GSK3 involvement in amylin signaling in isolated rat soleus muscle

Tatjana Abaffy, Garth J.S. Cooper

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

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 α:β isoforms in rat soleus was found to be 1.2:1. We found that amylin increased GSK3α activity, which in turn led to increased phosphorylation of glycogen synthase and decreased glycogen synthesis de novo.

Original languageEnglish (US)
Pages (from-to)2119-2125
Number of pages7
JournalPeptides
Volume25
Issue number12
DOIs
StatePublished - Dec 1 2004

Keywords

  • 2-deoxy-glucose
  • cAMP
  • CGRP
  • Glycogen

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Physiology
  • Cellular and Molecular Neuroscience

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