Peroxovanadates have full insulin-like effects on glycogen synthesis in normal and insulin-resistant skeletal muscle.
1. The insulin-like effects of orthovanadate (10 mM) and peroxides of vanadate (peroxovanadates, at 1 mM) on rates of lactate formation, glucose oxidation and glycogen synthesis were measured in incubated soleus-muscle preparations isolated from non-obese Wistar rats and lean (fa/?) or insulin-resistant obese Zucker (fa/fa) rats. 2. The stimulation of the rates of lactate formation and glucose oxidation by either orthovanadate or peroxovanadates was of similar magnitude to the stimulation by a maximally effective concentration of insulin (1000 microunits/ml). 3. Peroxovanadates, but not orthovanadate, maximally stimulated the rate of glycogen synthesis in incubated soleus muscles isolated from Wistar rats. 4. When soleus-muscle preparations were incubated in the presence of both insulin (1000 microunits/ml) and peroxovanadates (1 mM), this did not result in a synergistic increase in the rate of total glucose utilization as compared with either agent alone. 5. Soleus muscles isolated from obese (fa/fa) Zucker rats exhibited a decrease in response to a physiologically relevant concentration of insulin (100 microunits/ml). Peroxovanadates, at 1 mM, maximally stimulated the rate of glycogen synthesis in soleus muscles isolated from obese (fa/fa) Zucker rats. 6. The findings indicate that peroxovanadates are useful and important agents for investigating the mechanism of action of insulin in skeletal muscle.
Leighton
B
B
Department of Biochemistry, University of Oxford, U.K.
Cooper
G J
GJ
DaCosta
C
C
Foot
E A
EA
D000818:Animals; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000096:biosynthesis*; D006019:Glycolysis / Q000187:drug effects; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance; D007773:Lactates / Q000378:metabolism; D008297:Male; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011924:Rats, Zucker; D014638:Vanadates / Q000494:pharmacology*
D007328:Insulin; D007773:Lactates; C069276:peroxovanadate; D014638:Vanadates; D006003:Glycogen; D005947:Glucose