Ketone body turnover and net hepatic ketone production in fasted and diabetic dogs.

Abstract
Ketone body production rates were measured simultaneously by a tracer method and by an arteriovenous difference technique in conscious 48 h fasted normal dogs and in overnight fasted diabetic dogs after insulin withdrawal. During constant infusion of [3-14C]acetoacetate (AcAc) in fasted dogs, the mean tracer-determined total ketone production and the net hepatic ketone production rates were 11.4 .+-. 1.9 and 11.7 .+-. 1.5 .mu.mol/kg.min, respectively; the rates correlated significantly (P < 0.05) over a wide range of ketone production. Similarly, during infusion of D-[3-14C].beta.-hydroxybutyrate (.beta.OHB) in fasted dogs, the tracer-determined total ketone production correlated significantly (P < 0.01) with net hepatic ketone production rates. In diabetic dogs, the 2 techniques yielded total ketone production rates of 38.1 .+-. 5.6 and 34.4 .+-. 5.9 .mu.mol/kg.min, respectively. In all experiments, there was hepatic uptake of the infused ketone tracer and release of radioactive molecules of the other ketone. In ketotic diabetic dogs, increased rates of hepatic uptake and of interconversion were observed, whereas ketone utilization was decreased. Total ketone production rates as measured isotopically using [14C]AcAc or [14C].beta.OHB are in close agreement with the net hepatic ketone output regardless of the rates of ketone production; tracer-determined production rates of the individual ketone bodies AcAc and .beta.OHB are higher than their net hepatic production rates largely due to hepatic uptake and interconversion of the 2.

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