The incretin hormone GLP-1 and mechanisms underlying its secretion

J Diabetes. 2016 Nov;8(6):753-765. doi: 10.1111/1753-0407.12439. Epub 2016 Aug 31.

Abstract

Glucagon-like peptide-1 (GLP-1) is a cell type-specific post-translational product of proglucagon. It is encoded by the proglucagon gene and released primarily from intestinal endocrine L-cells in response to hormonal, neuronal, and nutritional stimuli. In addition to serving as an incretin in mediating the effect of meal consumption on insulin secretion, GLP-1 exerts other functions in pancreatic islets, including regulation of β-cell proliferation and protection of β-cells against metabolic stresses. Furthermore, GLP-1 exerts numerous other functions in extrapancreatic organs, whereas brain GLP-1 signaling controls satiety. Herein we review the discovery of two incretins and the development of GLP-1-based drugs. We also describe the development of cellular models for studying mechanisms underlying GLP-1 secretion over the past 30 years. However, the main content of this review is a summary of studies on the exploration of mechanisms underlying GLP-1 secretion. We not only summarize studies conducted over the past three decades on elucidating the role of nutritional components and hormonal factors in regulating GLP-1 secretion, but also present a few very recent studies showing the possible role of dietary polyphenols. Finally, the emerging role of gut microbiota in metabolic homeostasis with the potential implication on GLP-1 secretion is discussed.

Keywords: L-cell models; L细胞模型; hormone secretion; incretins; microbiota; short-chain fatty acids; 微生物; 激素分泌; 短链脂肪酸; 肠促胰岛素.

Publication types

  • Review

MeSH terms

  • Animals
  • Glucagon-Like Peptide 1 / drug effects
  • Glucagon-Like Peptide 1 / metabolism*
  • Glucagon-Like Peptide 1 / physiology
  • Humans
  • Hypoglycemic Agents / chemistry
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use
  • Models, Biological

Substances

  • Hypoglycemic Agents
  • Glucagon-Like Peptide 1