The role of GIP in α-cells and glucagon secretion.

Journal Article (Journal Article;Review)

Glucose-dependent insulinotropic polypeptide (GIP) is an intestinally derived peptide that is secreted in response to feeding. The GIP receptor (GIPR) is expressed in many cell types involved in the regulation of metabolism, including α- and β-cells. Glucagon and insulin exert tremendous control over glucose metabolism. Thus, GIP action in islets strongly dictates metabolic control in the postprandial state. Loss of GIPR activity in β-cells is a characteristic of type 2 diabetes (T2D) which associates with reduced postprandial insulin secretion and hyperglycemia. Less is known about GIPR activity in α-cells or the control of glucagon secretion. GIP stimulates glucagon secretion in a glucose-dependent manner in healthy people, with enhanced activity at lower glycemia. However, GIP stimulates glucagon secretion even at hyperglycemia in people with T2D, suggesting that inappropriate GIPR activity in α-cells contributes to the pathogenesis of T2D. Here, we review the literature describing GIP action and GIPR activity in the α-cell, detailing the basic science that has shaped the view of how GIP regulates glucagon secretion. We also contrast the effects of GIP on glucagon secretion in healthy and T2D people. Finally, we contextualize these observations in light of recent work that redefines the role of glucagon in glucose homeostasis, suggesting that hyperglucagonemia per se does not drive hyperglycemia. As new medications for T2D that incorporate GIPR activity are being developed, it is clear that a better understanding of GIPR activity beyond the β-cell is necessary. This work highlights the importance of focusing on the GIPR in α-cells.

Full Text

Duke Authors

Cited Authors

  • El, K; Campbell, JE

Published Date

  • March 2020

Published In

Volume / Issue

  • 125 /

Start / End Page

  • 170213 -

PubMed ID

  • 31785304

Pubmed Central ID

  • PMC7580028

Electronic International Standard Serial Number (EISSN)

  • 1873-5169

Digital Object Identifier (DOI)

  • 10.1016/j.peptides.2019.170213

Language

  • eng

Conference Location

  • United States