Severe diabetes inhibits resistance exercise-induced increase in eukaryotic initiation factor 2B activity

Rates of protein synthesis are reduced in severely diabetic rats. A potenti al mechanism through which insulin can stimulate protein synthesis is modul ation of the activity of eukaryotic initiation factor 2B (eIF2B). The activ ity of this factor is elevated after exercise in nondiabetic rats but is ma rkedly lower in skeletal muscle from nonexercised severely diabetic rats. W e tested the hypothesis that a failure to increase eIF2B activity after exe rcise is one potential reason for a failure of severely diabetic rats to in crease rates of protein synthesis after resistance exercise. Diabetic (part ial pancreatectomy, plasma glucose >475 mg/dl) and nondiabetic male Sprague -Dawley rats (similar to 300 g) performed acute moderate-intensity resistan ce exercise or remained sedentary. Rates of protein synthesis were higher i n nondiabetic rats and increased significantly with exercise, while no elev ation was found in severely diabetic rats. The activity of eIF2B was higher (P < 0.05) in exercised nondiabetic than in sedentary nondiabetic rats (0. 096 <plus/minus> 0.016 and 0.064 +/- 0.02 pmol GDP exchanged/min, respectiv ely), but no difference was observed between sedentary and exercised diabet ic rats (0.037 +/- 0.001 and 0.044 +/- 0.008 pmol GDP exchanged/min, respec tively), and these activities were lower (P, 0.05) than in nondiabetic anim als. These data suggest that severe hypoinsulinemia is associated with an i nability to increase eIF2B activity in response to exercise.