Amylin-mediated inhibition of insulin-stimulated glucose transport in skeletal muscle
Castle, A.L.; Kuo, C.H.; Han, D.H.; Ivy, J.L.
American Journal of Physiology 275(3): E531-E536
1998
ISSN/ISBN: 0002-9513 PMID: 9725822 Document Number: 485719
We examined the effects of amylin on 3-O-methyl-D-glucose (3-O-MG) transport in perfused rat hindlimb muscle under hyperinsulinemic (350 muU/ml, 2,100 pmol/l) conditions. Amylin at 100 nmol/l concentration inhibited 3-O-MG transport relative to control in all three basic muscle fiber types. Transport decreased in slow-twitch oxidative (from 5.65 +- 1.13 to 3.46 +- 0.71 mumol cntdot g-1 cntdot h-1), fast-twitch oxidative (from 6.84 +- 0.90 to 4.84 +- 0.76 mumol cntdot g-1 cntdot h-1), and fast-twitch glycolytic (from 1.27 +- 0.20 to 0.60 +- 0.05 cntdot mumol cntdot g-1 cntdot h-1) muscle. Amylin inhibition of insulin-stimulated glucose transport in skeletal muscle was accompanied by a 433 +- 72% increase in intracellular glucose 6-phosphate (G-6-P) despite the absence of extracellular glucose. The source of hexose units for the formation and maintenance of G-6-P was likely glycogen. Amylin increased glycogenolysis, increased lactate formation, and decreased glycogen synthase activity. Furthermore, the kinetics of glycogen synthase suggest that this enzyme may control intracellular G-6-P concentration. Despite the large increase in G-6-P, no detectable increase in uridine diphosphate-N-acetylhexosamines occurred, suggesting that the proposed glucosamine pathway may not be involved in transport inhibition. However, decreases in uridine diphosphate hexoses were detected. Therefore, uridine or hexosamine-based metabolites may be involved in amylin action.