Metabolic and endothelial effects of trimetazidine on forearm skeletal muscle in patients with type 2 diabetes and ischemic cardiomyopathy.
The aim of the present study was to evaluate the effect of prolonged inhibition of beta-oxidation on glucose and lipid muscle forearm metabolism and cGMP and endothelin-1 forearm release in patients with type 2 diabetes mellitus and ischemic cardiomyopathy. Fifteen patients were randomly allocated in a double-blind cross-over parallel study with trimetazidine (20 mg tid) or placebo lasting 15 days. At the end of each period, all patients underwent euglycemic hyperinsulinemic clamps with forearm indirect calorimetry and endothelial balance of vasodilator and vasoconstricor factors. Compared with placebo, trimetazidine induced 1) an increase in insulin-induced forearm glucose uptake and glucose oxidation accompanied by a reduction in forearm lipid oxidation and citrate release and 2) a decrease of endothelin-1 release paralleled by a significant increase in forearm cGMP release. Forearm glucose oxidation significantly correlated with cGMP release (r=0.37, P<0.04), whereas forearm lipid oxidation positively correlated with endothelin-1 release (r=0.40, P<0.03). In conclusion, for the first time, we demonstrated that insulin-induced forearm glucose oxidation and forearm cGMP release were increased whereas forearm endothelin-1 release was decreased during trimetazidine treatment. Muscle's metabolic and vascular effects of trimetazidine add new interest in the use of trimetazidine in type 2 diabetic patients with cardiovascular disease.
Monti
Lucilla D
LD
Laboratory L20, Core Lab., Diabetology, Endocrinology and Metabolic Disease Unit, IRCCS H San Raffaele, Via Olgettina 60, 20132 Milan, Italy. monti.lucilla@hsr.it
Setola
Emanuela
E
Fragasso
Gabriele
G
Camisasca
Riccardo P
RP
Lucotti
Pietro
P
Galluccio
Elena
E
Origgi
Anna
A
Margonato
Alberto
A
Piatti
PierMarco
P
D020155:3-Hydroxybutyric Acid / Q000378:metabolism; D000368:Aged; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D019343:Citric Acid / Q000378:metabolism; D018592:Cross-Over Studies; D006152:Cyclic GMP / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000378:metabolism*; D004311:Double-Blind Method; D019332:Endothelin-1 / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005542:Forearm / Q000098:blood supply; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000097:blood / Q000150:complications / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D014292:Trimetazidine / Q000494:pharmacology*
D001786:Blood Glucose; D019332:Endothelin-1; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D019343:Citric Acid; D006152:Cyclic GMP; D005947:Glucose; D014292:Trimetazidine; D020155:3-Hydroxybutyric Acid