2012 Fiscal Year Final Research Report
Study of protective effects and transcriptional regulation by a novel fatty acid receptor in pancreatic beta cells: its implication in lipotoxicity and glucose intolerance
| Project/Area Number |
23791029
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Metabolomics
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| Research Institution | Kyoto University |
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Principal Investigator |
TOMITA Tsutomu 京都大学, 医学研究科, 非常勤講師 (50402897)
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| Project Period (FY) |
2011 – 2012
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| Keywords | GPR40 / 脂肪毒性 / 糖尿病 / 耐糖能異常 / レプチン |
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| Research Abstract |
To explore the significance of GPR40 in leptin deficiency, GPR40 mRNA expression was assessed in pancreatic islets of genetically obese leptin-deficient rats (Lepmkyo/mkyo), which were established by our laboratory. Body weight of Lepmkyo/mkyowas increased an age-dependent manner. Hypertriglyceridimia and glucose intorelance were worsened in parralell with the progression of obesity. After the age of ~52 weeks, body weight of Lepmkyo/mkyowas decreased and they dead around the age of 60 weeks. Liver lipid concentration and blood transaminase were markedly increased in Lepmkyo/mkyo, suggesting involvement of liver failure in the death of Lepmkyo/mkyo. Fasting insulin levels were markedly increased in Lepmkyo/mkyo, and beta cell area was markedly increased. In contrast, early insulin response after glucose load was markedly decreased. GPR40 mRNA levels were decreased in pancreatic islets of Lepmkyo/mkyo, suggesting possible involvement of GPR40 in insulin secretion in leptin deficient obesity-associated glucose intolerance.
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