| 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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| 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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