CORRELATION BETWEEN FRUCTOSE 2,6-BISPHOSPHATE AND LACTATE PRODUCTION IN SKELETAL-MUSCLE

The epinephrine-induced production of lactate in nonexercising muscles may be due in part to allosteric activation of 6-phosphofructo-1-kina se by fructose 2,6-bisphosphate (F-2,6-P-2). To determine if a correla tion exists between F-2,6-P-2 and lactate production in skeletal muscl e, isolated rat hindlimbs were perfused for 30 min with a medium conta ining epinephrine at concentrations varying between 1.7 +/- 0.5 and 72 .4 +/- 4.2 nM. In comparison to control values, hindlimbs perfused wit h 72.4 +/- 4.2 nM epinephrine had a two- to threefold increase in F-2, 6-P-2 and a fourfold increase in muscle lactate production. Hindlimb l actate production was highly correlated to gastrocnemius adenosine 3', 5'-cyclic monophosphate (r = 0.80), fructose 6-phosphate (r = 0.87), a nd F-2,6-P-2 (r = 0.81). The adenosine 3',5'-cyclic monophosphate-medi ated increase in glycogenolysis with consequent increase in fructose 6 -phosphate (substrate for 6-phosphofructo-1-kinase and 6-phosphofructo -2-kinase) is likely important for induction of lactate production by inactive muscle. The high correlation between muscle F-2,6-P-2 and mus cle lactate production at varying concentrations of epinephrine suppor ts the hypothesis that the epinephrine-induced activation of glycolysi s and lactate production in nonexercising muscle is mediated in part b y increases in F-2,6-P-2 levels.