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.
Abaffy
Tatjana
T
School of Biological Sciences, Faculty of Science, University of Auckland, 3A Symonds Street, Private Bag 92019, Auckland 1001, New Zealand. tabaffy@newssun.med.miami.edu
Cooper
Garth J S
GJ
D000682:Amyloid / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology; D003847:Deoxyglucose / Q000378:metabolism; D006003:Glycogen / Q000096:biosynthesis / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D066298:In Vitro Techniques; D007333:Insulin Resistance / Q000502:physiology; D058228:Islet Amyloid Polypeptide; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology*; D051381:Rats
D000682:Amyloid; D058228:Islet Amyloid Polypeptide; D006003:Glycogen; D003847:Deoxyglucose; D000242:Cyclic AMP; D038362:Glycogen Synthase Kinase 3; D015740:Calcitonin Gene-Related Peptide