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Updated: Jun 1, 2026

Mechanisms Underlying Gut Hormone Secretion Using the Isolated Perfused Rat Small Intestine
Published on: February 26, 2019
[Molecular mechanism of insulin secretion facilitated by incretin]
Yukihiro Fujita1, Masakazu Haneda
1Division of Metabolism and Biosystemic Science, Department of Internal Medicine, Asahikawa Medical University.
Abstract:
Incretins, such as GIP and GLP-1 enhance insulin secretion from pancreatic beta cells in a glucose dependent manner. Incretins potentiate adenylate cyclase activity trough their G-protein coupled receptors and then increase intracellular cAMP level. Intracellular cAMP modulates insulin secretion by both PKA-dependent and PKA-independent pathways. PKA potentiates intracellular Ca2+ influx via phosphorylation of voltage-dependent calcium channel(VDCC), which increases insulin exocytosis. PKA also phosphorylates K(ATP) channel and facilitates insulin release. In contrast, Epac2 potentiates insulin secretion by cAMP in a PKA-independent pathway. The small G-protein Rap1, which is activated specifically through Epac2, contributes the first phase of insulin secretion possibly by control of insulin granules fusion to plasma membrane.
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