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-kinase by fructose 2,6-bisphosphate (F-2,6-P2). To determine if a correlation exists between F-2,6-P2 and lactate production in skeletal muscle, isolated rat hindlimbs were perfused for 30 min with a medium containing epinephrine at concentrations varying between 1.7 +/- 0.5 and 72.4 +/- 4.2 nM. In comparison to control values, hindlimbs perfused with 72.4 +/- 4.2 nM epinephrine had a two- to threefold increase in F-2,6-P2 and a fourfold increase in muscle lactate production. Hindlimb lactate production was highly correlated to gastrocnemius adenosine 3',5'-cyclic monophosphate (r = 0.80), fructose 6-phosphate (r = 0.87), and F-2,6-P2 (r = 0.81). The adenosine 3',5'-cyclic monophosphate-mediated 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-P2 and muscle lactate production at varying concentrations of epinephrine supports the hypothesis that the epinephrine-induced activation of glycolysis and lactate production in nonexercising muscle is mediated in part by increases in F-2,6-P2 levels.
Jones
J P
JP
Zoology Department, Brigham Young University, Provo, Utah 84602.
MacLean
P S
PS
Winder
W W
WW
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D004837:Epinephrine / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005635:Fructosediphosphates / Q000096:biosynthesis*; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D006614:Hindlimb / Q000098:blood supply / Q000378:metabolism; D066298:In Vitro Techniques; D007328:Insulin / Q000097:blood; D007773:Lactates / Q000096:biosynthesis*; D019344:Lactic Acid; D008297:Male; D009132:Muscles / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D010732:Phosphofructokinase-1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects
D005230:Fatty Acids, Nonesterified; D005635:Fructosediphosphates; D007328:Insulin; D007773:Lactates; D019344:Lactic Acid; C027652:fructose 2,6-diphosphate; D006003:Glycogen; D000242:Cyclic AMP; D010732:Phosphofructokinase-1; D005947:Glucose; D004837:Epinephrine