AJP - Endocrinology and Metabolism, Vol 263, Issue 2 E261-E267, Copyright © 1992 by American Physiological Society
Forearm ketone body metabolism in normal and in insulin-dependent diabetic patients
A. Avogaro, A. Doria, L. Gnudi, A. Carraro, E. Duner, E. Brocco, A. Tiengo, G. Crepaldi, D. M. Bier and R. Nosadini
Institute of Clinical Medicine, University of Padua, Italy.
In insulin deficiency, there is excessive arterial delivery of free fatty
acid (FFA) to muscles where they are converted to acetoacetyl-CoA and
acetyl-CoA. These intermediates may be metabolized further to acetoacetate
and beta-hydroxybutyrate, which can be released into the venous
circulation. When ketone body (KB) tracers are infused in vivo, they are
diluted across muscle tissue. This dilution may be due to 1) KB newly
formed within muscle (ketogenesis); 2) exchange of tracer between labeled
and unlabeled acetyl-CoA and acetoacetyl-CoA, intermediates common to the
metabolism of both FFA and KB (pseudoketogenesis). Thus this study assessed
whether such label exchange could be detected across the human forearm and
whether an increased delivery of FFA in insulin-sufficient controls
provoked dilution of labeled KB tracer comparable to that observed in
insulin-deficient diabetics. Five normal and five insulin-dependent
diabetic (IDDM) subjects were infused with labeled [3,4-13C2]-acetoacetate.
[13C]KB enrichments were lower in forearm vein than in the artery, and
dilution of labeled KB was always higher than that which could be explained
by arterial-venous differences of unlabeled KB. When arterial FFA
concentrations in normals were raised (Intralipid+heparin) to values
comparable to those of the diabetics, no additional increase in forearm
arteriovenous dilution of labeled KB was observed. Neither in the basal
state nor under conditions of increased plasma FFA were we able to detect
venous appearance of KB labeled in the first and in the second carbon
atoms, a necessary consequence of pseudoketogenesis.(ABSTRACT TRUNCATED AT
250 WORDS)
