Alcázar O, Qiu-yue Z, Giné E, Tamarit-Rodriguez J
Department of Biochemistry, Complutense University Medical School, Madrid, Spain.
Diabetes. 1997 Jul;46(7):1153-8. doi: 10.2337/diab.46.7.1153.
The secretory, metabolic, and signaling aspects of glucose/palmitate interaction on beta-cell function have been studied on rat islets. Palmitate potentiated the glucose-induced insulin response of perifused islets at suprathreshold (>3 mmol/l) sugar concentrations. This potentiating effect could be suppressed by 8-bromo-cGMP, which also blocks palmitate metabolism. Palmitate did not modify glucose utilization, but it slightly reduced glucose oxidation and concomitantly increased lactate production. The very low rate of palmitate oxidation (80-fold lower than that of 20 mmol/l glucose) might explain its lack of effect on glycolysis and hence that the glucose/fatty acid cycle is inoperative in islet cells. However, glucose determines the metabolic fate of exogenous palmitate, which is mainly diverted toward lipid synthesis at high sugar concentrations and might then generate lipid messengers for cell signaling. Palmitate did not increase glucose-induced production of inositol-1,4,5-trisphosphate, but it stimulated the translocation of protein kinase C activity from a cytosolic to a particulate fraction at 20 but not at 3 mmol/l glucose. This increased translocation was partially or completely blocked by hydroxycitrate or 8-bromo-cGMP, respectively, which are agents interfering with palmitate metabolism (inhibiting lipid synthesis). The metabolic interaction between glucose and palmitate might generate lipid messengers (diacylglycerol, phosphatidylserine) necessary for the activation of islet protein kinase C, which would in turn result in a potentiation of glucose-induced insulin secretion.
关于葡萄糖/棕榈酸酯相互作用对β细胞功能的分泌、代谢及信号转导方面的研究已在大鼠胰岛上展开。在高于阈值（>3 mmol/l）的糖浓度下，棕榈酸酯增强了经灌注胰岛对葡萄糖诱导的胰岛素反应。这种增强作用可被8-溴-cGMP抑制，8-溴-cGMP也可阻断棕榈酸酯的代谢。棕榈酸酯未改变葡萄糖的利用，但略微降低了葡萄糖氧化并同时增加了乳酸生成。棕榈酸酯的氧化速率极低（比20 mmol/l葡萄糖的氧化速率低80倍），这可能解释了其对糖酵解缺乏影响，因而葡萄糖/脂肪酸循环在胰岛细胞中不起作用。然而，葡萄糖决定了外源性棕榈酸酯的代谢命运，在高糖浓度下，棕榈酸酯主要转向脂质合成，然后可能生成用于细胞信号转导的脂质信使。棕榈酸酯未增加葡萄糖诱导的肌醇-1,4,5-三磷酸的生成，但在20 mmol/l葡萄糖而非3 mmol/l葡萄糖条件下，它刺激了蛋白激酶C活性从胞质向颗粒部分的转位。这种增加的转位分别被羟基柠檬酸或8-溴-cGMP部分或完全阻断，这两种物质是干扰棕榈酸酯代谢（抑制脂质合成）的试剂。葡萄糖与棕榈酸酯之间的代谢相互作用可能产生激活胰岛蛋白激酶C所需的脂质信使（二酰基甘油、磷脂酰丝氨酸），这反过来会增强葡萄糖诱导的胰岛素分泌。
