OBJECTIVE: Glucosamine (GlcN) is a popular nutritional supplement used to treat osteoarthritis in postmenopausal women. Postmenopausal women are at higher risk of type 2 diabetes mellitus and metabolic syndrome because of ovarian hormone deficiency. We used ovariectomized (OVX) rats as the model to investigate whether GlcN would induce insulin resistance ...

Aim: In the pathogenesis of diabetic retinopathy, retinal mitochondria are damaged, superoxide levels are elevated and mitochondrial DNA (mtDNA) biogenesis is impaired. MtDNA has a non-coding region, D-loop, which has essential transcription and replication elements, and this region is highly vulnerable to oxidative damage. The aim of this study is ...

Amino poly(glycerol methacrylate)s (PGOHMAs) were synthesized from linear or star-shaped poly(glycidyl methacrylate)s (PGMA)s via ring opening reactions with 1,2-ethanediamine, 1,4-butanediamine and diethylenetriamine, respectively. The resulting cationic polymers were employed to form polyelectrolyte complexes (PECs) with insulin. Parameters influencing complex formation were investigated by dynamic light scattering (DLS). PECs in the ...

BACKGROUND AND AIMS: Several studies have been carried out to characterize the different alterations associated with hypertriglyceridemia (HTG) and to identify this dyslipemia as an independent risk factor for cardiovascular disease (CVD). HTG is frequently, but not always, associated with insulin resistance (IR). The present study was aimed to evaluate ...

We conducted a three-stage genetic study to identify susceptibility loci for type 2 diabetes (T2D) in east Asian populations. We followed our stage 1 meta-analysis of eight T2D genome-wide association studies (6,952 cases with T2D and 11,865 controls) with a stage 2 in silico replication analysis (5,843 cases and 4,574 ...

We have examined the association of insulin receptors (IR) and downstream signaling molecules with membrane microdomains in rat basophilic leukemia (RBL-2H3) cells following treatment with insulin or tris(2-pyridinecarbxylato)chromium(III) (Cr(pic)(3)). Single-particle tracking demonstrated that individual IR on these cells exhibited reduced lateral diffusion and increased confinement within 100 nm-scale membrane compartments after ...

AIMS/HYPOTHESIS: Insulin resistance (IR) improves with weight loss, but this response is heterogeneous. We hypothesised that metabolomic profiling would identify biomarkers predicting changes in IR with weight loss. METHODS: Targeted mass spectrometry-based profiling of 60 metabolites, plus biochemical assays of NEFA, β-hydroxybutyrate, ketones, insulin and glucose were performed in baseline ...

Insulin resistance (IR) is a complex disorder caused by an interplay of both genetic and environmental factors. Recent studies identified a significant interaction between body mass index (BMI) and the rs1800795 polymorphism of the interleukin-6 gene that influences both IR and onset of type 2 diabetes mellitus, with obese individuals ...

Insulin, the primary hormone regulating the level of glucose in the bloodstream, modulates a variety of cellular and enzymatic processes in normal and diseased cells. Insulin signals are processed by a complex network of biochemical interactions which ultimately induce gene expression programs or other processes such as translation initiation. Surprisingly, ...

ABSTRACT: MicroRNAs (miRNAs) are a newly discovered type of small non-protein coding RNA that function in the inhibition of effective mRNA translation, and may serve as susceptibility genes for various disease developments. The SNP rs12416605, located in human type 1 diabetes IDDM10 locus, changes the seeding sequence (UGU[G/A]CCC) of miRNA ...

Recent evidence suggests that, after binding insulin, insulin receptors (IR) interact with specialized, cholesterol-containing, membrane microdomains and components of the actin cytoskeleton. Using single particle tracking techniques, we examined how binding of insulin, depletion of membrane cholesterol and disruption of actin filaments affect the lateral diffusion of individual quantum dot-labeled ...

Abstract Background: Increase in obesity and metabolic syndrome are associated with increases in insulin resistance (IR) and type 2 diabetes mellitus. Results from animal intervention studies and human epidemiological studies suggest that n-3 polyunsaturated fatty acids can prevent and reverse IR, but results from human intervention studies have varied. Results ...

