Björk E, Kämpe O, Andersson A, Karlsson F A
Department of Internal Medicine, University Hospital, Uppsala, Sweden.
Diabetologia. 1992 May;35(5):490-3. doi: 10.1007/BF02342450.
This study examined the relationship between insulin secretion and expression of the 64 kDa/glutamic acid decarboxylase autoantigen in pancreatic islets. Islets isolated from Wistar rats were cultured for 3 days under different conditions: in 5.5 mmol/l glucose with or without alpha-ketoisocaproic acid or glipizide and in 28 mmol/l glucose with or without diazoxide. The 64 kDa/glutamic acid decarboxylase autoantigen was precipitated from lysates of [35S]-methionine-labelled islets with sera from patients with Type 1 (insulin-dependent) diabetes mellitus and identified by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and fluorography. In parallel, insulin contents of the islets and the media were determined as well as the rates of glucose-stimulated (pro)insulin biosynthesis. alpha-Ketoisocaproic acid and glipizide were found to stimulate the expression of the 64 kDa/glutamic acid decarboxylase autoantigen and also the rate of insulin secretion. Diazoxide on the other hand reduced the rate of the 64 kDa/glutamic acid decarboxylase autoantigen synthesis in parallel with an inhibition of glucose-stimulated insulin release. Under most of the conditions employed, (pro)insulin biosynthesis was not affected. The correlation found between the rate of insulin release and expression of the 64 kDa/glutamic acid decarboxylase autoantigen might provide an explanation for the earlier observed relationship between the functional demands on the Beta cells and their rate of destruction which may result in diabetes.
本研究检测了胰岛中胰岛素分泌与64 kDa/谷氨酸脱羧酶自身抗原表达之间的关系。从Wistar大鼠分离出的胰岛在不同条件下培养3天：分别培养于含或不含α-酮异己酸或格列吡嗪的5.5 mmol/l葡萄糖中，以及含或不含二氮嗪的28 mmol/l葡萄糖中。用1型（胰岛素依赖型）糖尿病患者的血清从[35S]-甲硫氨酸标记的胰岛裂解物中沉淀出64 kDa/谷氨酸脱羧酶自身抗原，并通过十二烷基硫酸钠-聚丙烯酰胺凝胶电泳和荧光自显影进行鉴定。同时，测定胰岛和培养基中的胰岛素含量以及葡萄糖刺激的（前）胰岛素生物合成速率。发现α-酮异己酸和格列吡嗪可刺激64 kDa/谷氨酸脱羧酶自身抗原的表达以及胰岛素分泌速率。另一方面，二氮嗪降低了64 kDa/谷氨酸脱羧酶自身抗原的合成速率，同时抑制了葡萄糖刺激的胰岛素释放。在大多数所用条件下，（前）胰岛素生物合成未受影响。胰岛素释放速率与64 kDa/谷氨酸脱羧酶自身抗原表达之间的相关性可能为早期观察到的β细胞功能需求与其破坏速率之间的关系提供解释，而这种关系可能导致糖尿病。
