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Erschienen in:
30.03.2017 | Commentary
Role of GIP receptor signaling in β-cell survival
Erschienen in: Diabetology International | Ausgabe 2/2017
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Gastric inhibitory polypeptide/glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are two major incretin hormones secreted by enteroendocrine K cells and L cells into the circulation after meal ingestion. Nutrients such as glucose, fat, and protein induce incretin secretion. In β cells, GIP and GLP-1 bind to their respective class B G-protein-coupled receptor (GPCR), namely the GIP receptor (GIPR) and the GLP-1 receptor (GLP-1R), respectively, to potentiate glucose-dependent insulin secretion through cyclic adenosine 3′,5′-monophosphate (cAMP) protein kinase A (PKA) and exchange protein (directly activated by cAMP 2 (Epac2) signaling) (Fig. 1). Systemic incretin receptor-knockout and incretin peptide-knockout mice exhibit impaired glucose tolerance due to a lack of incretin-induced insulin secretion [1‐3]. Thus, the insulinotropic actions of GIP and GLP-1 play an important role in postprandial insulin secretion.
Fig. 1
Molecular mechanism of GIP- and GLP-1-induced insulin secretion and β-cell survival. GIP and GLP-1 potentiate glucose-dependent insulin secretion through PKA and Epac2 (black arrows). GLP-1 is well known to be associated with β-cell survival (as it exerts an antiapototic effect), reduction of ER stress, and β-cell maturation and differentiation (blue arrows). Campbell et al. have shown a new pathway for GIP-induced β-cell survival (red arrows)
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