BACKGROUND: Thiazolidinediones (TZDs) are oral antihyperglycemic drugs that are used to treat insulin resistance. Rosiglitazone is a TZD that has been found to increase the risk of cardiovascular events, especially of myocardial ischemic events. OBJECTIVE: The aim of this study was to conduct a direct comparison of TZDs (pioglitazone and ...

Insulin resistance is the most important pathophysiological feature in many pre-diabetic states. Type 2 diabetes mellitus is a complex metabolic disease and its pathogenesis involves abnormalities in both peripheral insulin action and insulin secretion by pancreatic β-cells. The creation of monogenic or polygenic genetically manipulated mice models in a tissue-specific ...

The selenoprotein S (SELS) is a putative receptor for serum amyloid A, and recent studies have suggested that SELS may be a link between type 2 diabetes mellitus and inflammation. Genetic studies of SELS polymorphisms have revealed associations with circulating levels of inflammatory markers and hard end points of cardiovascular ...

Adipose tissue is a highly dynamic endocrine organ, secreting a number of bioactive substances (adipokines) regulating insulin sensitivity, energy metabolism and vascular homeostasis. Dysfunctional adipose tissue is a key mediator that links obesity with insulin resistance, hypertension and cardiovascular disease. Obese adipose tissue is characterized by adipocyte hypertrophy and infiltration ...

In this article, we discuss inflammation associated with adipose tissue dysfunction as a potential link with obesity-related insulin resistance, and how obesity-related inflammatory components, such as immune cells, cytokines/chemokines and adipocytokines, induce obesity-related pathologies.

Context: Autophagy is a housekeeping mechanism, involved in metabolic regulation and stress response, shown recently to regulate lipid droplets biogenesis/breakdown and adipose tissue phenotype. Objective: We hypothesized that in human obesity autophagy may be altered in adipose tissue in a fat depot and distribution-dependent manner. Setting and Patients: Paired omental ...

In obesity, adipocyte hypertrophy and chronic inflammation in adipose tissues cause insulin resistance and type-2 diabetes. Trigonella foenum-graecum (fenugreek) can ameliorate hyperglycemia and diabetes. However, the effects of fenugreek on adipocyte size and inflammation in adipose tissues have not been demonstrated. In this study, we determined the effects of fenugreek ...

Obesity and diabetes mellitus (DM) are established risk factors for the development of chronic kidney disease. Visceral adiposity (VAT) and subcutaneous adiposity (SAT) may be associated with the differential metabolic risk. Our study was performed to determine whether VAT or SAT was associated with the decrease of renal function in ...

Peroxisome proliferator-activated receptor-γ (PPARγ) ligands, including the insulin-sensitizing thiazolidinedione drugs, transcriptionally regulate hundreds of genes. Little is known about the relationship between PPARγ ligand-specific modulation of cellular mechanisms and insulin sensitization. We characterized the insulin sensitivity and multitissue gene expression profiles of lean and insulin-resistant, obese Zucker rats untreated or ...

Plasma YKL-40 is elevated in patients with type 2 diabetes. The potential role of visceral adipose tissue (VAT) as a significant source of YKL-40 is unknown. In the study circulating and expression levels of YKL-40 were examined in VAT analyzing the contribution of adipocytes and stromovascular fraction cells (SVFCs). We ...

Fasting and post-prandial abnormalities of adipose tissue (AT) lipoprotein lipase (LPL) and hormone- sensitive lipase (HSL) activities may have pathophysiological relevance in insulin-resistant conditions. The aim of this study was to evaluate activity and gene expression of AT LPL and HSL at fasting and 6 h after meal in two ...

The increased incidence of both type 2 diabetes mellitus and obesity has prompted the need to develop physiologically relevant adipose tissue models for controlled study of both normal and diseased adipose functions. Insulin resistance, characteristic of both type 2 diabetes mellitus and obesity, is often preceded by hyperinsulinemia. We propose ...

