Uptake of β-hydroxybutyrate in perfused hindquarter of starved and diabetic rats

To elucidate the peripheral ketone body uptake and the role of insulin in regulating peripheral ketone body utilization in starvation and diabetes mellitus, uptake of β-hydroxybutyrate (BOHB) was investigated in the perfused hindquarter of starved (72 hour) or streptozotocin-induced (65 mg/kg, intraperitoneally) diabetic rats. Blood concentration of BOHB was significantly higher in diabetic (1,380 ± 250 μmol/L) and starved (1,229 ± 245 μmol/L) rats than in controls (104 ± 8 μmol/L). The hindquarter was perfused with synthetic medium at a flow rate of 0.5 mL/g muscle weight/min. BOHB was added to the medium at a concentration of 0.1, 0.5, 2, or 10 mmol/L, and insulin was added at a concentration of 20, 100, or 500 μU/mL. In the hindquarter perfused with 0.1, 0.5, 2, or 10 mmol/L BOHB, fractional uptake of BOHB in the absence or presence of insulin was significantly lower in diabetic and starved rats than in controls. The addition of 100 or 500 μU/mL insulin significantly increased BOHB uptake in the perfused hindquarter of control rats; however, insulin addition did not significantly increase BOHB uptake in the perfused hindquarter of starved and diabetic rats. These results suggest that BOHB uptake is markedly reduced in the perfused hindquarter of starved and diabetic rats, and that physiological dose of insulin stimulates BOHB uptake in control rats, but not in starved and diabetic rats.