Background: Insulin resistance (IR) is associated with a higher risk of multiple diseases and its early detection would allow to minimize the associated risk; the presence of acanthosis nigricans (AN) it´s associated to the presence of IR. Objective: To evaluate the sensibility and specificity of AN to diagnose IR in ...

Objective: The objective of this paper is to detect the incidence of insulin resistance (IR) in Chronic Kidney disease (CKD) patients and the presence of impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and diabetes mellitus (DM) in patients with/without IR. Methods: We enrolled 113 patients with CKD. Biochemical parameters were ...

Genome-wide association studies provide information implicating 5,10-methenyltetrahydrofolate synthetase (MTHFS) as a candidate gene for renal disease. In the Atherosclerosis Risk in Communities study, the intronic single-nucleotide polymorphism rs6495446 in the gene MTHFS confirmed the association between this gene and renal disease among Caucasian participants. We replicated this genetic association in ...

The relative expression patterns of the two insulin receptor isoforms, +/- exon11 (IR-B/A respectively), are tissue dependent. Therefore we have developed insulin analogues with different binding affinities for the two isoforms, to test whether tissue-preferential biological effects can be attained. In rats and mice, IR-B is the most prominent isoform ...

The aim of this study was to investigate whether cap-independent insulin mRNA translation occurs in human pancreatic islets at basal conditions, during stimulation at a high glucose concentration and at conditions of nitrosative stress. We also aimed at correlating cap-independent insulin mRNA translation with binding of the IRES transacting factor ...

Insulin resistance (IR) is the major feature of metabolic syndrome, including type 2 diabetes. IR studies are mainly focused on peripheral tissues, such as muscle and liver. There is, however, little knowledge about IR in neurons. In this study, we examined whether neurons develop IR in response to hyperinsulinemia. We ...

MicroRNAs are short noncoding RNAs that usually reduce translation of messenger RNAs. Changes in microRNA-192 (miR-192) are reported in states of renal fibrosis. New evidence supports a role for miR-192 and its target miR-200b/c in transforming growth factor-β1 regulation of its own expression and that of collagens in mesangial cells, ...

The aim of the study was to assess the association of Insulin Resistance [IR] assessed by Homeostasis Assessment model (HOMA-IR) with cardiovascular risk factors in subjects with Normal Glucose Tolerance [NGT] in Asian Indians. This cross-sectional study recruited subjects from the Chennai Urban Rural Epidemiology Study [CURES] an epidemiological study ...

OBJECTIVE: To investigate the correlation between serum visfatin and insulin resistance (IR) in non-diabetic essential hypertensive (EH) patients with and without IR, and to evaluate the effect of antihypertensive treatment on serum visfatin and IR in these patients. METHODS: A total of 81 non-diabetic EH patients, including 54 with IR ...

Retinol-binding protein 4 (RBP4) is an adipokine proposed to be specifically associated with insulin resistance (IR). We examined whether serum levels of RBP4 were associated with IR in pregnancy. One hundred seventy-two women with gestational diabetes mellitus (GDM) and 361 pregnant Thai women who did not have GDM but had ...

The clustering of cardiovascular risk factors is termed the metabolic syndrome (MS), which strongly predict risk of diabetes and cardiovascular disease. Many studies implicate insulin resistance (IR) in the development of diabetes, but ignore the contribution of beta-cell dysfunction. Hence, we studied beta-cell function, as assessed by HOMA model, in ...

Type 2 diabetes prevalence is increasing worldwide. Treatments are available, but glycaemic control is not always effective in many patients. Better models are needed to create new and improved therapies and to expand our understanding of how type 2 diabetes begins and progresses. Translational research involves the transformation of knowledge ...

Aims:  Several polymorphisms of the melatonin receptor 1B gene (MTNR1B) have been shown to be associated with elevated fasting plasma glucose and impaired early insulin release. The aim of this study was to assess the effects of MTNR1B variants on traits related to the metabolic syndrome in the self-contained population of ...

Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of insulin receptor (IR) activation and glucose homeostasis, but the precise molecular mechanisms governing PTP1B substrate selectivity and the regulation of insulin signaling remain unclear. Here we have taken advantage of Drosophila as a model organism to establish the role of ...

ETHNOPHARMACOLOGICAL RELEVANCE: The use of an aqueous extract of coriander (Coriandrum sativum L.; Apiaceae, Umbelliferae) seeds (CS-extract) in Moroccan traditional treatment of diabetes remains to be experimentally validated. AIM OF THE STUDY: The study aim was to investigate potential hypoglycemic (and hypolipidemic) activity of CS-extract after a single oral dose ...

Pancreatic beta cell dysfunction and reduced insulin sensitivity are fundamental factors associated with glucotoxicity, lipotoxicity and oxidative stress in type 2 diabetic patients (T2DM). Diabetic milieu can induce apoptosis in several types of cells. The aim of present study was to compare circulating soluble apoptotic markers (sFas and sFas-L) with ...

ABSTRACT: BACKGROUND: Obstructive sleep apnea (OSA) is associated with obesity, insulin resistance (IR) and diabetes. Continuous positive airway pressure (CPAP) rapidly mitigates OSA in obese subjects but its metabolic effects are not well-characterized. We postulated that CPAP will decrease IR, ghrelin and resistin and increase adiponectin levels in this setting. ...

The TyG index was evaluated as a surrogate method for estimation of insulin resistance (IR). TyG index correlated with adiposity, metabolic and atherosclerosis markers related to IR and presented a moderate degree of agreement with hyperglycemic clamp. TyG index represents an accessible tool for assessment of IR in clinical practice.

It has proven to be challenging to isolate the genes underlying the genetic component conferring susceptibility to type 1 and type 2 diabetes. Unlike previous approaches, 'genome wide association studies' (GWAS) have extensively delivered on the promise of uncovering genetic determinants of complex disease, with a number of novel disease-associated ...

Insulin-mediated glucose uptake in insulin target tissues is correlated with interstitial insulin concentration, rather than plasma insulin concentration. Therefore, insulin delivery to the interstitium of target tissues is very important, and the endothelium may also play an important role in the development of insulin resistance. After treating bovine aortic endothelial ...

Prolyl hydroxylase domain 2 (PHD2) has been implicated in several pathways of cell signaling, most notably in its regulation of hypoxia-inducible factor (HIF)-1α stability. In normoxia, PHD2 hydroxylates proline residues on HIF-1α, rendering it inactive. However, in hypoxia, PHD2 is inactive, HIF-1α is stabilized and downstream effectors such as vascular ...

Glucokinase regulatory protein (GCKR) regulates the trafficking and enzymatic activity of hepatic glucokinase, the rate-limiting enzyme in glycogen synthesis and glycolysis. The intronic single-nucleotide polymorphism (SNP) rs780094 (intron 16) and the missense SNP rs1260326 (P446L) in the GCKR gene are strongly associated with increased circulating triglyceride and C-reactive protein levels ...

We compared insulin and IGF effects in adipocytes expressing IR (insulin receptors), and preadipocytes expressing IR and IGF-IR (IGF-I receptors). Treatment of adipocytes with insulin, IGF-II or IGF-I resulted in phosphorylation of IR. Order of potency was insulin>IGF-II>IGF-I. In preadipocytes IR, IGF-IR and insulin/IGF-I hybrid receptors (HR) were detected. Treatment ...

Genome wide association analyses have revealed large numbers of common variants influencing predisposition to type 2 diabetes and related phenotypes. These studies have predominantly featured European populations, but are now being extended to samples from a wider range of ethnic groups. The transethnic analysis of association data is already providing ...

Low circulating testosterone concentrations have been associated with insulin resistance (IR). Androgen action is mediated by the androgen receptor (AR) whose activity is modulated by a polymorphic CAG repeat sequence within exon 1. An interaction between testosterone and CAG repeat length (CAG length) with respect to IR has been described ...