Obesity is endemic in many regions of the world and a forerunner of several serious and sometimes fatal diseases such as ischemic heart disease, stroke, kidney failure and neoplasia. Although we know its origin--it results when energy intake exceeds energy expenditure--at present, the only proven therapy is bariatric surgery. This ...

In addition to decreased insulin sensitivity, diabetes is a pathological condition associated with increased inflammation. The ω-3 fatty acids have been proposed as anti-inflammatory agents. Thus, the major goal of this study was to analyze the effects of fatty acid supplementation on both insulin sensitivity and inflammatory status in an ...

Objective. This study is conducted on a model of insulin-resistant (IR) mice born to dams which were rendered diabetic by the administration of streptozotocin. Methods. Adult IR and control offspring were selected and we determined the mRNA expression of transcription factors known to modulate pancreatic and adipose tissue activities and ...

Altered body composition has been suggested as a major factor for the high prevalence of impaired glucose tolerance, insulin resistance, and dyslipidemia in individuals with spinal cord injury (SCI). The contributions of visceral adipose tissue (VAT), trunk subcutaneous adipose tissue (SAT), and the VAT/SAT ratio to these metabolic derangements in ...

To explore the metabolic actions of nifedipine on diabetes, we examined glucose intolerance and white adipose tissue changes in type 2 diabetic KK-A(y) mice. Male KK-A(y) mice were treated with nifedipine (1.5 mg/kg/day in lab chow) for 5 weeks, which did not affect blood pressure or feeding of KK-A(y) mice. ...

Type 2 diabetes is associated with numerous long-term complications. This study aims to investigate whether impaired function of tissue-resident multipotent cells play role in pathogenesis of allied complications. Adipose-tissue-derived mesenchymal stem cells (ASCs) derived from nondiabetic (nASCs) and diabetic (dASCs) donors were compared with regard to glucose metabolism, cell replication, ...

Physical inactivity is a risk factor for type 2 diabetes and may be more detrimental in first-degree relative (FDR) subjects, unmasking underlying defects of metabolism. Using a positive family history of type 2 diabetes as a marker of increased genetic risk, the aim of this study was to investigate the ...

Obesity has now reached pandemic proportions leading to a collection of morbidities referred to as metabolic syndrome including insulin resistance, type 2 diabetes and cardiovascular disease. The expansion of adipose tissue is a direct cause of these comorbidities due to excessive accumulation of triglycerides within adipocytes, causing disruption of normal ...

In recent years, it has become widely accepted that obesity is characterized by a chronic low-grade inflammation of adipose tissue that predisposes affected individuals to insulin resistance, Type 2 diabetes and other disorders associated with the metabolic syndrome. On the other hand, a subset of obese individuals appears to be ...

Curcuma longa (turmeric) has been used widely as a spice, particularly in Asian countries. It is also used in the Ayurvedic system of medicine as an antiinflammatory and antimicrobial agent and for numerous other curative properties. The aim of this study was to investigate the effects of an aqueous extract ...

The current study tested the hypothesis that glucose utilization differs between visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT), and investigated potential mechanisms for such a finding. VAT burden correlates better with cardiovascular risk than does SAT burden. Beyond volumetric measurement, glucose uptake in adipose tissue (AT) might reflect ...

The widespread epidemics of obesity and type 2 diabetes mellitus (T2DM) suggest that both conditions are closely linked. An increasing body of evidence has shifted our view of adipose tissue from a passive energy depot to a dynamic "endocrine organ" that tightly regulates nutritional balance by means of a complex ...

Adipose tissue normally has low glycerol kinase activity, but its expression is enhanced under conditions of augmented insulin sensitivity and/or obesity. Since these conditions occur during early pregnancy, the comparative utilization of glucose or glycerol by isolated adipocytes from rats at 0, 7, 14, or 20 days of pregnancy was ...

Common obesity and inherited lipodystrophies, rare disorders characterized by a partial (familial partial lipodystrophy; FPLD) or complete (congenital generalized lipodystrophy; CGL) lack of adipose tissue, are both associated with metabolic complications such as insulin resistance and type 2 diabetes. Mutations in the transcription factor peroxisome proliferator activated receptor (PPAR)γ and ...

