Effect of insulin and contraction on glycogen synthase phosphorylation and kinetic properties in epitrochlearis muscles from lean and obese Zucker rats

Fang Chin Lin, Yu Chiang Lai, Astrid Bolling, Jorid T. Stuenaes, Kristoffer T. Cumming, Ada Ingvaldsen, John L. Ivy, Jorgen Jensen

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

In the present study, the effects of insulin and contraction on glycogen synthase (GS) kinetic properties and phosphorylation were investigated in epitrochlearis muscles from lean and obese Zucker rats. Total GS activity and protein expression were ~15% lower in epitrochlearis from obese rats compared with lean rats. Insulin-stimulated GS fractional activity and affinity for UDP-glucose were lower (higher Km) in muscles from obese rats. GS Ser641 and Ser645,649,653,657 phosphorylation was higher in insulin-stimulated muscles from obese rats, which agreed with lower GS activation. Contraction-mediated GS dephosphorylation of Ser641, Ser641+645, Ser645,649,653,657, and Ser7+10 was normal in muscles from obese Zucker rats, and GS fractional activity increased to similar levels in epitrochlearis muscles from lean and obese rats. GS affinity for UDP glucose was ~0.8, ~0.4, and ~0.1 mM with assay buffers containing 0, 0.17, and 12 mM glucose 6-phosphate, respectively. Contraction increased affinity for UDP-glucose (reduced Km) at a physiological concentration of glucose 6-phosphate (0.17 mM) to ~0.2 mM in muscles from both lean and obese rats. Interestingly, in the absence of glucose 6-phosphate in the assay buffer, contraction (and insulin) did not influence GS affinity for UDP-glucose, indicating that affinity is regulated by sensitivity for glucose 6-phosphate. In conclusion, contraction-mediated activation and dephosphorylation of GS were normal in muscles from obese Zucker rats, whereas insulin-mediated GS activation and dephosphorylation were impaired.

Original languageEnglish
Pages (from-to)C1539-C1547
Number of pages9
JournalAmerican Journal of Physiology - Cell Physiology
Volume302
Issue number10
DOIs
Publication statusPublished - 15 May 2012

Keywords

  • AMPK
  • Diabetes
  • Enzyme kinetic
  • GSK-3
  • Insulin resistance

ASJC Scopus subject areas

  • Cell Biology
  • Physiology

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