Impair ment of glucose-responsiveintracellular signaling of pancreatic B cell in diabetes mellitus.

糖尿病中胰腺 B 细胞葡萄糖反应性细胞内信号传导受损。

• 批准号: 06671017
• 负责人: TAMINATO Tomohiko
• 金额: $ 1.28万
• 依托单位: Hamamatsu University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06671017/
• 关键词: Insulin secretion; Diabetes mellitus; CD38; ADP-ribosyl cyclase; NAD; Cyclic ADP-ribose; Intracellular calcium ([Ca^<2+>]i); D-glucose; グルコース; 細胞内カルシウム; 膵B細胞; カルシウム シグナリング; アロキサン

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.

本研究的目的是阐明CD38抗原（ADP-核糖基环化酶）在胰岛素分泌和糖尿病早期恶化中的作用。 CD38抗原催化ZES NAD可产生环状ADP-核糖，Enovel细胞内钙润滑物质。我们使用抗CD38抗体进行了实验，以发现CD38在Min 6细胞中胰岛素释放的作用，即克隆胰腺B细胞。抗CD38抗体的预处理导致对D-葡萄糖诱导的剂量相关的抑制D-葡萄糖诱导的胰岛素从Min 6细胞中释放。该抗体还抑制了D-甘露糖，L-精氨酸，α-KIC，氨基甲酰胆碱，胰高血糖素，Forskolin和dibutyryl循环AMP引起的胰岛素释放。 [Ca^<2+>] I对Glibenclamide的响应进行了增强。这些结果清楚地证明了该抗体对葡萄糖诱导的Min 6细胞胰岛素的直接抑制作用，表明CD38-循环ADP-ribose系统在胰岛素分泌中信号传递中的至关重要。

项目成果

Taminato t.: "Inhibition of insulin release and intracellular Ca^<2+> response by anti-CD38 antibody." Biochem Biopys Res Commun.(in press). (1996)

Taminato t.：“抗CD38抗体抑制胰岛素释放和细胞内Ca^2反应。”

Taminato T.: "CD38 (ADP-ribosyl cyclase) is an important signal transdduction system in insulin secretion. (in Japanese)" Peptide Hormones in Pancreas. 15. 67-72 (1996)

Taminato T.：“CD38（ADP-核糖基环化酶）是胰岛素分泌中重要的信号转导系统。（日语）”胰腺中的肽激素。

Taminato T.: "Cyclic ADP-ribose and insulin secretion (in Japanese)" in "Recent progress in molecular diabetology-From basic science to clinical practice". 24-31 (1996)

Taminato T.：“分子糖尿病学的最新进展-从基础科学到临床实践”中的“循环ADP-核糖和胰岛素分泌（日语）”。

Taminato T.: "Inhibition of insulin rerease and intracellular Ca^<2+> response by anti-CD38 antibody." Biochem Biopys Res Commun.(発表予定). (1996)

Taminato T.：“抗CD38抗体对胰岛素释放和细胞内Ca 2+ 反应的抑制”（Biochem Biopys Res Commun）（待发表）。

田港朝彦: "CD38抗原(ADP-ribosyl cyclase)はインスリン分泌の重要な情報伝達システムである" Peptide Hormones in Pancreas. 15. 65-69 (1995)

Asahiko Taginato：“CD38 抗原（ADP-核糖基环化酶）是胰岛素分泌的重要信号转导系统”Peptide Hormones in Pancreas 15. 65-69 (1995)。