Budget Amount *help |
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2013: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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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.
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