Effects of Dietary Composition on Adipose Tissue Hexokinase-II and Glucose Utilization in Normal and Streptozotocin-diabetic Rats

Abstract

The control of adipose tissue hexokinase isoenzymes in response to altered dietary composition was investigated. Rats that were fasted and then refed carbohydrate-free diets increased their HK-II activity in epididymal fat pads above the level in fasted animals. However the ultimate activity of HK-II achieved during refeeding with seven diets of varying composition was dependent mainly on dietary carbohydrate; the effect of dietary carbohydrate overcame poor growth due to protein deficiency or decreased food intake. Fat pads from animals fed for three weeks from weaning with 19 per cent protein diets showed a marked increase in HK-II on 51 per cent carbohydrate over those on a carbohydrate-free diet but no further increase on 81 per cent carbohydrate. However, adipocytes from rats on 81 per cent carbohydrate had significantly higher HK-II than those from rats on 51 per cent carbohydrate. In streptozotocin-diabetic rats there was no difference in adipose tissue HK-II between rats on 19 per cent protein-51 per cent carbohydrate and those on 19 per cent protein carbohydrate-free diets. Treatment of diabetic rats with 3 U. lente insulin daily brought HK-II into the range for normal rats, but once again there was no difference between the two diets. The treated rats showed marked weight gain but were still hyperglycemie. Adipocytes from rats on the 19 per cent protein carbohydrate-free diet showed lower HK-II and glucose conversion to CO2 and triglyceride than adipocytes from rats on the 51 per cent carbohydrate diet. There was a high correlation of HK-II to both pathways of glucose utilization on both diets. However, the slope of the regression line of triglyceride production on HK-II was much lower on the carbohydrate-free than on the basal diet. Adipocytes from rats on the 81 per cent carbohydrate diet had HK-II activity and glucose utilization that fell within the 95 per cent confidence limits for the relationship derived from adipocytes from rats on the 51 per cent carbohydrate diet. Values for glucose utilization in adipocytes from treated diabetic rats on the carbohydrate-free diet were above the expected range for this diet for both CO2 and triglyceride production; CO2 production was also above the expected range for diet in treated diabetic rats on the 51 per cent carbohydrate diet. Glucose conversion to both end products was higher for a given level of HK-II in the treated diabetic animals on the 51 per cent carbohydrate diet than on the carbohydrate-free diet. These data indicate that diet has a major effect on HK-II that is probably mediated by carbohydrate and is dependent on insulin. Although there appears to be a relationship between HK-H and glucose utilization in a given diet-and-treatment group, there is a departure from the normal relationship in adipocytes from rats on a high-fat carbohydrate-free diet or from partially treated diabetic rats.