Morin L, Giroix M H, Gangnerau M N, Bailbé D, Portha B
Laboratoire de Physiopathologie de la Nutrition, Université Paris, France.
Am J Physiol. 1997 May;272(5 Pt 1):E737-45. doi: 10.1152/ajpendo.1997.272.5.E737.
The effects of nutrient and neurotransmitter stimuli on insulin release, loss of phosphoinositides (PI), and production of inositol phosphates (InsP) were investigated in islets from neonatally streptozotocin-injected (nSTZ) rats. In islets from nSTZ rats, insulin secretory responses to 16.7 mM D-glucose and 10.0 mM D-glyceraldehyde were reduced compared with controls. Contents in phosphatidylinositol 4-monophosphate [PtdIns(4)P] and phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2], but not in phosphatidylinositol, were diminished. Glucose effects on breakdown of PtdIns(4)P and PtdIns(4,5)P2 and on total InsP accumulation were both reduced. D-Glucose was unable to increase the levels of both inositol trisphosphate isomers, Ins(1,3,4)P3 and Ins(1,4,5)P3. Glyceraldehyde also failed to promote InsP formation. By contrast, the ability of 1.0 mM carbachol or 300 nM cholecystokinin to stimulate insulin secretion and InsP generation was still observed. Thus a disturbed coupling between nutrient recognition and activation of phospholipase C, possibly together with a shortage of available polyphosphoinositides, could be responsible for the altered islet PI turnover in the nSTZ rats. It is proposed that such defects may contribute to the impairment of glucose-stimulated insulin secretion in this model of non-insulin-dependent diabetes mellitus.
研究了营养物质和神经递质刺激对新生期注射链脲佐菌素（nSTZ）大鼠胰岛胰岛素释放、磷酸肌醇（PI）丢失和肌醇磷酸（InsP）生成的影响。与对照组相比，nSTZ大鼠胰岛对16.7 mM D-葡萄糖和10.0 mM D-甘油醛的胰岛素分泌反应降低。磷脂酰肌醇4-单磷酸[PtdIns(4)P]和磷脂酰肌醇4,5-二磷酸[PtdIns(4,5)P2]的含量减少，但磷脂酰肌醇的含量未减少。葡萄糖对PtdIns(4)P和PtdIns(4,5)P2分解以及总InsP积累的影响均降低。D-葡萄糖无法增加两种肌醇三磷酸异构体Ins(1,3,4)P3和Ins(1,4,5)P3的水平。甘油醛也未能促进InsP的形成。相比之下，仍可观察到1.0 mM卡巴胆碱或300 nM胆囊收缩素刺激胰岛素分泌和InsP生成的能力。因此，营养物质识别与磷脂酶C激活之间的耦合紊乱，可能与可用多磷酸肌醇的短缺一起，可能是nSTZ大鼠胰岛PI周转改变的原因。有人提出，这种缺陷可能导致非胰岛素依赖型糖尿病模型中葡萄糖刺激的胰岛素分泌受损。
