HYPERRESPONSE IN CALCIUM-INDUCED INSULIN RELEASE FROM ELECTRICALLY PERMEABILIZED PANCREATIC-ISLETS OF DIABETIC GK RATS AND ITS DEFECTIVE AUGMENTATION BY GLUCOSE

被引：22

作者：

OKAMOTO, Y ^{[1
]}

ISHIDA, H ^{[1
]}

TSUURA, Y ^{[1
]}

YASUDA, K ^{[1
]}

KATO, S ^{[1
]}

MATSUBARA, H ^{[1
]}

NISHIMURA, M ^{[1
]}

MIZUNO, N ^{[1
]}

IKEDA, H ^{[1
]}

SEINO, Y ^{[1
]}

机构：

[1] TAKEDA CHEM IND LTD, PHARMACEUT RES LABS 2, OSAKA, JAPAN

来源：

DIABETOLOGIA | 1995年 / 38卷 / 07期

关键词：

INSULIN RELEASE; INTRACELLULAR CALCIUM; EXOCYTOSIS; GK RAT; PERMEABILIZED ISLETS;

D O I：

10.1007/s001250050351

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

In spontaneously diabetic GK rats, insulin secretion from pancreatic beta cells in response to glucose is selectively impaired, probably due to deficient intracellular metabolism of glucose and impaired closure of K-ATP channels during glucose stimulation. By using electrically permeabilized islets of GK rats, we explored the functional modulations in exocytotic steps distal to the rise in [Ca2+]i in the diabetic condition. At 30 nmol/l Ca2+ (basal conditions) insulin release was similar between GK and non-diabetic control Wistar rats. In response to 3.0 mu mol/l Ca2+ (maximum stimulatory conditions), insulin release was significantly augmented in permeabilized GK islets (p < 0.01). Raising glucose concentrations from 2.8 to 16.7 mmol/l further augmented insulin release induced by 3.0 mu mol/l Ca2+ from permeabilized control islets(p < 0.001), but had no effect on that from permeabilized GK islets. The stimulatory effect of glucose on insulin release from permeabilized control islets was partly inhibited by 2,4-dinitrophenol, an inhibitor of mitochondrial oxidative phosphorylation (p < 0.01), The hyperresponse to Ca2+ in GK islets may play a physiologically compensatory role on the putative functional impairment both in [Ca2+]i rise and energy state in response to glucose in diabetic beta cells, and may explain the relative preservation of insulin release induced by non-glucose depolarizing stimuli, such as arginine from pancreatic islets in non-insulin-dependent diabetes mellitus.

引用

页码：772 / 778

页数：7

共 45 条

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