Amylin influences insulin-stimulated glucose metabolism by two
independent mechanisms.
Castle, Arthur L., Chia-Hua Kuo, and John L. Ivy.
Exercise Physiology and Metabolism Laboratory, Department of
Kinesiology and Health Education, University of Texas at Austin,
Austin, Texas 78712
APStracts 4:0202E, 1997.
The effects of amylin on fiber type specific muscle glucose metabolism
under hyperglycemic (10 mmol/L) and hyperinsulinemic (2.1 nmol/L)
conditions were investigated using a rat hind limb perfusion system.
Amylin concentration ranged from 1 to 100 nM. Efficacy for inhibition
of glucose uptake traced with 2-deoxyglucose by amylin was
demonstrated in all three fiber types. The incorporation of [3H] 2
-deoxyglucose tracer decreased from control values by 41 % in fast
oxidative (FO), 36 % in fast glycolytic (FG), and 37 % in slow
oxidative (SO) muscle with 100 nM amylin. Amylin increased
intracellular glucose-6-phosphate (G6P), and G6P was negatively
correlated with 2-deoxyglucose uptake in both FO (r = -0.65; p <
0.01) and FG (r = -0.53; p < 0.01) muscle. Muscle glycogen
concentration increased under control conditions and decreased in the
presence of 100 nM amylin. Lactate A-V efflux across the hind limb
increased significantly above control with 100 nM amylin (5.03 +/-
0.81 to 11.28+/- 0.94 [mu]mol x g-1 x hr-1). Cyclic AMP (cAMP)
increased in FO and FG muscle with amylin. Salmon calcitonin 8-32, an
amylin antagonist, ameliorated the effect of amylin on all responses
other than 2-deoxyglucose uptake and G6P concentration. These results
suggest that amylin may work through at least two independent
mechanisms, a cAMP mediated effect on glycogen metabolism and a non
-cAMP mediated inhibition of glycolysis.
Received 3 March 1997; accepted in final form 22 August 1997.
APS Manuscript Number E146-7.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 7 October 1997