<p>This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</p> <p>Thiazolidinediones (TZD) have been shown to have
anti-diabetic effects including the ability to decrease
fasting hyperglycemia and hyperinsulinemia, increase
insulin-mediated glucose disposal rate (M)
and decrease hepatic glucose production, but the
mechanisms of action are not well established. To
determine whether a TZD (R-102380, Sankyo Company
Ltd., Tokyo, Japan) could improve insulin
action on skeletal muscle glycogen synthase (GS),
the rate-limiting enzyme in glycogen synthesis, 4
insulin-resistant obese monkeys were given I mg/kg/
day R-102380 p.o. for a 6-week period. Skeletal
muscle GS activity and glucose 6-phosphate (G6P)
content were compared between pre-dosing and
dosing periods before and during the maximal
insulin-stimulation of a euglycemic hyperinsulinemic
clamp.</p> <p>Compared to pre-dosing, insulin-stimulated GS
activity and G6P content were increased by this
TZD: GS independent activity (<italic>p</italic> = 0.02), GS total
activity (<italic>p</italic> =  0.005), GS fractional activity (<italic>p</italic> = 0.06)
and G6P content (<italic>p</italic> = 0.02). The change in GS
activity induced by <italic>in vivo</italic> insulin (insulin-stimulated
minus basal) was also increased by this TZD:
GS independent activity (<italic>p</italic> = 0.03) and GS fractional
activity (<italic>p</italic> = 0.04).</p> <p>We conclude that the TZD R-102380 improves
insulin action at the skeletal muscle in part by
increasing the activity of glycogen synthase. This
improvement in insulin sensitivity may be a key
factor in the anti-diabetic effect of the thiazolidinedione
class of agents.</p>
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Int J Exp Diabetes Res. 2000; 1(3):195-202