Okamoto Y, Ishida H, Tsuura Y, Yasuda K, Kato S, Matsubara H, Nishimura M, Mizuno N, Ikeda H, Seino Y
Department of Metabolism and Clinical Nutrition, Kyoto University Faculty of Medicine, Japan.
Diabetologia. 1995 Jul;38(7):772-8. doi: 10.1007/s001250050351.
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 KATP 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 mumol/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 mumol/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.
在自发性糖尿病GK大鼠中，胰腺β细胞对葡萄糖作出反应时的胰岛素分泌选择性受损，这可能是由于葡萄糖的细胞内代谢不足以及葡萄糖刺激期间KATP通道关闭受损所致。通过使用电透化的GK大鼠胰岛，我们探究了糖尿病状态下细胞内钙离子浓度升高后胞吐步骤中的功能调节。在30 nmol/l钙离子浓度（基础条件）下，GK大鼠和非糖尿病对照Wistar大鼠的胰岛素释放相似。在3.0 μmol/l钙离子浓度（最大刺激条件）下，透化的GK胰岛中的胰岛素释放显著增加（p < 0.01）。将葡萄糖浓度从2.8 mmol/l提高到16.7 mmol/l可进一步增加透化的对照胰岛中由3.0 μmol/l钙离子诱导的胰岛素释放（p < 0.001），但对透化的GK胰岛中的胰岛素释放没有影响。葡萄糖对透化的对照胰岛胰岛素释放的刺激作用部分被线粒体氧化磷酸化抑制剂2,4-二硝基苯酚抑制（p < 0.01）。GK胰岛对钙离子的高反应性可能在糖尿病β细胞中对葡萄糖作出反应时细胞内钙离子浓度升高和能量状态的假定功能损害方面发挥生理补偿作用，并且可能解释了非胰岛素依赖型糖尿病患者胰岛中由非葡萄糖去极化刺激（如精氨酸）诱导的胰岛素释放的相对保留。
