Murthy V K, Shipp J C
J Clin Invest. 1981 Apr;67(4):923-30. doi: 10.1172/jci110141.
The syntheses of triglyceride and its precursors were increased when liver homogenates of ketotic diabetic rats were incubated with [U-14C]-glycero 3-phosphate and cofactors. Triolein sonicates produced a concentration-dependent inhibition of the synthesis of both diglyceride and triglyceride, whereas monoolein sonicates had no effect. Rat serum very low density lipoproteins, like triolein sonicates, inhibited the synthesis of diglyceride and triglyceride. Furthermore, the intracellular form of very low density lipoproteins, namely nascent very low density lipoproteins, also inhibited the synthesis of diglyceride and triglyceride. A higher apparent I50 (concentration of inhibitor that produces 50% inhibition of activity) was observed in liver homogenates of ketotic diabetic rats for inhibition of triglyceride or diglyceride synthesis by triolein sonicates, serum very low density lipoproteins, high density lipoproteins, and nascent very low density lipoproteins. Insulin treatment of the diabetic rats reversed the I50 values to control. In studies on the site of inhibition of triglyceride synthesis in the overall biosynthetic pathway, serum very low density lipoproteins produced a concentration-dependent inhibition of liver cytosolic phosphatidate phosphohydrolase activity. A higher I50 value was obtained with the hepatic enzyme of the diabetic rats. This higher I50 value was reversed to control by insulin treatment of the diabetic rats. These results indicated that the activity of this enzyme was less sensitive to inhibition by very low density lipoproteins in the ketotic diabetic state. The reduced sensitivity of phosphatidate phosphohydrolase activity to triglyceride inhibition observed in the present studies could explain our previous observation of an increased rate of triglyceride synthesis in ketotic diabetic liver homogenates.
当酮症糖尿病大鼠的肝脏匀浆与[U-14C]-甘油3-磷酸及辅助因子一起孵育时，甘油三酯及其前体的合成增加。三油精超声处理物对甘油二酯和甘油三酯的合成产生浓度依赖性抑制，而单油精超声处理物则无作用。大鼠血清极低密度脂蛋白与三油精超声处理物一样，抑制甘油二酯和甘油三酯的合成。此外，极低密度脂蛋白的细胞内形式，即新生极低密度脂蛋白，也抑制甘油二酯和甘油三酯的合成。在酮症糖尿病大鼠的肝脏匀浆中，观察到三油精超声处理物、血清极低密度脂蛋白、高密度脂蛋白和新生极低密度脂蛋白对甘油三酯或甘油二酯合成的抑制具有更高的表观I50（产生50%活性抑制的抑制剂浓度）。对糖尿病大鼠进行胰岛素治疗可使I50值恢复至对照水平。在关于甘油三酯合成在整个生物合成途径中的抑制位点的研究中，血清极低密度脂蛋白对肝脏胞质磷脂酸磷酸水解酶活性产生浓度依赖性抑制。糖尿病大鼠的肝脏酶获得了更高的I50值。通过对糖尿病大鼠进行胰岛素治疗，这个更高的I50值恢复至对照水平。这些结果表明，在酮症糖尿病状态下，该酶的活性对极低密度脂蛋白的抑制不太敏感。在本研究中观察到的磷脂酸磷酸水解酶活性对甘油三酯抑制的敏感性降低，可以解释我们之前观察到的酮症糖尿病肝脏匀浆中甘油三酯合成速率增加的现象。
