Levodopa with carbidopa diminishes glycogen concentration, glycogen synthase activity, and insulin-stimulated glucose transport in rat skeletal muscle

Jill L. Smith, Jeong Sun Ju, Bithika M. Saha, Brad A. Racette, Jonathan S. Fisher

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

We hypothesized that levodopa with carbidopa, a common therapy for patients with Parkinson's disease, might contribute to the high prevalence of insulin resistance reported in patients with Parkinson's disease. We examined the effects of levodopa-carbidopa on glycogen concentration, glycogen synthase activity, and insulin-stimulated glucose transport in skeletal muscle, the predominant insulin-responsive tissue. In isolated muscle, levodopa-carbidopa completely prevented insulin-stimulated glycogen accumulation and glucose transport. The levodopa-carbidopa effects were blocked by propranolol, a β-adrenergic antagonist. Levodopa-carbidopa also inhibited the insulin-stimulated increase in glycogen synthase activity, whereas propranolol attenuated this effect. Insulin-stimulated tyrosine phosphorylation of insulin receptor substrate (IRS)-1 was reduced by levodopa-carbidopa, although Akt phosphorylation was unaffected by levodopa-carbidopa. A single in vivo dose of levodopa-carbidopa increased skeletal muscle cAMP concentrations, diminished glycogen synthase activity, and reduced tyrosine phosphorylation of IRS-1. A separate set of rats was treated intragastrically twice daily for 4 wk with levodopa-carbidopa. After 4 wk of treatment, oral glucose tolerance was reduced in rats treated with drugs compared with control animals. Muscles from drug-treated rats contained at least 15% less glycogen and ∼50% lower glycogen synthase activity compared with muscles from control rats. The data demonstrate β-adrenergic-dependent inhibition of insulin action by levodopa-carbidopa and suggest that unrecognized insulin resistance may exist in chronically treated patients with Parkinson's disease.

Original languageEnglish (US)
Pages (from-to)2339-2346
Number of pages8
JournalJournal of Applied Physiology
Volume97
Issue number6
DOIs
StatePublished - Dec 2004
Externally publishedYes

Fingerprint

Glycogen Synthase
Glycogen
Skeletal Muscle
Insulin
Glucose
Parkinson Disease
Insulin Receptor Substrate Proteins
Phosphorylation
Propranolol
Muscles
Tyrosine
Insulin Resistance
levodopa drug combination carbidopa
Adrenergic Antagonists
Glucose Tolerance Test
Pharmaceutical Preparations
Adrenergic Agents

Keywords

  • Diabetes
  • Dopamine
  • Insulin resistance
  • Parkinson's disease

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Levodopa with carbidopa diminishes glycogen concentration, glycogen synthase activity, and insulin-stimulated glucose transport in rat skeletal muscle. / Smith, Jill L.; Ju, Jeong Sun; Saha, Bithika M.; Racette, Brad A.; Fisher, Jonathan S.

In: Journal of Applied Physiology, Vol. 97, No. 6, 12.2004, p. 2339-2346.

Research output: Contribution to journalArticle

Smith, Jill L. ; Ju, Jeong Sun ; Saha, Bithika M. ; Racette, Brad A. ; Fisher, Jonathan S. / Levodopa with carbidopa diminishes glycogen concentration, glycogen synthase activity, and insulin-stimulated glucose transport in rat skeletal muscle. In: Journal of Applied Physiology. 2004 ; Vol. 97, No. 6. pp. 2339-2346.
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