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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)
CONTEXT Several studies suggest that genetic factors may play a role in the different responses to antidiabetic therapy; however, conclusive evidence is still lacking. OBJECTIVE The objective of the study was to investigate whether diabetic patients carrying the E23K variant in KCNJ11 are at increased risk for secondary sulfonylurea failure. DESIGN(More)
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)
AIMS/HYPOTHESIS A recent genome-wide association study identified the SLC30A8 rs13266634 polymorphism encoding an Arg325Trp polymorphism in the zinc transporter protein member 8 (ZnT-8) to be associated with type 2 diabetes. Here, we investigate whether the polymorphism is related to altered insulin release in response to intravenous and oral glucose loads(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)
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)
Insulin resistance plays a major role in dyslipidemia, cardiovascular disease, and type 2 diabetes. TRB3, a mammalian tribbles homolog, whose chromosomal region 20p13-p12 has been linked to human type 2 diabetes, impairs insulin signaling through the inhibition of Akt phosphorylation and is overexpressed in murine models of insulin resistance. We here(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)