Modeling analysis on the molecular mechanisms underlying insulinotropic effects of incretin hormone in pancreatic beta cells.

2014 Fiscal Year Final Research Report

• Project/Area Number: 24790211
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General physiology
• Research Institution: Ritsumeikan University
• Principal Investigator: TAKEDA Yukari 立命館大学, 生命科学部, 助教 (20582159)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 受容体・細胞内シグナル伝達

Outline of Final Research Achievements

Upon elevation of plasma glucose concentration, pancreatic β-cells generate bursts of action potentials to induce cyclic changes in [Ca2+]i and regulate pulsatile insulin release. This glucose-dependent insulin secretion is synergistically enhanced by an incretin hormone, GLP-1. To date, it has been well established that GLP-1 increases [cAMP] and subsequently activates PKA and Epac, modulating the activities of ion channels at the plasma membrane and ER, which in turn modify the pattern of burst as well as Ca2+ mobilization events. However, because of complex interactions between multiple cellular factors and ion channels or transporters involved in the GLP-1 effects, quantitative aspects of the molecular mechanisms have not yet been determined. In order to overcome this difficulty, we adopted a strategy of modeling analysis; simulation study and mathematical analysis, and quantitatively investigated the mechanisms underlying the GLP-1 effects on cellular functions.

Free Research Field

医歯薬学