DOSE-DEPENDENT ELEVATION OF CYCLIC-AMP, ACTIVATION OF GLYCOGEN-PHOSPHORYLASE, AND RELEASE OF LACTATE BY AMYLIN IN RAT SKELETAL-MUSCLE

We report here our investigation of the role of cyclic AMP (cAMP) in a mylin signal transduction in isolated strips of soleus muscle. Rat amy lin, at 100 nM, increased cAMP levels, from 0.431 +/- 0.047 to a peak of 1.24 +/- 0.01 pmol cAMP/mg wet wt. after 5 min, in the absence of a dded phosphodiesterase inhibitor. The EC(50) of the response was 0.48 nM (+/- 0.12 log units) in the absence of insulin and 0.3 nM (+/- 0.18 log units) in the presence of 7.1 nM insulin. The response seen with a maximally effective concentration of amylin (10 nM) was similar to t hat seen with a maximally effective concentration of epinephrine (1 mu M) under the same conditions. Consistent with the observed rise in cA MP there was an increase in glycogen phosphorylase a (EC(50) 2.2 nM +/ - 0.25 log units), decreased glycogen content (EC(50) 0.9 nM +/- 0.22 log units) and enhanced production of lactate (EC(50) 1.5 nM +/- 0.33 log units). These data support the concept that amylin promotes glycog enolysis in skeletal muscle and enhances production of lactate through glycolysis as a result of activation of Gs coupled receptors, stimula tion of adenylate cyclase, elevation of cAMP levels and activation of glycogen phosphorylase.