Stimulation of muscle glucose disposal by insulin in man is a function of
the preexisting plasma insulin concentration.
Vogt, Christoph, and Alexander S. Petrides.
Division of Gastroenterology, Department of Medicine, Heinrich-Heine
University of D[umlaut]usseldorf, 40225 D[umlaut]usseldorf, Germany, and
Division of Gastroenterology, Department of Medicine, The University of
Tennessee, Memphis, Memphis, Tennessee, 38163
APStracts 2:0012E, 1995.
To examine whether tissue sensitivity to insulin is dependent upon the
prevailing plasma insulin concentration, the ability of acute
hyperinsulinemia to stimulate glucose disposal was investigated in six normal
subjects before and after prolonged reduction of the plasma insulin
concentration. Glucose turnover ([6,6-2H2]-glucose), whole body glucose
oxidation and non-oxidative glucose disposal (indirect calorimetry), and
glycogen synthase activity in muscle were determined in the postabsorptive
and in the insulin-stimulated state (euglycemic hyperinsulinemic clamp: 3
mU/kg/min) before and after a 4 day subcutaneous infusion of the somatostatin
analogue octreotide (200 [mu]g/24 h). Constant octreotide infusion a)
decreased postabsorptive and meal-stimulated plasma insulin levels by 30-40%
but did not significantly alter overall glucose tolerance, FFA, growth hormone
and glucagon levels; b) was associated with significant increases in insulin
-mediated whole body glucose disposal (predrug: 10.29+/-0.49 vs postdrug:
11.42+/-0.72 mg/kg/min, p<0.04), non-oxidative glucose disposal (6.82+/-0.57
vs 7.68+/-0.62, p<0.03) and fractional glycogen synthase activity (0.14+/-0.03
vs 0.20+/-0.04 mU/mg protein, p<0.02). In contrast, infusing saline instead of
octreotide for 4 days to control subjects did not alter any of the metabolic
parameters. We conclude that lowering the plasma insulin concentration over a
prolonged period of time increases insulin sensitivity. The effects of
insulin to stimulate whole body glucose utilization, non-oxidative glucose
disposal and glycogen synthase activity in muscle are therefore functions of
the preexisting plasma insulin concentration.
Received 31 October 1994; accepted in final form 19 January 1995.
APS Manuscript Number E445-4RC.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 25 February 1995.