Muscle fructose-2,6-bisphosphate and glucose-1,6-bisphosphate during insulin-induced hypoglycemia

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.