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BACKGROUND Unlike most antihyperglycaemic drugs, glucagon-like peptide-1 (GLP-1) receptor agonists have a glucose-dependent action and promote weight loss. We compared the efficacy and safety of liraglutide, a human GLP-1 analogue, with exenatide, an exendin-based GLP-1 receptor agonist. METHODS Adults with inadequately controlled type 2 diabetes on(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)
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)
IMPORTANCE Diabetes is associated with an elevated risk of coronary heart disease (CHD). Previous studies have suggested that the genetic factors predisposing to excess cardiovascular risk may be different in diabetic and nondiabetic individuals. OBJECTIVE To identify genetic determinants of CHD that are specific to patients with diabetes. DESIGN,(More)
OBJECTIVE To evaluate efficacy and safety of switching from twice-daily exenatide to once-daily liraglutide or of 40 weeks of continuous liraglutide therapy. RESEARCH DESIGN AND METHODS When added to oral antidiabetes drugs in a 26-week randomized trial (Liraglutide Effect and Action in Diabetes [LEAD]-6), liraglutide more effectively improved A1C,(More)
Transglutaminase 2 (TGase 2) is a Ca+2-dependent enzyme that catalyzes both intracellular and extracellular cross-linking reactions by transamidation of specific glutamine residues. TGase 2 is known to be involved in the membrane-mediated events required for glucose-stimulated insulin release from the pancreatic beta cells. Here we show that targeted(More)
Evidence suggests that nonalcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are associated with an increased risk of chronic kidney disease (CKD). In this study we aimed to evaluate whether the severity of liver fibrosis estimated by NAFLD fibrosis score is associated with higher prevalence of CKD in individuals with NAFLD. To(More)
—It has been suggested that serine (Ser) phosphorylation of insulin receptor substrate-1 (IRS-1) decreases the ability of IRS-1 to be phosphorylated on tyrosine, thereby attenuating insulin signaling. There is evidence that angiotensin II (AII) may impair insulin signaling to the IRS-1/phosphatydilinositol 3-kinase (PI 3-kinase) pathway by enhancing Ser(More)
OBJECTIVE Type 2 diabetes and essential hypertension are major risk factors for cardiovascular diseases. Endothelial dysfunction is an early step in the development of atherosclerosis and has been demonstrated in hypertensive and diabetic patients. RESEARCH DESIGN AND METHODS We designed this study to determine whether forearm endothelial dysfunction is(More)