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

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

Abstract

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.

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

Publication types

  • Review

MeSH terms

  • Animals
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Drugs, Investigational / adverse effects
  • Drugs, Investigational / pharmacology
  • Drugs, Investigational / therapeutic use*
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use*
  • Incretins / adverse effects
  • Incretins / pharmacology
  • Incretins / therapeutic use
  • Insulin / agonists*
  • Insulin / metabolism
  • Insulin Secretion
  • Insulin-Secreting Cells / drug effects*
  • Insulin-Secreting Cells / metabolism
  • Models, Biological*
  • Signal Transduction / drug effects*

Substances

  • Drugs, Investigational
  • Hypoglycemic Agents
  • Incretins
  • Insulin