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Is a Growth Factor for � (INS-1) Cells by Pleiotropic Signaling

By Glucose-dependent Insulinotropic Polypeptide, Andrea Trümper, Katja Trümper, Heidi Trusheim, Rudolf Arnold, Burkhard Göke and Dieter Hörsch


Activation of the G-protein-coupled receptor for glucose-dependent insulinotropic polypeptide facilitates insulin-release from pancreatic �-cells. In the present study, we examined whether glucosedependent insulinotropic polypeptide also acts as a growth factor for the �-cell line INS-1. Here, we show that glucose-dependent insulinotropic polypeptide induced cellular proliferation synergistically with glucose between 2.5 mM and 15 mM by pleiotropic activation of signaling pathways. Glucose-dependent insulinotropic polypeptide stimulated the signaling modules of PKA/cAMP regulatory element binder, MAPK, and PI3K/protein kinase B in a glucose- and dose-dependent manner. Janus kinase 2 and signal transducer and activators of transcription 5/6 pathways were not stimulated by glucose-dependent insulinotropic THE GLUCO-INCRETIN EFFECT results in higher insulin response and consecutive smaller increase in blood sugar after an oral glucose load compared with intravenous administration. Two major insulinotropic incretin hormones have been characterized: glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) (1, 2). GLP-1 is synthesized in entero-endocrine L-cells of the ileum and colon and released into circulation as bioactive truncated GLP-1 (7–36 amide). GLP-1 receptors are expressed on pancreatic �-cells, and activation of GLP-1 receptors at high glucose levels results in potentiation of glucose-dependent insulin secretion and activation of insulin gene transcription (1, 2). The incretin effect of GLP-1 is preserved in type II diabetes mellitus, which is currently exploited in clinical studies for the therapy of type II diabetes mellitus (2). In addition to its insulinotropic characteristics, GLP-1 also functions as a growth and differentiatio

Topics: kinas
Year: 2013
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