The interaction of carbohydrate and fat fuels in human skeletal
muscle: impact of obesity and niddm.
Mandarino, Lawrence J., Agostino Consoli, Avanindra Jain, and David E.
Kelley.
The Departments of Medicine and Biochemistry, Division of Diabetes,
The University of Texas Health Science Center at San Antonio, The
Department of Medicine, University of Pittsburgh, and The Department
of Veterans Affairs Medical Center, Pittsburgh
APStracts 2:0228E, 1995.
The capability to select between lipid and carbohydrate for oxidative
energy production is a fundamental property of skeletal muscle. It is
generally accepted that an abundance of FFA will dictate that
skeletal muscle preferentially utilizes lipid. A mechanism that
underlies this behavior, the inhibition of the activity of the
pyruvate dehydrogenase complex (PDHC), has been described in detail.
The converse of this, the ability of glucose to promote its own
metabolism, is less well-characterized. The current study was
undertaken to examine the impact which obesity and NIDDM have on the
ability of glucose to stimulate its own uptake and oxidation in
muscle. Euglycemic and hyperglycemic clamp experiments were performed
with somatostatin infusions so that insulin could be replaced to
basal levels or to physiological hyperinsulinemia. Arterio-venous leg
balance methods were used to measure the pathways of leg muscle
glucose uptake, oxidation, and storage. Percutaneous biopsies of the
vastus lateralis muscle were taken to determine PDHC or glycogen
synthase (GS) activities. During basal insulin replacement, obese as
compared to lean nondiabetic subjects had higher values for glucose
uptake, RQ, and glucose oxidation (all P<0.05) and a higher
proportion of leg energy expenditure derived from glucose. Obese NIDD
patients had a greater reliance on fat calories than lean diabetics
during basal insulin replacement (P<0.05). Hyperinsulinemia
increased leg glucose metabolism (P<0.001) in all groups, but
obese NIDD patients were significantly more insulin resistant.
Hyperglycemia in NIDDM compensated for insulin resistance to the
extent that rates of glucose metabolism were the same as nondiabetics
studied at euglyemia. When nondiabetics were studied at hyperglycemia
matched to the diabetics, the insulin resistance was still readily
apparent.
Received 4 August 1995; accepted in final form 2 November 1995.
APS Manuscript Number E368-5.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 30 November 95