In obesity, particularly increased visceral- (VAT), but not total (TAT) adipose tissue mass is a major source of proinflammatory cytokine expression and secretion. VAT, more than TAT, is associated with endothelial dysfunction (ED), which is an accepted risk factor for atherosclerosis. Consequently, we hypothesized that during a lifestyle intervention specifically ...

The renin-angiotensin system affects insulin sensitivity mainly through the angiotensin II type 1 receptor. In this study, the effects of renin inhibition on insulin resistance and adipose tissue dysfunction were explored in type 2 diabetic KK-A(y) mice. Male KK-A mice were treated with a direct renin inhibitor, aliskiren, administered subcutaneously ...

BACKGROUND: Insulin resistance has been associated with risk of laminitis in horses. Genes coding for proinflammatory cytokines and chemokines are expressed more in visceral adipose tissue than in subcutaneous adipose tissue of insulin-resistant (IR) humans and rodents. HYPOTHESIS/OBJECTIVES: To investigate adipose depot-specific cytokine and chemokine gene expression in horses and ...

Inhibitors of 11β-HSD1 are in clinical trials for the treatment of type 2 diabetes. These compounds act by decreasing the cortisol generated in liver and adipose tissue, and therefore reducing tissue-specific gluconeogenesis and fatty acid metabolism. However, there is concern that reduction in tissue-regenerated cortisol might decrease feedback to the ...

Visceral adiposity is more strongly linked to insulin resistance than subcutaneous adiposity. High insulin levels can be mitogenic or adipogenic to adipocytes, but little is known regarding these effects of insulin on stromal cells from visceral and subcutaneous fat depots. Consequently, we measured adipogenesis and mitosis in response to elevated ...

Increased body fat correlates with the enlargement of average fat cell size and reduced adipose tissue insulin sensitivity. It is currently unclear whether adipocytes, as they accumulate more triglycerides and grow in size, gradually become less insulin sensitive or whether obesity-related factors independently cause both the enlargement of adipocyte size ...

Adipose tissue secretes proteins referred to as adipokines, many of which promote inflammation and disrupt glucose homeostasis. Here we show that secreted frizzled-related protein 5 (Sfrp5), a protein previously linked to the Wnt signaling pathway, is an anti-inflammatory adipokine whose expression is perturbed in models of obesity and type 2 ...

This study explores whether the relationship between lower socioeconomic status and insulin resistance in adolescents is mediated by both physiological and psychological factors associated with increased cardiometabolic risk. School-based longitudinal cohort study of 1222 healthy, non-Hispanic black and white teens. Parent education (PE), youth-specific Cook-Medley hostility scale, waist circumference, height, ...

Chronic low-grade inflammation is a feature of obesity and is postulated to be causal in the development of insulin resistance and type 2 diabetes. The aim of this study was to assess whether overfeeding induces peripheral insulin resistance in lean and overweight humans, and, if so, whether it is associated ...

Acidosis modulates physiologic and pathophysiologic processes but the mechanism of acidotic vasodilatation remains unclear. We therefore explored this in aortic rings from normal and streptozotocin-induced diabetic Sprague-Dawley rats. Phenylephrine (PE)-induced contraction in endothelium-intact and -denuded rings were recorded under normal and acidotic pH with or without drug probes. Acidosis exerted ...

Based on its role as an energy storage compartment and endocrine organ, white adipose tissue (WAT) fulfills a critical function in the maintenance of whole-body energy homeostasis. Indeed, WAT dysfunction is connected to obesity-related type 2 diabetes triggered at least partly by an inflammatory response in adipocytes. The pseudokinase tribbles ...

Obesity is a strong risk factor for resistance to insulin-mediated glucose disposal, a precursor of type 2 diabetes and other disorders. However, not all obese individuals are insulin resistant. We sought to identify the molecular pathways that might cause obesity-associated insulin resistance in humans by studying the morbidly obese who ...

