2007 Fiscal Year Final Research Report Summary
Search for novel mechanisms of insulin secretion by combination of proteom analysis and HPLC
| Project/Area Number |
17590956
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Endocrinology
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| Research Institution | Shinshu University |
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Principal Investigator |
KOMATSU Mitsuhisa Shinshu University, 大学院・医学系研究科, Associate Professor (90221978)
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| Co-Investigator(Kenkyū-buntansha) |
KABURAGI Yasushi International Medical Center of Japan, Department of Metabolic Disorder, Director (40342927)
NODA Mitsuhiko International Medical Center of Japan, Director (90237850)
AIZAWA Toru Shinshu University, 医学部, Professor (90150896)
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| Project Period (FY) |
2005 – 2007
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| Keywords | insulin release / secretion / acvlation / proteosome / type 2 diabetes / branched-chian amino acids |
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| Research Abstract |
Insulin release from pancreatic B-cell is regulated by multiple distinct mechanisms, which are mutually related. Among various insulin secretagogues, glucose is the most powerful and important one. Glucose is known to stimulate insulin release via KATP channel-dependent and -independent mechanisms. Molecular basis for the KATP channel-dependent mechanism has relatively well established. Our research purpose is, therefore, to elucidate the mechanisms of KATP channel-independent pathways. During this research project, we first identify two distinct proteins that are palmitoylated in the pancreatic B-cell by using two-dimensional gel electrophoresis. This was confirmed by proteom analysis; aminoacid sequence analysis revealed that they were cofilin and destrin. In pancreatic B-cell lines, cofilin and destrin were successfully knocked down by the respective siRNA. However, glucose-stimulated insulin release was not attenuated by these treatments. Thus, functional importance of the two proteins remained unknown. As a next step to approach the physiological importance of protein palmitoylation, we established a novel method to detect palmitoylated proteins specifically. By using this new technique, we are currently trying to identify newer player in the stimulus-secretion coupling in pancreatic B-cell. In another aspect of our achievement is that branch-amino acids significantly lower plasma glucose in diabetic animals. We also obtained preliminary results suggesting the branched-chain amino acid exhibit insulinotropic action via previously unknown mechanisms. In future, we will approach to mechanisms of impaired insulin secretion in patients with type 2 diabetes by extending our knowledge of the mechanisms of insulin secretion.
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