Mechanisms underlying glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 secretion

J Diabetes Investig. 2016 Apr;7 Suppl 1(Suppl 1):13-9. doi: 10.1111/jdi.12478. Epub 2016 Mar 14.

Abstract

The incretin hormones, glucose-dependent insulinotropic peptide and glucagon-like peptide-1, are secreted from intestinal K- and L cells, respectively, with the former being most abundant in the proximal small intestine, whereas the latter increase in number towards the distal gut. Although an overlap between K- and L cells can be observed immunohistochemically or in murine models expressing fluorescent markers under the control of the two hormone promoters, the majority (>80%) of labeled cells seems to produce only one of these hormones. Transcriptomic analysis showed a close relationship between small intestinal K- and L cells, and glucose sensing mechanisms appear similar in both cell types with a predominant role of electrogenic glucose uptake through sodium-coupled glucose transporter 1. Similarly, both cell types produce the long-chain fatty acid sensing G-protein-coupled receptors, FFAR1 (GPR40) and FFAR4 (GPR120), but differ in the expression/functionality of other lipid sensing receptors. GPR119 and FFAR2/3, for example, have clearly documented roles in glucagon-like peptide-1 secretion, whereas agonists for the endocannabinoid receptor type 1 have been found to show largely selective inhibition of glucose-dependent insulinotropic peptide secretion. In conclusion, although K- and L cell populations overlap and share key molecular nutrient-sensing mechanisms, subtle differences between the responsiveness of the different cell types might be exploited to differentially modulate glucose-dependent insulinotropic peptide or glucagon-like peptide-1 secretion.

Keywords: Gastric inhibitory polypeptide/glucose‐dependent insulinotropic peptide; Glucagon‐like peptide‐1; Secretion.

Publication types

  • Review

MeSH terms

  • Animals
  • Enteroendocrine Cells / metabolism*
  • Gastric Inhibitory Polypeptide / metabolism*
  • Glucagon-Like Peptide 1 / metabolism*
  • Glucose / metabolism*
  • Humans
  • Incretins / metabolism
  • Receptors, Cell Surface / metabolism
  • Receptors, G-Protein-Coupled / metabolism

Substances

  • FFAR1 protein, human
  • FFAR3 protein, human
  • FFAR4 protein, human
  • G-protein coupled receptor 43, human
  • GPR119 protein, human
  • Incretins
  • Receptors, Cell Surface
  • Receptors, G-Protein-Coupled
  • Gastric Inhibitory Polypeptide
  • Glucagon-Like Peptide 1
  • Glucose