MUSCLE FRUCTOSE-2,6-BISPHOSPHATE AND GLUCOSE-1,6-BISPHOSPHATE DURING INSULIN-INDUCED HYPOGLYCEMIA

Glucose production during insulin-induced hypoglycemia in the fasted s tate is heavily dependent on the process of hepatic gluconeogenesis. S keletal muscle glycogen is one possible source of lactate for hepatic gluconeogenesis. Fructose 2,6-bisphosphate (F-2,6-P-2) and glucose 1,6 -bisphosphate (G-1,6-P-2) are two allosteric activators of muscle glyc olysis. To investigate their putative role in the control of muscle la ctate production during hypoglycemia, fasted rats were infused via jug ular catheters with insulin in 0.9% NaCl or with 0.9% NaCl alone for 6 0 or 120 min. Muscles were removed and clamp frozen in liquid nitrogen . The insulin infusion produced plasma insulin values of 97 +/- 13 mu U/ml after 1 h and 100 +/- 9 mu U/ml after 2 h. Blood glucose in the s aline-infused rats was 4.6 +/- 0.2 mM after 1 h and 5.1 +/- 0.1 mM aft er 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 s ignificantly elevated plasma epinephrine and blood lactate levels comp ared with the saline-infused rats. F-2,6-P-2 and G-1,6-P-2 were increa sed two- to five-fold in white quadriceps of hypoglycemic rats compare d with that of saline-infused rats. The results are consistent with F- 2,6-P-2 and G-1,6-P-2 playing a role in stimulating muscle lactate pro duction as a source of gluconeogenic substrate during insulin-induced hypoglycemia.