Intracellular calcium signaling of pancreatic B cell and its deterioration in diabetes mellitus.
| Project/Area Number |
09671042
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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 |
内分泌・代謝学
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| Research Institution | Kagawa Medical University (1998)
Hamamatsu University School of Medicine (1997) |
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Principal Investigator |
TAMINATO Tomohiko Kanagawa Medical University, Dept.of Laboratory Medicine, Professor, 医学部, 教授 (90107954)
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| Co-Investigator(Kenkyū-buntansha) |
OKI Yutaka Hamamatsu University School of Medicine, The second Dept.of Medicine, Research A, 医学部, 助手 (20169204)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1998: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1997: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | Insulin secretion / Diabetes mellitus / CD38 / ADP-ribosyl cyclase / Cyclic ADP-ribose / CD38 antibody / D-glucose / Intracellular calcium ([Ca2+]i) |
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| Research Abstract |
The present study was aimed to clarify the role of CD38 antigen (ADP-ribosyl cyclase) in insulin secretion and its early deterioration of in diabetes mellitus. CD38 antigen catalyzes NAD to produce cyclic ADP-ribose, a novel intracellular calcium-mobilizing substance. We carried out the experiments using anti-CD38 antibody to find the role of CD38 on insulin release from Min 6 cells, a clonal pancreatic B cells. Pretreatment of anti CD38 antibody caused dose-related inhibition of D-glucose-induced insulin release from Min 6 cells. The antibody also inhibited insulin release elicited by D-mannose, L-arginine, a-KIC, carbamylcholine, glucagon, forskolin, and dibutyryl cyclic AMP.The rise of [Ca2+]i in response to glucose or carbamylcholine was significantly inhibited by the pretreatment of anti-CD38 antibody, whereas [Ca2+]i in response to glibenclamide was augmented. In NOD mice, a n animal model of insulin-dependent diabetes mellitus, anti-CD38 antibody was detected with high prevalence.
These results clearly indicate a crucial significance of CD38-cyclic ADP-ribose system in signal transduction in insulin secretion, and moreover, an autoantibody, as shown in NOD mice, may play an important role in the pathogenesis of diabetes.
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Report
(3 results)
Research Products
(11 results)
