Regulation of muscle glycogen metabolism by CGRP and amylin: CGRP receptors not involved.
The aim of the present study was to determine whether amylin and calcitonin gene-related peptide (CGRP) act through shared or distinct receptors to inhibit insulin-stimulated incorporation of [14C]-glucose into glycogen. Rat amylin was 3 fold more potent than either rat alpha CGRP or rat beta CGRP at reducing glycogen synthesis from [14C]-glucose in insulin-treated rat soleus muscle. This action was blocked by peptide antagonists, with the rank order of potency being AC187 > salmon calcitonin8-32 (sCT8-32) > h-alpha CGRP8-37 for antagonism of either amylin or CGRP. The antagonist potency order correlated with affinity for amylin receptors measured in rat nucleus accumbens but not CGRP receptors measured in rat L6 muscle cells. Inhibition of glucose incorporation into glycogen by amylin and CGRP appears to be mediated by shared receptors that have the pharmacological characteristics of amylin receptors, and are distinct from previously described CGRP receptors.
Beaumont
K
K
Amylin Pharmaceuticals, Inc., San Diego, CA 92121, USA.
Pittner
R A
RA
Moore
C X
CX
Wolfe-Lopez
D
D
Prickett
K S
KS
Young
A A
AA
Rink
T J
TJ
D000682:Amyloid / Q000494:pharmacology*; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology; D058228:Islet Amyloid Polypeptide; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000187:drug effects*
D000682:Amyloid; D007004:Hypoglycemic Agents; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D018015:Receptors, Calcitonin Gene-Related Peptide; D006003:Glycogen; D005947:Glucose; D015740:Calcitonin Gene-Related Peptide