Effet de l'insuline sur le transport des acides aminés et la synthèse protéique dans le muscle squelettique de la souris normale et de la souris insulinorésistante

The uptake of alpha-aminoisobutyric acid (AIB) and protein synthesis were studied in soleus muscles isolated from lean and goldthioglucose-obese mice (GTG-obese mice) in both basal and insulin-stimulated conditions. Insulin stimulated AIB influx by increasing the apparent Vmax of transport; this effect was partially dependent on new protein synthesis. In muscles of GTG-obese mice, the basal (i.e. non-insulin-stimulated) influx of AIB was decreased. Furthermore, the effect of insulin in obese mice was altered in two ways; the absolute value of the maximally insulin-stimulated AIB influx was lower than in the muscles of lean controls, and the dose response of insulin-stimulated AIB influx was shifted to the right (half-maximally effective concentration: EC50 approximately equal to 1.7 nM) compared to that observed in the muscles of lean animals (EC50 approximately equal to 0.7 nM). On the contrary, protein synthesis was similar in control and GTG-obese mice in both basal and insulin-stimulated conditions. It is concluded that in the muscles of obese mice a) amino acid transport per se is altered, b) the sensitivity of this process to the stimulatory effect of insulin is markedly diminished and c) protein synthesis is unchanged.