Morin L, Giroix M H, Portha B
Laboratoire de Physiopathologie de la Nutrition, URA CNRS 307, Université Paris, France.
Biochem Biophys Res Commun. 1996 Nov 12;228(2):573-8. doi: 10.1006/bbrc.1996.1700.
Phosphoinositide (PI) synthesis and hydrolysis were investigated in pancreatic islet homogenates from neonatal streptozotocin diabetic (n-STZ) and control rats. In the diabetics, ATP, in absence of Ca2+, failed to increase the amount of phosphatidylinositol 4-phosphate (PtdInsP) and phosphatidyl inositol 4, 5-bisphosphate (PtdInsP2) at variance with the pattern in controls. Also, the Ca(2+)-stimulated generation of inositol phosphates (InsP) was dramatically decreased, whether in the absence or presence of ATP. Moreover, phosphatidylinositol (PtdIns) kinase activity was reduced while PtdInsP kinase activity was not impaired. These data suggest that the suppressed formation of PtdInsP and subsequent PtdInsP2 synthesis, concomitantly with a decreased Ca(2+)-stimulated phospholipase C activity, may participate to the alteration of the PI pathway, the limitation of the InsP production, and finally the impairment of the insulin release in the n-STZ model of non-insulin-dependent diabetes.
研究了新生链脲佐菌素诱导的糖尿病（n-STZ）大鼠和对照大鼠胰岛匀浆中的磷酸肌醇（PI）合成与水解。在糖尿病大鼠中，在无Ca2+的情况下，ATP未能增加磷脂酰肌醇4-磷酸（PtdInsP）和磷脂酰肌醇4,5-二磷酸（PtdInsP2）的量，这与对照组的模式不同。此外，无论有无ATP，Ca(2+)刺激的肌醇磷酸（InsP）生成均显著降低。此外，磷脂酰肌醇（PtdIns）激酶活性降低，而PtdInsP激酶活性未受损。这些数据表明，PtdInsP生成受抑制以及随后的PtdInsP2合成减少，同时Ca(2+)刺激的磷脂酶C活性降低，可能参与了PI途径的改变、InsP产生的限制，最终导致非胰岛素依赖型糖尿病n-STZ模型中胰岛素释放受损。
