| Project/Area Number |
12671117
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Metabolomics
|
|---|
| Research Institution | Kumamoto University |
|---|
Principal Investigator |
ARAKI Eiichi KUMAMOTO UNIVERSITY MEDICAL SHOOL, PROFESSOR, 医学部, 教授 (10253733)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
TOYONAGA Tetsushi KUMAMOTO UNIVERSITY MEDICAL SHOOL, RESEARCH ASSISTANT, 医学部, 助手 (60295128)
MIYAMURA Nobuhiro KUMAMOTO UNIVERSITY MEDICAL SHOOL, RESEARCH ASSISTANT, 医学部・附属病院, 助手 (40274716)
笹原 誉之 熊本大学, 医学部, 助手 (20304991)
|
|---|
| Project Period (FY) |
2000 – 2001
|
| Project Status |
Completed (Fiscal Year 2001)
|
| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2000: ¥2,100,000 (Direct Cost: ¥2,100,000)
|
|---|
| Keywords | insulin resistance / obesity / IRS-1 / diabetes mellitus |
|---|
| Research Abstract |
IRS-1 is one of the major substrates for insulin receptor. IRS-1 gene polymorphisms have been identified m type 2 diabetes patients in a heterozygous manner, and some mutant IRS-1 show impaired insulin signal in vitro. However, it is unclear how the IRS-1 polymorphisms contribute to the development of type 2 diabetes in human, since the heterozygous IRS-1 knockout (IRS-1 +/-) mice showed no abnormality. In this study, we created obese IRS-1 +/- mice by administration of gold-thioglucose (GTG) and studied the impact of reduced IRS-1 expression in obesity-linked insulin resistance. GTG administration in IRS-1 +/- mice as well as in wild type (WT) mice, acieved 〜30 % body weight gain from their saline-injected controls. Both obese IRS-1+/- and obese WT revealed elevated fasting insulin levels compared to their lean controls with no significant difference in fasting glucose. The insulin level in obese IRS-1+/- was 1.5-fold higher than that in obese WT (p<0.05). The blood glucose levels upon glucose load were significantly elevated in obese groups when compared with their lean controls, and which were significantly higher in obese IRS-1 +/- than in obese WT. In insulin tolerance test, obese IRS-1 +/- revealed profound insulin resistance compared to obese WT. The size in islets of obese IRS-1 +/- mice were about 1.4-fold larger than that in obese WT. Obese IRS-1 +/- showed a decrease in expression of insulin receptor in the liver and IRS-1 in the muscle compared from obese WT mice, which could in part explain profound insulin resistance in obese IRS-1 +/-. These results support the idea that IRS- 1 gene is the suspectable gene for type 2 diabetes and its polymorphisms in human could worsen insulin resistance in the presence of additional factors, such as obesity.
|
