Mechanisms for development of diabetic hypertriglyceridemia in streptozotocin-treated rats. Effect of diet and duration of insulin deficiency.
A combined ultrastructural and functional approach was employed to define the effects of duration of diabetes and of diet on various aspects of lipid metabolism in rats with severe streptozotocin (SZ)-induced insulin deficiency. Plasma triglyceride (TG) levels rose to a mean of 479 mg/100 ml 24 h after SZ administration in rats eating a fat-free, high carbohydrate diet as compared to a mean of 324 mg/100 ml in rats eating a high fat diet. These changes were associated with a commensurate increase in hepatocyte Golgi very low density lipoprotein (VLDL) content, but only a small increase in estimates of VLDL-TG secretion rate (post-Triton WR 1339 increment in plasma TG level). Although these findings are consistent with the thesis that VLDL-TG synthesis and secretion are increased 24 h after administration of SZ, it seemed unlikely that the observed increase in VLDL-TG secretion could entirely account for the severity of the hypertriglyceridemia. Thus, although lipoprotein removal rate was not measured directly, it was necessary to postulate that a defect in VLDL-TG removal was also present at this stage. Hypertriglyceridemia was still present 7 days later, only in this instance plasma TG levels were higher in rats eating the high fat diet (a mean of 589 mg/100 ml, as compared to 263 mg/100 ml). Rats with diabetes of 7-day duration had a 50% decrease in both TG entry rate and hepatocyte Golgi complex VLDL content, irrespective of diet. Thus, there was no evidence of increased VLDL-TG secretion in chronic insulin deficiency. In this instance, although not assessed directly, it was necessary to postulate that the hypertriglyceridemia in chronically insulin-deficient rats is due entirely to a defect in lipoprotein removal, involving both dietary and endogenous fat.
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D003920:Diabetes Mellitus / Q000097:blood* / Q000139:chemically induced / Q000378:metabolism; D004032:Diet; D004040:Dietary Carbohydrates; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D006003:Glycogen; D006056:Golgi Apparatus / Q000648:ultrastructure; D007328:Insulin / Q000172:deficiency* / Q000627:therapeutic use; D008079:Lipoproteins, VLDL / Q000096:biosynthesis / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D008854:Microscopy, Electron; D051381:Rats; D013311:Streptozocin; D013997:Time Factors; D014280:Triglycerides / Q000097:blood* / Q000378:metabolism
D001786:Blood Glucose; D004040:Dietary Carbohydrates; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D008079:Lipoproteins, VLDL; D014280:Triglycerides; D013311:Streptozocin; D006003:Glycogen