AJP - Regulatory, Integrative and Comparative Physiology, Vol 260, Issue 1 113-R119, Copyright © 1991 by American Physiological Society
Relationship between carbohydrate oxidation and G-1,6-P2 in human skeletal muscle during euglycemic hyperinsulinemia
A. Katz and C. Bogardus
Department of Kinesiology, University of Illinois, Urbana 61801.
Euglycemic (approximately 5.5 mM) hyperinsulinemic clamps were performed on
normoglycemic insulin-sensitive (NIS) men and men who were normoglycemic
but insulin resistant (NIR) and hyperglycemic and insulin resistant (HIR)
(i.e., noninsulin-dependent diabetes mellitus). Insulin was infused at
successive rates of 40 and 400 mU.m-2.min-1, and biopsies were obtained
from the quadriceps femoris muscles before and after insulin and analyzed
for regulators of phosphofructokinase, a rate-limiting enzyme for
glycolysis. Glucose disposal and whole body carbohydrate oxidation were
markedly lower in NIR and HIR vs. NIS (P less than 0.001 for disposal and
oxidation). The alpha-D-glucose 1,6-bisphosphate (G-1,6-P2) content
increased almost twofold during the 40-mU insulin infusion (P less than
0.001) without any further change during the 400-mU infusion in NIS men.
The increase in G-1,6-P2 in NIR and HIR was only approximately 25 and 50%
of the increase observed in NIS during the 40- and 400-mU infusions,
respectively. The mean content of G-1,6-P2 was strongly related to the mean
rate of carbohydrate oxidation (r = 0.99; P less than 0.001). Because
during euglycemic hyperinsulinemia approximately 90% of the glucose
utilization is accounted for by skeletal muscle (J. Clin. Invest. 76: 149,
1985), it is likely that whole body carbohydrate oxidation is proportional
to carbohydrate oxidation and glycolysis in muscle. The different rates of
carbohydrate oxidation between NIS and insulin-resistant men could not be
associated with differences in fructose 6-phosphate, fructose
1,6-bisphosphate, fructose 2,6-bisphosphate, Pi, free ADP and free AMP
(activators of phosphofructokinase), or ATP and citrate (inhibitors of
phosphofructokinase).
