| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Outline of Final Research Achievements |
Glucolipotoxicity, a combination of high glucose and elevated free fatty acids (FFA), induces β cell dysfunction and death. High glucose and FFA both activate novel protein kinase c (Pkc), including Pkcδ. However, the role of Pkcδ in diabetes remains unclear. Wild-type mice on neonate streptozotocin plus high-fat diet showed impaired glucose tolerance and reduced insulin secretion. Prkcd deficiency in β cells improved glucose tolerance and insulin secretion. Prkcd deficiency in β cells ameliorated β cell mass via reduced β cell death. To confirm the mechanisms of PKCδ in β cells, we used MIN6 cells. High glucose and palmitate activated PKCδ and induced MIN6 cell death. Palmitate reduced Pdx1 protein expression and phosphorylated Pdx1 at T11. PKCδ deficiency prevented palmitate-induced MIN6 cell death and inhibited Pdx1 protein reduction and phosphorylation. These results suggest that glucolipotoxicity induces β cell death via PKCδ-Pdx1 pathway.
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