Lactate production from the rat hindlimb is increased after glucose administration and is suppressed by a selective amylin antagonist: evidence for action of endogenous amylin in skeletal muscle.
By serially measuring blood flow and venous-arterial lactate differences across the hindlimb of the fasted anesthetized rat, we examined (1) whether exogenous amylin increased muscle lactate production in vivo, (2) whether glucose administration increased muscle lactate production, and (3), by using the selective amylin antagonist AC187 to block endogenous peptide, whether amylin secreted in response to glucose could mediate muscle lactate production. Abdominal aortic flow was unchanged by any treatment. Hindlimb lactate production was increased by both 100 micrograms s.c. amylin (4.0 +/- 0.4 cf 2.6 +/- 0.3 mumol/min after saline, P < 0.05) and by infusion of 2mmol D-glucose (3.0 +/- 0.2 cf 2.3 +/- 0.2 mumole/hr after saline, P < 0.03). The increase in hindlimb lactate production was prevented by infusion of AC187 (mean post-treatment venoarterial delta-lactate 140 +/- 11 microM; n.s. vs saline-treated delta-lactate 154 +/- 10 microM; P < 0.05 vs glucose-treated delta-lactate 201 +/- 14 microM). These findings are consistent with endogenous amylin secreted in response to a glucose challenge having acted at skeletal muscle to release lactate.
D000682:Amyloid / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001158:Arteries; D005947:Glucose / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D006614:Hindlimb; D007262:Infusions, Intravenous; D058228:Islet Amyloid Polypeptide; D007700:Kinetics; D007773:Lactates / Q000097:blood / Q000378:metabolism*; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D010446:Peptide Fragments; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow; D014680:Veins
D000682:Amyloid; D058228:Islet Amyloid Polypeptide; D007773:Lactates; D010446:Peptide Fragments; D010455:Peptides; C087166:AC 187; D005947:Glucose