Affiliation:
1. Metabolism Division, Department of Medicine, Washington University School of Medicine St. Louis, Missouri
Abstract
The present study was undertaken to determine whether alterations in ketone body utilization and hepatic production, independent of the FFA load, were also involved in the development of fasting ketosis.
Plasma /β/-OH butyric acid (β-OHB) increased to 2.5-4.5 mM and plasma FFA to 1,000-1,400 μEq/L. in normal weight individuals after five to seven days' starvation and in obese subjects after ten to fourteen days' fasting. Acute elevations of the plasma FFA > 1,500 μEq/L. for sixty minutes in fed normal weight and obese subjects with a fat meal-heparin regimen resulted in peak elevations of plasma β-OHB (0.25-0.45mM), only 10 per cent of that seen during fasting. When plasma FFA were lowered acutely during fasting with the antilipolytic agent Pyrazole to control levels (400-600 μEq/L.), plasma β-OHB decreased 35 ± 5 per cent. Comparable lowering of plasma FFA in normal weight or obese starved subjects given dexamethasone to maintain elevated fasting plasma insulin levels resulted in an 87 ± 3 per cent decrease in plasma β-OHB. Similar studies in obese fasted subjects pretreated with an intravenous infusion of insulin (1.0 U/hr. for eight hours) before receiving Pyrazole resulted in a 65 ± 5 per cent decrease in plasma β-OHB.
Plasma β-OHB half-life, determined after injections of 12 gm. (β-OHB, increased significantly during fasting (110 ± 15 minutes) and was decreased when the fasting subjects were maintained on dexamethasone (65 ± 7 minutes).
These studies indicate that accelerated hepatic ketogenesis during starvation is a result of both enhanced activity of the enzymatic system(s) involved in ketone body production as well as an increased FFA load. The increase in plasma,(β-OHB during fasting reflects not only an accelerated rate of hepatic ketogenesis but also an impairment of peripheral utilization, both processes apparently being sensitive to insulin.
Publisher
American Diabetes Association
Subject
Endocrinology, Diabetes and Metabolism,Internal Medicine
Cited by
23 articles.
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