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A genome-wide association study identifies novel risk loci for type 2 diabetes
Four loci containing variants that confer type 2 diabetes risk are identified and constitute proof of principle for the genome-wide approach to the elucidation of complex genetic traits. Expand
Islet beta cell failure in type 2 diabetes.
The major focus of this Review is on the mechanisms of islet beta cell failure in the pathogenesis of obesity-associated type 2 diabetes (T2D). As this demise occurs within the context of beta cellExpand
Isolation of INS-1-derived cell lines with robust ATP-sensitive K+ channel-dependent and -independent glucose-stimulated insulin secretion.
It is concluded that clonal selection of INS-1 cells allows isolation of cell lines that exhibit markedly enhanced and stable responsiveness to glucose and several of its known potentiators, which may be attractive new vehicles for studies of beta-cell function. Expand
Type 2 diabetes across generations: from pathophysiology to prevention and management
Evidence is emerging that a substantial part of diabetes susceptibility is acquired early in life, probably owing to fetal or neonatal programming via epigenetic phenomena, and maternal and early childhood health might, therefore, be crucial to the development of effective prevention strategies. Expand
Metabolic signaling in fuel-induced insulin secretion.
The current knowledge of the pathways involved in both positive and negative metabolic signaling for insulin secretion are reviewed and the role of established and candidate metabolic coupling factors are assessed, keeping recent developments in focus. Expand
Saturated fatty acids synergize with elevated glucose to cause pancreatic beta-cell death.
The data indicate that FFAs must be metabolized to long chain fatty acyl-CoA to exert toxicity, the effect of which can be reduced by activating fatty acid oxidation. Expand
AMP kinase and malonyl-CoA: targets for therapy of the metabolic syndrome
The hypothesis that a common feature linking these multiple abnormalities is dysregulation of the AMP-activated protein kinase (AMPK)/malonyl-CoA fuel-sensing and signalling network is reviewed. Expand
Glucagon-like peptide 1 induces pancreatic beta-cell proliferation via transactivation of the epidermal growth factor receptor.
The results are consistent with a model in which GLP-1 increases PI 3-kinase activity and enhances beta-cell proliferation via transactivation of the EGFR that would require the proteolytic processing of membrane-anchored BTC or other EGF-like ligands. Expand
Genetic variant near IRS1 is associated with type 2 diabetes, insulin resistance and hyperinsulinemia
The C allele of rs2943641 was associated with insulin resistance and hyperinsulinemia in 14,358 French, Danish and Finnish participants from population-based cohorts; this allele was also associated with reduced basal levels of IRS1 protein and decreased insulin induction of IRS 1-associated phosphatidylinositol-3-OH kinase activity in human skeletal muscle biopsies. Expand
Glucagon-like peptide-1 promotes DNA synthesis, activates phosphatidylinositol 3-kinase and increases transcription factor pancreatic and duodenal homeobox gene 1 (PDX-1) DNA binding activity in beta
The results suggest that glucagon-like peptide-1 may act as a growth factor for the beta cell by a phosphatidylinositol 3-kinase mediated event. Expand