Insulin and hyperaminoacidemia regulate by a different mechanism
leucine turnover and oxidation in obesity.
Luzi, Livio, Pietro Castellino, and Ralph A. Defronzo.
Diabetes Division, Department of Medicine, University of Texas
Health Science Center and Audie L. Murphy Veteran's Memorial
Hospital, San Antonio, Texas and Department of Internal Medicine,
Radioactive and Stable Isotopes Laboratory, Istituto Scientifico San
Raffaele, University of Milan, Milano, Italy
APStracts 2:0193E, 1995.
Seven normal glucose tolerant obese subjects (IBW=161%) and 18
controls (IBW=102%) were studied with the euglycemic insulin clamp
(10 and 40 mU. m-2.min-1) technique, the 14C-leucine infusion and
indirect calorimetry to examine if the insulin resistance with
respect to glucose metabolism extends to amino acid/protein
metabolism. In the basal state total plasma amino acid and leucine
concentrations, endogenous leucine flux (ELF), leucine oxidation
(LO), and non-oxidative leucine disposal (NOLD) were similar in obese
and control subjects. During both low (10 mU.m-2.min-1) and higher
(40 mU.m-2.min-1) dose insulin clamp studies, insulin-mediated
glucose uptake was reduced in obese versus control subjects
(p<0.01). During the last hour of the higher dose insulin clamp
step, the decrease in total plasma amino acids, branched chain amino
acids and leucine concentration was impaired in obese vs control
subjects (p<0.01). However, suppression of ELF and NOLD was
similar in both groups. During the low-dose insulin clamp the
decrease in plasma leucine concentration, LO, and ELF all were
impaired (p<0.01). A second study was performed where the total
plasma amino acid concentration was increased 2-3 fold in both
groups. Under these conditions of low plasma insulin/high amino acid
levels, LO and NOLD increased similarly in obese and control
subjects. In conclusion, insulin resistance is a common feature of
both glucose and protein metabolism in obesity. The defect in protein
metabolism is characterized by an impairment of the ability of
insulin to inhibit proteolysis; the stimulatory effect of
hyperaminoacidemia on protein synthesis is intact in obesity.
Received 7 March 1995; accepted in final form 11 September 1995.
APS Manuscript Number E105-5.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 31 October 95