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 differenc es 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 productio n, and (3), by using the selective amylin antagonist AC187 to block en dogenous peptide, whether amylin secreted in response to glucose could mediate muscle lactate production. Abdominal aortic flow was unchange d by any treatment. Hindlimb lactate production was increased by both 100 mu g s.c. amyiin (4.0+/-0.4 cf 2.6+/-0.3 mu mol/min after saline, P<0.05) and by infusion of 2mmol D-glucose (3.0+/-0.2 cf 2.3+/-0.2 mu mole/hr after saline, P<0.03). The increase in hindlimb lactate produc tion was prevented by infusion of AC187 (mean post-treatment venoarter ial Delta-lactate 140+/=11 mu M; n.s. vs saline-treated Delta-lactate 154+/-10 mu M; P<0.05 vs glucose-treated Delta-lactate 201+/-14 mu M). These findings are consistent with endogenous amylin secreted in resp onse to a glucose challenge having acted at skeletal muscle to release lactate. (C) 1995 Academic Press. Inc.