical activity are associated with reduced risk of cardiovascular disease. The responsible mechanisms are multifarious, but effects on insulin sensitivity are likely to play an important role. The purpose of this review is to highlight some recent evidence on the ...

Insulin resistance and erythrocyte sedimentation rate (ESR, a non-specific marker of inflammation) are known risk factors for cardiovascular disease. Although obesity is associated with increased ESR, it is unclear whether insulin resistance is associated with ESR in humans. The relationship between insulin resistance and ESR was studied in a cross-sectional, ...

Insulin resistance upregulates the renin-angiotensin system (RAS), which contributes to the pathogenesis of hypertension, heart failure, and atherosclerosis. RAS inhibition decreases cardiovascular and renal morbidity and mortality and the incidence of new-onset type 2 diabetes. To the same degree, angiotensin II impairs insulin signaling, induces inflammation via the nuclear factor-kappaB ...

OBJECTIVE: To determine some of the mechanisms involved in insulin resistance immediately following burn trauma, and to determine the efficacy of PPAR-alpha agonism for alleviating insulin resistance in this population. SUMMARY BACKGROUND DATA: Hyperglycemia following trauma, especially burns, is well documented. However, the underlying insulin resistance is not well understood, ...

The multifactorial nature of depression resembles that of other complex disorders such as diabetes mellitus or coronary artery disease. However, while for the latter disorders predisposing and risk factors have been identified, such knowledge is still scarce in depression. In this review we propose to use diabetes mellitus, for which ...

Insulin resistance is a primary component in the pathophysiology of type 2 diabetes. In latent autoimmune diabetes in adults (LADA), insulin resistance has been reported to be significantly lower than in autoantibody-negative type 2 diabetes (T2DM), but whether this might be related to differences in body mass index (BMI) has ...

The aim of this review was to investigate the possible causes and factors related to insulin resistance. The horse is a grazing animal but domestic horses are today sometimes fed large amounts of grains and concentrates rich in starch and sugars, which leads to an increased risk of developing insulin ...

The authors studied the frequency, distribution, and factors associated with prediabetes (fasting glucose, 100-125 mg/dL) in rural and urban children from San Luis Potosí, León, and Querétaro in central Mexico. Family history, somatometry, and levels of fasting insulin, glucose, and lipids were collected in 1238 children 6 to 13 years ...

Chronic kidney disease (CKD) is associated with complex metabolic changes including insulin resistance. Siew et al. have highlighted an important relationship between insulin resistance and skeletal muscle protein turnover. If insulin resistance is implicated in sarcopenia of CKD, further research will be required to determine whether interventions that improve insulin ...

Insulin resistance is associated with increased cardiovascular morbidity and mortality but the underlying mechanism(s) are incompletely understood. Epidemiological data suggest that insulin resistance and arterial stiffness are interrelated. In insulin sensitive-subjects, insulin acutely decreases the augmentation index as measured using pulse wave analysis. In insulin-resistant subjects, this effect of insulin ...

OBJECTIVE: To document a case of type B insulin resistance syndrome associated with systemic lupus erythematosus. METHODS: We present the clinical course of a female patient with type B insulin resistance syndrome, from the onset, diagnosis, and empiric treatment until remission of her disease. RESULTS: A 40-year-old African American woman ...

The increasing prevalence of obesity and diabetes mellitus in most industrialized countries, including China and India, is reaching epidemic proportions and requires intense studies and interventions. Insulin resistance appears to be the most relevant feature of the metabolic syndrome and is often the precursor of diabetes mellitus. Insulin resistance has ...

Extreme forms of insulin resistance are a rare cause of type 2 diabetes. However, individuals with severe insulin resistance pose unique diagnostic and therapeutic challenges, and have often acted as 'experiments of nature' providing important novel information regarding endocrine physiology and mechanistic insights relevant to the study of more common ...

In recent years, there has been an increasing prevalence of obesity and related diseases. This epidemiological change has increased the interest of researchers in the molecular and biochemical pathways involved in the pathogenesis of hepatic and biliary diseases. Insulin resistance is considered the major mechanism involved in the hepatic and ...

Insulin resistance is being recognized increasingly as the basis for the constellation of metabolic abnormalities that make up the metabolic syndrome, or Syndrome X. Insulin resistance is also the primary risk factor for the development of type 2 diabetes mellitus, which is currently reaching epidemic proportions by affecting more than ...

BACKGROUND: There are few data on the impact of insulin resistance on the recently defined categories of prehypertension (PHT) and prediabetes (PDM). The aim of this study was to examine associations of surrogate markers of insulin resistance with PHT/PDM. METHODS: Subjects included 554 individuals who underwent a 75-g oral glucose ...

Despite criticism regarding its clinical relevance, the concept of the metabolic syndrome improves our understanding of both the pathophysiology of insulin resistance and its associated metabolic changes and vascular consequences. Free fatty acids (FFA) and tumour necrosis factor-alpha (TNF-alpha) play prominent roles in the development of insulin resistance by impairing ...

Several recent studies have reported beneficial effects of pegvisomant monotherapy on glucose homeostasis for acromegalic patients resistant to somatostatin analogs (SSA). The aim of our longitudinal study was to test whether these beneficial effects on glucose homeostasis would also occur during combined pegvisomant + SSA treatment amongst partially SSA-resistant acromegalic ...

BACKGROUND: Studies have shown that metabolic syndrome and its consequent biochemical derangements in the various phases of diabetes may contribute to carcinogenesis. A part of this carcinogenic effect could be attributed to hyperinsulinism. High levels of insulin decrease the production of IGF-1 binding proteins and hence increase levels of free ...