The aim of this study was to measure 11β-HSD-1 activity in subcutaneous adipose tissue by an ex vivo method in three subgroups; lean, obese, and type 2 diabetes subjects, both in the fasting state and after a mixed meal and to determine the variability and reproducibility of this method. Eighteen ...

PFKFB3 is the gene that codes for the inducible isoform of 6-phosphofructo-2-kinase (iPFK2), a key regulatory enzyme of glycolysis. As one of the targets of peroxisome proliferator-activated receptor gamma (PPARgamma), PFKFB3/iPFK2 is up-regulated by thiazolidinediones. In the present study, using PFKFB3/iPFK2-disrupted mice, the role of PFKFB3/iPFK2 in the anti-diabetic effect ...

OBJECTIVE: The objective of the study was to assess the effect of high aldosterone levels on insulin sensitivity of adipose tissue in humans. METHODS: Visceral adipose tissue (VAT) was obtained from patients with aldosterone-producing adenoma (APA; n=14) and, as controls, nonfunctioning adenoma (NFA; n=14) undergoing laparoscopic adrenalectomy. Homeostasis model assessment ...

CONTEXT AND OBJECTIVE: Subcutaneous adipose tissue (SAT) lipoatrophy (LA) is a rare complication of insulin therapy. We aimed to analyze the ultrastructural and molecular aspects of LA lesions. SETTING AND PATIENTS: Macroscopic and microscopic morphology of SAT beneath the LA areas from patients with type 1 diabetes treated with Lispro ...

Adipose tissue in obese individuals is characterized by reduced capillary density and reduced oxygenation. Our objective was to test whether hypoxia is associated with reduced antilipolytic effect of insulin. PARTICIPANTS, DESIGN, AND SETTING: Twenty-one lean and obese individuals participated in this cross-sectional study at a university-based clinical research center. In ...

Orosomucoid (ORM), also called alpha-1 acid glycoprotein, is an abundant plasma protein that is an immunomodulator induced by stressful conditions such as infections. In this study, we reveal that Orm is induced selectively in the adipose tissue of obese mice to suppress excess inflammation that otherwise disturbs energy homeostasis. Adipose ...

Type 2 diabetes mellitus and obesity are the most frequent endocrine-metabolic diseases in the world and their pathogenic basis are characterized by insulin resistance and insulin secretion defects that can be demonstrated through several alterations in carbohydrates, lipids, and protein metabolism. The peroxisome proliferator-activated receptors have been identified as key ...

Hyperglycaemia initiates endothelial dysfunction causing diabetic macro- and micro-vasculopathy, the main causes of morbidity and mortality in diabetes mellitus. The vasculopathy exhibits gender peculiarities. We therefore explored gender differences in comparing the effects of hyperglycaemia (50 mM) per se with its hyperosmolar (50 mM) effects on vascular tissue responses to ...

A major component of obesity-related insulin resistance is the establishment of a chronic inflammatory state with invasion of white adipose tissue by mononuclear cells. This results in the release of pro-inflammatory cytokines, which in turn leads to insulin resistance in target tissues such as skeletal muscle and liver. To determine ...

Diabetes mellitus (DM) is associated with increased risk of reproductive problems. Estrogens have important roles in reproductive processes in both genders. Aromatase catalyzes the conversion of androgens to estrogens and is expressed in a variety of tissues. Although it is known that insulin regulate the activity of aromatase, there are ...

Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a nuclear receptor that functions as a master transcriptional regulator of adipocyte conversion. During PPARgamma transactivation, multiple signaling pathways interact with one another, leading to the differentiation of both white and brown adipose tissue. Ligand activation of the PPARgamma-RXR heterodimer complex also enhances insulin sensitivity, ...

Metabolic abnormalities underlying diabetes can be abrogated by L-arginine. Here we examined the molecular basis of disturbed interscapular brown adipose tissue (IBAT) thermogenesis and the possible role of nitric oxide (NO) in the IBAT of diabetic rats. To induce diabetes, adult Mill Hill hybrid hooded male rats were given a ...