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 amylin signal transduction in isolated strips of soleus muscle. Rat amylin, 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 added phosphodiesterase inhibitor. The EC50 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 that seen with a maximally effective concentration of epinephrine (1 microM) under the same conditions. Consistent with the observed rise in cAMP there was an increase in glycogen phosphorylase a (EC50 2.2 nM +/- 0.25 log units), decreased glycogen content (EC50 0.9 nM +/- 0.22 log units) and enhanced production of lactate (EC50 1.5 nM +/- 0.33 log units). These data support the concept that amylin promotes glycogenolysis in skeletal muscle and enhances production of lactate through glycolysis as a result of activation of Gs coupled receptors, stimulation of adenylate cyclase, elevation of cAMP levels and activation of glycogen phosphorylase.
Pittner
R
R
Amylin Pharmaceuticals, Inc., San Diego CA 92121-3027, USA.
Beaumont
K
K
Young
A
A
Rink
T
T
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000682:Amyloid / Q000494:pharmacology*; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D006003:Glycogen / Q000378:metabolism; D066298:In Vitro Techniques; D058228:Islet Amyloid Polypeptide; D007773:Lactates / Q000378:metabolism*; D019344:Lactic Acid; D008297:Male; D009132:Muscles / Q000187:drug effects* / Q000378:metabolism; D006005:Phosphorylases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000682:Amyloid; D058228:Islet Amyloid Polypeptide; D007773:Lactates; D019344:Lactic Acid; D006003:Glycogen; D000242:Cyclic AMP; D006005:Phosphorylases; D015056:1-Methyl-3-isobutylxanthine