Effect of short-term consumption of a high-fat, low-carbohydrate diet on metabolic control in insulin-deficient diabetic rats

This study examined the effect of changing the proportion of dietary fat on metabolic control in rats rendered mildly diabetic with streptozotocin (STZ). The high-fat (HF) diet contained 66% energy as fat and 12% as carbohydrate while the low-fat (LF) diet contained 12% energy as fat and 66% as carbohydrate. Both diets had a P S ratio of 1:3. Young male rats weighing 100 g were treated with STZ (60 mg/kg IV) and randomly allocated to either the LF of HF diet. After 2 weeks, the fasting plasma glucose concentrations were significantly higher in the HF-STZ rats than in the LF-STZ rats (13.2 ± 1.2 mmol/L v 7.1 ± 0.8 mmol/L, respectively, P < 0.001). The increase in plasma glucose above the basal level following the intravenous glucose load (0.5 g/kg body wt) was similar in both groups of STZ-treated rats and glucose clearance was similarly impaired. The fall in glucose concentrations in the 30 minutes following the IV insulin (0.5 U Actrapid insulin/kg body wt) was greater in the LF-STZ rats (ΔAUC = − 1.60 ± 0.20 mmol/L 0.5h) than in the HF-STZ group (ΔAUC = −0.97 ± 0.20 mmol/L 0.5 h, P < 0.05) and either of the control groups (ΔAUC = −0.94 ± 0.37, −0.83 ± 0.09 mmol/L 0.5 h for LF and HF rats, respectively, P < 0.05). Furthermore, in vitro glucose utilization was higher in soleus muscle of both LF-STZ and HF-STZ rats relative to controls and sensitivity to insulin of this process was normal in the diabetic animals. Hepatic glucokinase activity was markedly reduced in HF-STZ rats compared to LF-STZ rats. These results suggest that peripheral insulin sensitivity and glucose utilization are not impaired in the STZ-treated rats and that the more severe deterioration in glucose tolerance in the HF diabetic rats may have been due to increased hepatic glucose production.