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Exercise Physiology and Metabolism Laboratory, Department of Kinesiology and Health Education, University of Texas at Austin, Austin, Texas 78712
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 hindlimb 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
2-deoxy-[3H]glucose
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 (G-6-P), and
G-6-P 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 arteriovenous efflux across
the hindlimb increased significantly above control with 100 nM amylin
(5.03 ± 0.81 to 11.28 ± 0.94 µmol · g
1 · h1).
Adenosine 3',5'cyclic monophosphate (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 G-6-P
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.
skeletal muscle; glucose uptake; glucose 6-phosphate; glycogen
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