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Diabetes Obes Metab. 2017 Sep;19 Suppl 1:22-29. doi: 10.1111/dom.12995.

β-Cell signalling and insulin secretagogues: A path for improved diabetes therapy.

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Division of Molecular and Metabolic Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
Division of Diabetes and Endocrinology, Kobe University Graduate School of Medicine, Kobe, Japan.


Insulin secretagogues including sulfonylureas, glinides and incretin-related drugs such as dipeptidyl peptidase 4 (DPP-4) inhibitors and glucagon-like peptide-1 receptor agonists are widely used for treatment of type 2 diabetes. In addition, glucokinase activators and G-protein-coupled receptor 40 (GPR40) agonists also have been developed, although the drugs are not clinically usable. These different drugs exert their effects on insulin secretion by different mechanisms. Recent advances in β-cell signalling studies have not only deepened our understanding of insulin secretion but also revealed novel mechanisms of insulin secretagogues. Clarification of the signalling mechanisms of the insulin secretagogues will contribute to improved drug therapy for diabetes.


Epac2A; KATP channel; glutamate; in silico similarity search; incretin; sulfonylurea; β-cell

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