Studies on physiological function of GAD and GABA in pancreatic islet

胰岛GAD和GABA生理功能研究

• 批准号: 06671032
• 负责人: TANIGUCHI Hiroshi
• 金额: $ 1.22万
• 依托单位: Kobe University
• 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-06671032/
• 关键词: GAD; GABA; Pancreatic islet; Physiological function; 自己抗体

The physiological function of gamma-aminobutyric acid (GABA) decarboxylase (GAD) and its synthesizing GABA in pancreatic islets is studied by comparing the GABA level of islets with that of central nervous tissues in terms of responsiveness to drugs affecting GAD and GABA transaminase (GABA-T) , a metabolizing enzyme of GABA,and by observing the effect of some insulin release stimulators on GAD level in islets.(1) Studies in vivo(a) The intraperitoneal administration of 3-mercaptopropionic acid known to suppress GAD in central nervous tissues into Wistar rats decreased the GABA content in the hypocampus, hypothalamus, superior colliculus and striatum as well as in islets.(b) The similar injection of sodium valproate known to suppress GABA-T in central nervous tissues raised the GABA content in all abovementioned tissues.(2) Studies in vitro(a) Incubation of isolated Wistar rat islets with 3-mercaptopropionic acid or sodium valproate decreased or increased the GABA content in the islets respectively.(b) GAD level measured with Western blot in islets did not change by arginine which does not stimulate insulin synthesis but increased by glucose which stimulates insulin synthesis.These observations indicate that GAD as well as GABA-T are apparently similar in terms of pharmacological response between the central nervous tissues and the islets, and that the GAD in islets seems to play a role in insulin synthesis.

通过比较胰岛与中枢神经组织对影响GABA的药物和GABA代谢酶GABA转氨酶（GABA- t）的反应性，以及观察一些胰岛素释放刺激剂对胰岛GAD水平的影响，研究了γ -氨基丁酸（GABA）脱羧酶（GAD）及其合成GABA的生理功能。(1)体内研究(a) Wistar大鼠腹腔注射已知可抑制中枢神经组织GAD的3-巯基丙酸可降低其下丘脑、上丘、纹状体及胰岛GABA含量。(b)同样注射已知抑制中枢神经组织GABA- t的丙戊酸钠，上述各组织中GABA含量均升高。(2)体外研究(a) 3-巯基丙酸或丙戊酸钠对Wistar大鼠离体胰岛的培养分别降低或增加了胰岛中GABA的含量。(b)免疫印迹法测定的胰岛GAD水平未被不刺激胰岛素合成的精氨酸改变，而被刺激胰岛素合成的葡萄糖升高。这些观察结果表明，GAD和GABA-T在中枢神经组织和胰岛之间的药理反应明显相似，并且胰岛中的GAD似乎在胰岛素合成中发挥作用。

项目成果

Junichi Katoh et al.: "The effects of a convulsant, 3-mercaptopropionic acid, on the GABA level in rat pancreatic islets and brain, In-vivo and in-vitro" Pharmaceutical Sciences. 1. 23-25 (1995)

Junichi Katoh 等人：“惊厥药 3-巯基丙酸对大鼠胰岛和大脑中 GABA 水平的体内和体外影响”药物科学。

Hiroshi Taniguchi et al.: Physiological aspects of GAD-GABA system in the pancreatic islet. GABA : Receptos, Transporters and Metabolism (C.Tanaka and N.G.Bowery, editors) , Birkhauser Verlag, Basel, 7-12 (1996)

Hiroshi Taniguchi 等人：胰岛中 GAD-GABA 系统的生理学方面。

J. Katoh et al.: "Similarity of glutamalc decarboxylase and GABA transaminase in terms of response to their inhibitors in parcreatic islets in vitro" Acta Therapeutica. 20. 101-107 (1994)

J. Katoh 等人：“谷氨酸脱羧酶和 GABA 转氨酶在胰岛体外对其抑制剂的反应方面的相似性”Acta Therapeutica。

J. Katoh et al.: "A convulsant, 3-mercaptopropionic acid, decreases the level of GABA and GAD in rat parcreatic islets and brain" Experientia. 51. 217-219 (1995)

J. Katoh 等人：“3-巯基丙酸是一种惊厥剂，可降低大鼠胰岛和大脑中 GABA 和 GAD 的水平”Experientia。

J. Katoh et al.: "Diahetes Mellitus in Western Pacific Region" Korea Medical Publishing Co., 280 (1994)

J. Katoh 等：“西太平洋地区的糖尿病”，韩国医学出版社，280（1994）