Physiological and Pathophysiological Role of Glucagon-Like Peptide-I in the Regulation of Nutrient Homeostasis After the Meal.
Project/Area Number |
01570624
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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
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Research Institution | Institute of Clinical Medicine, University of Tsukuba |
Principal Investigator |
KAWAI Koichi Assistant professor of Medicine, 臨床医学系, 講師 (10111379)
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Project Period (FY) |
1989 – 1990
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Project Status |
Completed (Fiscal Year 1990)
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Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1990: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1989: ¥1,400,000 (Direct Cost: ¥1,400,000)
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Keywords | GLP-1 / Insulin / GIP / Pancreas perfusion / Incretin / Antagonist / Glucagon / GLP-1 / 糖尿病 / 血糖調節 / 構造活性相関 |
Research Abstract |
Following studied were performed by this grant. 1. Biological activities of GLP-1 in vivo : Bolus injection of pharmacological doses of GLP-1 (7-36) amide into unanesthetized normal dogs caused a transient increase in plasma insulin level, which brought on hypoglycemia without reactive increase in plasma glucagon. The degree of increase in the plasma glucose level induced by iv glucose infusion was reduced by coinfusion of GLP-1, which caused a high plasma insulin level comparing with a control experiment (coinfusion of vehicle of GLP-1). These results demonstrate the role of GLP-1 as an incretin (ref. 4). 2. Incretin effect in non-insulin dependent diabetes mellitus (NIDDM) : Using a perfused pancreas from a streptozocin NIDDM model rat, a characteristics of incretin effect (glucose dependent stimulation of insulin release) was examined with GLP-1 and GIP. The results demonstrated that incretin effect of these peptides was reduced in NIDDM and this abnormality was not normalized by the conventional insulin treatment. These abnormalities might be one of the causes of NIDDM (ref. 3). 3. Interaction of GLP-1 and other incretins : Physiologic doses of GLP-1 and GIP synergistically stimulated the insulin release from the isolated perfused rat pancreas and GLP-1 and CCK-8 additively stimulated it, which suggests the reason why physiologic doses of GLP-1 and GIP cause a potent stimulation of insulin release comparing with the effect of each peptide by itself (ref. 6). 4. Structure-activity study of GLP-1 : Comparing the insulinotropic effect of glucagon-family peptides and several analogues of GLP-1 synthesized by ourselves, we demonstrated that amino acids at position 7, 10, 15 and 17 in the amino acid sequence of GLP-1 are essential for its insulinotropic activity. Based on these results, two tentative antagonists of GLP-1 were synthesized and examined their activity in competing against the GLP-1's insulinotropic activity (ref. 1 and 5).
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Report
(3 results)
Research Products
(23 results)