1995 Fiscal Year Final Research Report Summary
Impair ment of glucose-responsiveintracellular signaling of pancreatic B cell in diabetes mellitus.
| Project/Area Number |
06671017
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
内分泌・代謝学
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| Research Institution | Hamamatsu University School of Medicine |
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Principal Investigator |
TAMINATO Tomohiko Hamamatsu University School of Medicine, The second Dept. of Medicine, Lecturer, 医学部附属病院, 講師 (90107954)
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| Project Period (FY) |
1994 – 1995
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| Keywords | Insulin secretion / Diabetes mellitus / CD38 / ADP-ribosyl cyclase / NAD / Cyclic ADP-ribose / Intracellular calcium ([Ca^<2+>]i) / D-glucose |
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| Research Abstract |
The present study was aimed to clarify the role of CD38 antigen (ADP-ribosyl cyclase) in insulin secretion andits early deterioration of in diabetes mellitus. CD38 antigen cataly zes NAD to produce cyclic ADP-ribose, anovel 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, alpha-KIC,carbamylcholine, glucagon, forskolin, and dibutyryl cyclic AMP.The rise of [Ca^<2+>]i in response to glucose or carbamylcholine was significantly inhibited by the pretreatment of anti-CD38 antibody, whereas [Ca^<2+>]i in response to glibenclamide was augmented.
These results clearly demonstrate the direct inhibitory action of the antibody on glucose-induced insulin from Min 6 cells, indicating a crucial role of CD38-cyclic ADP-ribose system in signal transduction in insulin secretion.
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