Triglyceride Metabolism in the Alloxan-Diabetic Rat

Abstract

Diabetes mellitus of graded severity was produced by withdrawing insulin from alloxan diabetic rats previously maintained on Protamine Zinc Insulin. The tissue distribution of H-3 palmitate-labeled chyle in the diabetic animals and in normal animals was compared fifteen minutes after its intravenous administration. Although hyperglycemia was apparent forty-eight hours after insulin withdrawal, it was only at seventy-two and ninety-six hours after insulin withdrawal that marked retention of radioactivity was apparent in blood and that adipose tissue, carcass and hepatic uptake of fatty acid was lower than normal. Lipoprotein lipase content of epididymal fat pads was significantly higher than normal in insulin-treated and lower than normal in the insulin-deprived rats. The findings indicate that insulin withdrawal in the alloxan diabetic rat results in delayed clearing of intravenously administered chylomicrons from blood. Initially this may be related in part to the defective uptake by adipose tissue which becomes depleted of lipoprotein lipase. More prolonged insulin deprivation, however, leads to a greatly expanded serum triglyceride pool which in itself could account for the markedly delayed clearing of chylomicrons in severe diabetes. DIABETES 16: 90-95, February, 1967. There are conflicting reports in the literature on the relationship between the clearing of dietary triglycerides and metabolism of carbohydrate. Fredrickson et al. 1 have claimed that carbohydrate feeding has no effect on the removal of intravenously administered chyle from the blood of dogs. Bierman and Hamlin 2 have claimed that insulin deprivation does not influence the rate of removal of C-14 labeled triglycerides from the blood of insulin-dependent human diabetics. On the other hand, Albrink and Man 3 have indicated that the degree of alimentary lipemia after a fat meal is less when the same amount of fat is fed with glucose and, more recently, Krut and Barsky 4 have claimed that From the

The Disappearance from the Circulation of Chylomicrons Obtained from Control and Diabetic Rats*

“…Other investigators have observed that the t Vfe of disappearance of triglyceride-labeled chylomicrons from the circulation of diabetic animals is increased (28)(29)(30), but as noted above, the site and mechanism for the removal of the triglyceride component of chylomicrons are very different from those for the sterol portion. However, Redgrave and Snibson (30) have reported that the clearance of [ 14 C]cholesterol-labeled lymph is also impaired in diabetic animals.…”

Mechanisms for Development of Diabetic Hypertriglyceridemia in Streptozotocin-Treated Rats EFFECT OF DIET AND DURATION OF INSULIN DEFICIENCY

“…Although hypertriglyceridemia is known to occur in association with severe insulin deficiency, questions remain as to the frequency of hypertriglyceridemia, the mechanisms responsible for its development, and the effect of diet on plasma triglyceride (TG)1 levels (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). Some confusion undoubtedly stems from the fact that studies of different experimental models of diabetes have yielded different insights as to the nature of diabetic hypertriglyceridemia.…”

Effect of clofibrate administration on plasma post-heparin lipolytic activity in man.

“…Of interest is the report of Eaton (1973) who showed that clofibrate admini stration to the rat for 10 days produced a significant increase in plasma glucagon, which is known to reduce plasma lipoproteins (Aubry et al 1974). It is also interesting that long-term clofibrate administration to the rat caused an increase in insulin sensitivity of adipose tissue (Weis et al 1973), since the insulin action in adipose tissue was shown to enhance synthesis of lipoprotein lipase in the tissue (Brown 1967). Thus, it is possible that the observed increase in PHLA might be produced through such effects of clofibrate on plasma glucagon and insulin sensiti vity in adipose tissue.…”