GSK3 involvement in amylin signaling in isolated rat soleus muscle

Amylin can evoke insulin resistance by antagonizing insulin in a non-competitive manner. Here. we investigated the glycogenolytic effect of amylin in isolated skeletal muscle and compared it to the effects of a calcitonin gene-related peptide (CGRP). Amylin alone had no statistically significant effect on glucose transport. However, amylin decreased insulin-stimulated glucose transport by about 30%. The involvement of cAMP could not be detected at the concentrations shown to promote glycogenolysis. Previously. it has been shown that increased glycogen synthase kinase 3 (GSK3) activity plays a role in insulin resistance. Here. the ratio of GSK3 alpha:beta isoforms in rat soleus was found to be 1:2:1. We found that amylin increased GSK3alpha activity, which in turn led to increased phosphorylation Of glycogen synthase and decreased glycogen synthesis de novo. (C) 2004 Elsevier Inc. All rights reserved.