Marie J C, Bailbé D, Gylfe E, Portha B
Laboratoire de Physiopathologie de la Nutrition, CNRS-ESA 7059, Université Paris VII/D. Diderot, 2 Place Jussieu, F-75251 Paris, France.
J Endocrinol. 2001 Apr;169(1):169-76. doi: 10.1677/joe.0.1690169.
We examined to what extent the abnormal glucose-dependent insulin secretion observed in NIDDM (non-insulin-dependent diabetes mellitus) is related to alterations in the handling of cytosolic Ca2+ of islets of Langerhans. Using two recognized rat models of NIDDM, the GK (Goto-Kakizaki) spontaneous model and the nSTZ (neonatal streptozotocin) induced model, we could detect several common alterations in the glucose-induced [Ca2+]i cytosolic responses. First, the initial reduction of [Ca2+]i following high glucose (16.7 mM) observed routinely in islets obtained from non-diabetic Wistar rats could not be detected in GK and nSTZ islets. Second, a delayed response for glucose to induce a subsequent 3% increase of [Ca2+]i over basal level was observed in both GK (321+/-40 s, n=11) and nSTZ (326+/-38 s, n=13) islets as compared with Wistar islets (198+/-20 s, n=11), values representing means+/-s.e.m. Third, the rate of increase in [Ca2+]i in response to a high glucose challenge was 25% and 40% lower in GK and nSTZ respectively, as compared with Wistar islets. Fourth, the maximal Ca2+ level reached after 10 min of perifusion with 16.7 mM glucose was lower with GK and nSTZ islets and represented respectively 60% and 90% of that of Wistar islets. Further, thapsigargin, a blocker of Ca2+/ATPases (SERCA), abolished the initial reduction in [Ca2+]i observed in response to high glucose and induced fast [Ca2+]i oscillations with high amplitude in Wistar islets. The latter effect was not seen in GK and nSTZ islets. In these two NIDDM models, several common alterations in glucose-induced Ca2+ handling were revealed which may contribute to their poor glucose-induced insulin secretion.
我们研究了在非胰岛素依赖型糖尿病（NIDDM）中观察到的异常葡萄糖依赖性胰岛素分泌与胰岛细胞溶质Ca2+处理改变的相关程度。使用两种公认的NIDDM大鼠模型，即GK（Goto-Kakizaki）自发模型和nSTZ（新生链脲佐菌素）诱导模型，我们能够检测到葡萄糖诱导的[Ca2+]i细胞溶质反应中的几种常见改变。首先，在从非糖尿病Wistar大鼠获得的胰岛中常规观察到的高葡萄糖（16.7 mM）后[Ca2+]i的初始降低在GK和nSTZ胰岛中未被检测到。其次，与Wistar胰岛（198+/-20 s，n = 11）相比，在GK（321+/-40 s，n = 11）和nSTZ（326+/-38 s，n = 13）胰岛中均观察到葡萄糖诱导的[Ca2+]i在基础水平上随后增加3%的延迟反应，数值表示平均值+/-标准误。第三，与Wistar胰岛相比，GK和nSTZ胰岛中对高葡萄糖刺激的[Ca2+]i增加速率分别低25%和40%。第四，用16.7 mM葡萄糖灌流10分钟后达到的最大Ca2+水平在GK和nSTZ胰岛中较低，分别为Wistar胰岛的60%和90%。此外，毒胡萝卜素，一种Ca2+/ATP酶（SERCA）阻滞剂，消除了对高葡萄糖反应中观察到的[Ca2+]i的初始降低，并在Wistar胰岛中诱导了高振幅的快速[Ca2+]i振荡。后一种效应在GK和nSTZ胰岛中未见到。在这两种NIDDM模型中，揭示了葡萄糖诱导的Ca2+处理中的几种常见改变，这可能导致它们较差的葡萄糖诱导胰岛素分泌。
