Project/Area Number |
61570538
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Research Category |
Grant-in-Aid for General Scientific Research (C)
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Allocation Type | Single-year Grants |
Research Field |
内分泌・代謝学
|
Research Institution | Chiba University School of Medicine |
Principal Investigator |
MAKINO Hideichi Second Department of Internal Medicine, 医学部第二内科, 講師 (50009578)
|
Project Period (FY) |
1986 – 1987
|
Project Status |
Completed (Fiscal Year 1987)
|
Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1987: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1986: ¥1,400,000 (Direct Cost: ¥1,400,000)
|
Keywords | Insulin / Fat cells / Phosphodiesterase / Griseolic acid / 食餌制限 / ソマトメジンC / griseolic acid / cAMP / 脂肪分解抑制作用 / phosphodiesterase / Griseolic Acid |
Research Abstract |
In order to clarify the mechanism of antilipolytic action of insulin, the role of insulin-sensitive PDE was incestigated, using a new phosphodiesterase (PDE) inhibitor, Griseolic acid. Griseolic acid (GA) inhibited PDE, resulting in cAMP production and lipolysis. GA also depressed activation of PDE by insulin dosedependently, resulting in decreased antilypolysis and cAMP reduction by insulin. These results indicate an essential role of PDE on antilipolytic action of insulin. On the other hand PDE activation system has been changed in various pathophysiological states. Former study revealed impaired insulin action in fat cells of spontaneous obese rat and KK mouse. In this study it was observed that diet restriction restored insulin sensitivity to PDE in obese rat fat cells. On the contrary high fat diet induced insulin resistance in PDE system of fat cells. These results indicate insulin resistance is reversible in PDE activation system of obese rat fat cells. It is well known that first step of insulin action is the binding to the receptor. In PDE system it was demonstrated that such was true, using trypsin treatment and antiinsulin receptor antibody. Somatomedin C is known to have an insulin-like action. It was shown that it activated PDE in a similar manner to insulin. These results indicate PDE activation system is a very useful method to investigate insulin action.
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