Metabolism of ketone bodies by skeletal muscle in starvation and uncontrolled diabetes.

Abstract Previous studies have suggested that skeletal muscle may be responsible for as much as 25% of ketone body (KB) production in poorly controlled diabetes. In the present studies, acetoacetate (AcAc) and β-hydroxybutyrate production was quantitated in the canine hindlimb from surgically placed arterial and venous catheters in conscious insulin-withdrawn diabetic (n = 5) and 4-day fasted (n = 7) dogs. A two-pool modeling technique, using simultaneous infusions of 13 C acetoacetate and 14 C β-hydroxybutyrate (βOHB) was employed to quantitate total body and hindlimb KB kinetics. Total KB production was 9.4 and 39.3 μmol · kg −1 · min −1 in the fasted and diabetic animals, respectively. Hindlimb KB production was negligible in both groups. The two-pool model estimates of hindlimb KB utilization were similar to the values obtained by an arterial-venous difference calculation. In conclusion, the hindlimb does not contribute to de novo synthesis of KBs in either fasted or diabetic dogs. Since species differences in KB metabolism occur, it is possible that muscle may be a site for KB production in humans.