1: J Appl Physiol. 2004 Dec;97(6):2339-46. Epub 2004 Jul 16.

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

Smith JL, Ju JS, Saha BM, Racette BA, Fisher JS.

Dept. of Biology, St. Louis University, 3507 Laclede Ave., St. Louis, MO 63103,
USA. smithjl@slu.edu

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 beta-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 approximately 50% lower glycogen synthase activity compared with
muscles from control rats. The data demonstrate beta-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.


PMID: 15258132 [PubMed - indexed for MEDLINE]