Objective Diabetic retinopathy is a leading cause of blindness. The purpose of this study is to identify novel genetic loci associated with the sight threatening complications of diabetic retinopathy. Research Design and Methods We performed a meta-analysis of genome-wide association data for severe diabetic retinopathy as defined by diabetic macular ...

ABSTRACT: Despite years of investigation, very little is known about the genetic predisposition for gestational diabetes mellitus (GDM). However, the advent of genome-wide association and identification of loci contributing to susceptibility to type 2 diabetes mellitus has opened a small window into the genetics of GDM. More importantly, the study ...

AIMS/HYPOTHESIS: Hyperaminoacidaemia attenuates glucose disposal during hyperinsulinaemic clamps in healthy lean individuals, an effect thought to be mediated by negative feedback on insulin signalling, downstream of the mammalian target of rapamycin (mTOR) signalling pathway. This has been interpreted as amino acids causing insulin resistance in healthy people, and contributing to ...

Summary Background Insulin resistance (IR) is highly prevalent in chronic hemodialysis (CHD) patients and is associated with poor cardiovascular outcomes. Hyperinsulinemic euglycemic glucose clamp (HEGC) is the gold standard for measuring IR. The comparison of commonly-used indirect indices of IR to HEGC has not been adequately performed in this population. ...

Insulin is the key regulator of Glucose homeostasis in mammals and glucose stimulated insulin biosynthesis is essential for maintaining glucose levels in a narrow range in mammals. Glucose specifically promotes the translation of insulin in pancreatic β-islet, and the untranslated regions of insulin mRNA play a role in such regulation. ...

Although the importance of adipose tissue (AT) glucose transport in regulating whole-body insulin sensitivity is becoming increasingly evident and insulin resistance (IR) has been widely recognized, the underlying mechanisms of IR are still not well understood. The purpose of the present study was to determine the early pathological changes in ...

OBJECTIVE: The goal of this study was to examine the effect of insulin resistance (IR) in subjects without diabetes on the relationship of a dyslipidemia with high triglycerides and low high-density lipoprotein cholesterol (HDL-C) to the development of coronary heart disease (CHD). METHODS AND RESULTS: Lower and higher fasting plasma ...

Insulin signaling comprises a complex cascade of events, playing a key role in the regulation of glucose metabolism and cellular growth. Impaired response to insulin is the hallmark of diabetes, whereas upregulated insulin activity occurs in many cancers. Two splice variants of the insulin receptor (IR) exist in mammals: IR-A, ...

Recent advances in genetic analysis have enabled researchers to perform genome-wide surveys for common DNA sequence variants associated with risk of Type 2 diabetes and related traits. Over the past 4 years, these endeavours have extended the number of proven Type 2 diabetes-susceptibility loci from a handful to the current ...

Acute inflammation in humans is associated with transient insulin resistance (IR) and dyslipidemia. Chronic low-grade inflammation is a pathogenic component of IR and adipose tissue dysfunction in obesity-induced type 2 diabetes. Because feline diabetes closely resembles human type 2 diabetes, we studied whether lipopolysaccharide (LPS)-induced subacute inflammation, in the absence ...

Early detection of reduced insulin sensitivity (IS) and insulin resistance (IR) is desirable. The aim here was to evaluate correlations of anthropometric indicators for identifying IR or IS and determine the cutoff points of the most effective indicators. Cross-sectional study in the city of São Paulo. Sixty-one individuals with normal ...

Honeybee workers are essentially sterile female helpers that make up the majority of individuals in a colony. Workers display a marked change in physiology when they transition from in-nest tasks to foraging. Recent technological advances have made it possible to unravel the metabolic modifications associated with this transition. Previous studies ...

Food-derived peptides, specifically those derived from milk, may adversely affect health by increasing the risk of insulin-dependent diabetes. This position is based on the relationship of type 1 diabetes (T1D) and the consumption of variants A1 and B β-casein from cow's milk. It appears that β-casomorphin-7 (BCM-7) from β-casein may ...