Studies on Lipid Metabolism in Experimental Diabetic Rat
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High frequency of hypercholesteremia in diabetics has often been reported, but today's knowledge concerning metabolic behaviour of cholesterol is not enough advanced.<BR>In the present investigation, significance of dietary cholesterol, its absorption, biosynthesis, elimination rate from blood and catabolism to bils acids were studied by using an alloxan diabetic rat. The high plasma cholesterol levels observed in diabetic rats were related to intake of dietary cholesterol.<BR>A possible explanation for this result could be obtained from cholesterol elimination and bile duct test by means of tracer cholesterol in which the decreased turnover rate of cholesterol was found.<BR>Alloxan diabetic rats were provided by a single intramuscular injection of 120 mg alloxan monohydrate per kg of body weight to normal animals, and the rats which gave more than 1/2% urine sugar on Tes-tape test for one week were used in these studies. Effect of dietary cholestero<BR>In the groups allowed to eat 1.12% cholesterol diet <I>ad libitum</I> for 10 days, the mean values in the normal and diabetic rats were 159.6±39.9 and 254.0±71.1 mg %, respectively. This result showed a significant difference (P<0.05), out in the groups fed on 0.12% cholesterol diet, no significant change was seen between the normal and diabetic rats. Similar results showing highe plasma cholesterol levels in diabetic rats fed on 1.12% cholesterol diet were confirmed again in another experiment in which restricted feeding of 15 and 10g per head daily was given. Plasma triglyceride and free fatty acid levels also iticreased in diabetic state, especially in the group fed on 1.12 % cholesterol diet. Absorption test of cholesterol<BR>After an oral administration of 2 μC <SUP>14</SUP>C-clsilegterol per 100g of body weight, radioactivities of lipid fraction at 2 and 4 hours were measured. No significant difference could be observed between the normal and diabetic rats. Biosynthesis of cholesterol <I>in vivo</I><BR>The abilities of cholesterol biosynthesis in both groups were compared by determining the radioactivities incorporated into liver cholesterol from <SUP>14</SUP>C-acetate given intraperitoneally 30 minutes prior to decapitation. Although the mean in the diabetic group showed a lower value than that observed in the normal group, no significant difference was present statistically owing to a relatively large standard error. A remarkable feed back control caused by high cholesterol diet was demonstrated in both normal and diabetic rats. Elimination test of cholesterol from blood<BR>Forty eight and 96 hours after an intraperitoneal injection of 1μC <SUP>14</SUP>C-cholesterol per 100 g of body weight, residual radioactivities in plasma were analyzed. It was noted that disappearance of radioactive cholesterol from plasma of the diabetic rats given 1.12% cholesterol diet was delayed significantly in comparison with the normal ones. Catabolism to bile acids<BR>In order to estimate the rate of bile acids formation from cholesterol, a bile duct was cannulated and the rats were allowed to stand for about 15 hours to avoid a surgical stress. The bile were collected at 4, 8, 12, 24, 34 and 48 hours after an intravenous injection of 1μC<SUP>14</SUP>C-cholesterol per 100g of body wight. The biles used for analysis in this experiment were obtained from the rats which survived over 10 hours after the collection period.<BR>The bile volume and its total radioactivities obtained from the diabetic rats were smaller by about 40% and 70%, respectively than that from the normal ones. A marked reduction in radioactivities of neutral sterol and bile acids, 80% and 65% respectively, were seen in the diabetic group. Conjugated form of bile acids, which were analyzed preliminarily, were separated into taurocholic acid, taurochenodeoxycholic acid and glycocholic acid by Frosch's thin layer chromatographic procedure.
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