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Type 2 diabetes is a heterogeneous and polygenic disorder resulting from interaction of genetic factors with environmental influences. Numerous candidate genes for insulin signaling proteins have been screened, but no single major susceptibility gene for type 2 diabetes has been identified. Due to its pivotal role in insulin action, the insulin receptor was(More)
BACKGROUND Hyperglycemia impairs functional properties of cytosolic and nuclear proteins via O-linked glycosylation modification (O-GlcNAcylation). We studied the effects of O-GlcNAcylation on insulin signaling in human coronary artery endothelial cells. METHODS AND RESULTS O-GlcNAcylation impaired the metabolic branch of insulin signaling, ie, insulin(More)
Insulin receptor substrate (IRS) molecules are key mediators in insulin signaling and play a central role in maintaining basic cellular functions such as growth, survival, and metabolism. They act as docking proteins between the insulin receptor and a complex network of intracellular signaling molecules containing Src homology 2 (SH2) domains. Four members(More)
It was reported that the common -866G/A polymorphism in the promoter of the human uncoupling protein-2 (UCP2) gene, which enhances its trascriptional activity, is associated with increased mRNA levels in human adipocytes and reduced risk of obesity. Studies in knockout mice and beta-cells indicate that UCP2 may play a role in beta-cell function. In this(More)
Molecular scanning of insulin receptor substrate-1 (IRS-1) revealed several amino acid substitutions. The most common IRS-1 variant, a Gly to Arg972 change, is more prevalent among type 2 diabetic patients. In this study we overexpressed wild-type and Arg972IRS-1 variant in L6 skeletal muscle cells and examined the functional consequences of this(More)
Insulin receptors (IR) and type 1 IGF receptors (IGF-IR) have been shown to form insulin/IGF-I hybrid receptors in tissues expressing both molecules. The biological function of hybrid receptors is still undefined. To date there is no information about the distribution of hybrid receptors in human tissues. We have applied two microwell-based immunoassays(More)
Obesity is frequently characterized by a reduced vitamin D bioavailability, as well as insulin-resistance and a chronic inflammatory response. We tested the hypothesis of an independent relationship between serum concentrations of 25-hydroxyvitamin D (25[OH]D) and several circulating inflammatory markers in a cohort of severely obese individuals.(More)
CONTEXT Hesperidin, a citrus flavonoid, and its metabolite hesperetin may have vascular actions relevant to their health benefits. Molecular and physiological mechanisms of hesperetin actions are unknown. OBJECTIVE We tested whether hesperetin stimulates production of nitric oxide (NO) from vascular endothelium and evaluated endothelial function in(More)
Diabetes and osteoporosis are common and complex disorders with an enormous health burden that can be often associated especially in middle-age and elderly individuals. Although there is raising awareness of the higher fractures rates among patients with type 1 (DM1) and 2 (DM2) diabetes, there are few data available on the pathogenetic mechanisms(More)
BACKGROUND Metabolic syndrome importantly accelerates the atherosclerotic process, the earliest event of which is endothelial dysfunction. Ghrelin, a gastric peptide with cardiovascular actions, has been shown to inhibit proatherogenic changes in experimental models. This study therefore investigated whether ghrelin administration might beneficially affect(More)