Journal of Applied Physiology, Vol 76, Issue 2 853-858, Copyright © 1994 by American Physiological Society
Muscle fructose-2,6-bisphosphate and glucose-1,6-bisphosphate during insulin-induced hypoglycemia
W. W. Winder, J. M. Carling, C. Duan, J. P. Jones, S. L. Palmer and M. C. Walker
Zoology Department, Brigham Young University, Provo, Utah 84602.
Glucose production during insulin-induced hypoglycemia in the fasted state
is heavily dependent on the process of hepatic gluconeogenesis. Skeletal
muscle glycogen is one possible source of lactate for hepatic
gluconeogenesis. Fructose 2,6-bisphosphate (F-2,6-P2) and glucose
1,6-bisphosphate (G-1,6-P2) are two allosteric activators of muscle
glycolysis. To investigate their putative role in the control of muscle
lactate production during hypoglycemia, fasted rats were infused via
jugular catheters with insulin in 0.9% NaCl or with 0.9% NaCl alone for 60
or 120 min. Muscles were removed and clamp frozen in liquid nitrogen. The
insulin infusion produced plasma insulin values of 97 +/- 13 microU/ml
after 1 h and 100 +/- 9 microU/ml after 2 h. Blood glucose in the
saline-infused rats was 4.6 +/- 0.2 mM after 1 h and 5.1 +/- 0.1 mM after 2
h compared with 1.5 +/- 0.01 and 1.0 +/- 0.1 mM after 1 and 2 h,
respectively, in the insulin-infused rats. The hypoglycemic rats had
significantly elevated plasma epinephrine and blood lactate levels compared
with the saline-infused rats. F-2,6-P2 and G-1,6-P2 were increased two- to
five-fold in white quadriceps of hypoglycemic rats compared with that of
saline-infused rats. The results are consistent with F-2,6-P2 and G-1,6-P2
playing a role in stimulating muscle lactate production as a source of
gluconeogenic substrate during insulin-induced hypoglycemia.
