title: More marked stimulation by lithium than insulin of the glycogenic pathway in rat skeletal muscle.
abstract: Lithium's impact on glucose metabolism was compared with that of insulin in isolated rat soleus muscle. Lithium chloride (20 mmol/l) induced a 4.8-fold more pronounced increment over basal glycogen synthase activity than insulin (10 nmol/l) (nmol UDP-glucose into glycogen in synthase activity assay.g-1.min-1: lithium, +22.1 +/- 1.8 vs. insulin, +4.6 +/- 3.9; P < 0.01). In parallel, lithium was less efficient than insulin in stimulating glucose transport (counts per minute 2-deoxy-D-[3H]glucose.mg-1.h-1: lithium, +211 +/- 19 vs. insulin, +311 +/- 57; P < 0.05) and lactate release (mumol.g-1.h-1: lithium, +1.0 +/- 0.5 vs. insulin, +3.9 +/- 0.5; P < 0.01), and similar increments were induced in glycogen synthesis (mumol glucose into glycogen.g-1.h-1: lithium, +3.32 +/- 0.43 vs. insulin, +3.46 +/- 0.47; not significant). Full additivity of glycogenic effects and divergent dependency on phosphatidylinositol 3-kinase activation provided further evidence for different mechanisms of action. In muscle from insulin-resistant obese Zucker rats (fa/fa), failure of lithium to reverse deficits in glucose metabolism suggested a primary deficit in muscle glucose uptake rather than glycogen synthesis. Hence lithium distinctly stimulates glycogen synthase activity in skeletal muscle and may therefore be regarded as a candidate for the treatment of disorders associated with primary deficits in the glycogenic pathway.
authors.affiliation: Department of Medicine III, University of Vienna, Austria.
authors.forename: C
authors.initials: C
authors.lastname: Fürnsinn
authors.forename: C
authors.initials: C
authors.lastname: Noe
authors.forename: R
authors.initials: R
authors.lastname: Herdlicka
authors.forename: M
authors.initials: M
authors.lastname: Roden
authors.forename: P
authors.initials: P
authors.lastname: Nowotny
authors.forename: B
authors.initials: B
authors.lastname: Leighton
authors.forename: W
authors.initials: W
authors.lastname: Waldhäusl
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D003571:Cytochalasin B / Q000494:pharmacology; D003620:Dantrolene / Q000494:pharmacology; D003847:Deoxyglucose / Q000378:metabolism; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D006003:Glycogen / Q000378:metabolism*; D006006:Glycogen Synthase / Q000378:metabolism*; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D007773:Lactates / Q000378:metabolism; D018021:Lithium Chloride / Q000494:pharmacology*; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D009765:Obesity / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011924:Rats, Zucker; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D007328:Insulin; D007773:Lactates; D003571:Cytochalasin B; D007334:Insulin-Like Growth Factor I; D006003:Glycogen; D003847:Deoxyglucose; D006006:Glycogen Synthase; D003620:Dantrolene; D018021:Lithium Chloride; D005947:Glucose; D007545:Isoproterenol; D000077191:Wortmannin