2002 Fiscal Year Final Research Report Summary
Pathophysiological Analysis of Leptin Resistance in Type 2 Diabetes Mellitus
| Project/Area Number |
13671205
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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 |
Metabolomics
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| Research Institution | Kawasaki Medical School |
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Principal Investigator |
MATSUDA Masafumi Kawasaki Medical School, Department of Medicine, Lecturer, 医学部, 講師 (00199811)
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| Project Period (FY) |
2001 – 2002
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| Keywords | leptin / type 2 diabetes mellitus / rat / glucose metabolism / adipocytokines |
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| Research Abstract |
We administered leptin on rats to figure out the importance of leptin resistance for the development of type 2 diabetes mellitus. Three hours after the leptin administration, we started 3-^3 H- glucose infusion, and performed hyperinsulinemic euglycemic clamp. Rd and Ra were calculated by Steele's equation. Male Wistar rats at the age of 6 weeks had the basal Ra of 5.6^^+__- 0.4 mg/kg per min and Rd of 5.7 ^^+__- 0.5 mg/kg per min under infusion of 3 microg/ kg per min, Rd was 18.5 ^^+__- 0.8 mg/kg per min. addition of leptin (10 microg/kg per min), Rd was increased to 20.8 ^^+__- 0.6 mg/kg per min. high fat diet to rats revealed reduced Rd of 15.2 ^^+__- 0.4 mg/kg per min with 10 Mu/kg per min insulin infusion, and this was increased to 18.3 ^^+__- 0.4 mg/kg per min with leptin infusion. Zucker fatty rat (fa/ fa) had reduced rate of glucose disposal of 8.6 ^^+__- 0.8 mg/kg per min, and failed to respond to leptin administration. Insulin resistance exists under the severe leptin resistance
Adipocytokines (leptin, TNF- alpha, resistin, and adiponectin) produced from adipose tissue and the characteristic features of type 2 diabetes mellitus were also addressed to identify the role of adipcytokines in Japanese type 2 diabetic subjects who is not insulin resistant. Despite the lesser extent of insulin resistance in this population, adipocytokines had an impact on vascular damabes. The role of adipocytokines including leptin on the type 2 diabetes mellitus has to be further clarified
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