Role of GIP receptor signaling in β-cell survival

Excerpt

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.

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