1999 Fiscal Year Final Research Report Summary
Importance of obese gene product, leptin in physiological significance and application of therapeutics
| Project/Area Number |
10557241
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
TOKUMITSU Yukiko Grad. School of Pharm. Sci., Hokkaido Univ., Pro., 大学院・薬学研究科, 教授 (60001046)
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| Co-Investigator(Kenkyū-buntansha) |
HAZEKI Osamu Fac. Of Med., Hiroshima Univ., Pro., 医学部, 教授 (80142751)
MURAKAMI Takeshi Grad. School of Med., Hokkaido Univ., Inst., 大学院・医学研究科, 講師 (50271656)
MATSUOKA Ichiro Grad. School of Pharm. Sci., Hokkaido Univ., Asso. Pro., 大学院・薬学研究科, 助教授 (40157269)
OKAJIMA Fumikazu Inst. Of Metab. Res., Gunma Univ., Pro., 生体調節研究所, 教授 (30142748)
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| Project Period (FY) |
1998 – 1999
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| Keywords | Obese gene / Leptin / Rat adipocytes / 3T3-L1 adipocytes / Human obesity |
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| Research Abstract |
We studied the regulation of plasma leptin concentration and the appearance of insulin resistance in obesity. The results were described below.
(1) Wistar fatty rats used as a good model of NIDDM were increased the plasma levels of insulin, glucose, lipids, and obese gene product leptin. Especially, the levels of leptin and insulin were markedly increased at the early stage of obesity accompanied with the exclusive expression of ob gene mRNA in the adipocytes of fatty rats. Secretory patterns of leptin showed circadian rhythms, lowest secretion during daytime and highest elevation in midnight in lean rats, but did not show it in fatty rats. Plasma TNF-α concentration was also correlated with obesity and insulin resistance indicating the contribution to the development of NIDDM.
(2) Human obese subjects were increased plasma levels of insulin, leptin, lipids and TNF-α showing the being accompanied by insulin resistance. Insulin resistance is associated with increase in insulin secretion to preserve normo-glysemia. On the other hand, leptin concentration was correlated closely with percentage body fat in human obesity. Fortunately, it was shown that control of food intake and exercise improve these abnormal conditions and decrease the body weight.
(3) 3T3-L1 adipocytes differentiated by insulin/dexamethasone/IMBX secreted leptin. TNF-α prevented differentiation to adipocytes by inhibition of insulin action. Thiazolidinedione derivatives leading to the improvement of insulin sensitivity in human prevented the TNF-α action. These facts indicated that TNF-α induces insulin resistance and develops NIDDM and thiazolidinedione derivatives prevent the appearance of NIDDM.
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