Increased insulin action in the rat after protein malnutrition early in life

The effect of a limited period of low protein feeding in young rats on insulin secretion and insulin action during adult-age has been studied. Four-week-old rats were maintained for 4 weeks on isocaloric diets containing 5% protein (low protein) or 15% protein (control). The low protein rats gained weight at a considerably lower rate than the control rats. This was obtained in the absence of any decrease of spontaneous food intake. Basal plasma insulin levels were decreased (p less than 0.01) by 40% in low protein rats. However, the glucose-stimulated insulin secretion obtained in vivo after an i.v. glucose load remained normal. The basal plasma glucose level in the low protein rats was only marginally decreased (by 20%). The tolerance to i.v. glucose was found to be slightly enhanced in the low protein rats as compared to the control rats as shown by a significantly increased K value (p less than 0.01). In vivo insulin action in the low protein rats was investigated using the euglycaemic-hyperinsulinaemic clamp technique in conjunction with isotopic measurements of glucose turnover. The overall glucose utilization rate was normal in the basal state but significantly increased (p less than 0.05) when measured at a submaximal plasma insulin level. The basal hepatic glucose production in the low protein rats was similar to that in the control rats. During the clamp studies, the suppression of endogenous glucose production was found to be similar in the low protein rats and the control rats but this was obtained at significantly lower (p less than 0.01) steady-state insulin levels in the low protein group than in the control group. In conclusion, the current results indicate that the modest improvement of glucose tolerance which is revealed in the low protein rats results from changes in the insulin action upon the target tissues: both the insulin-mediated glucose uptake by peripheral tissues and the ability of insulin to suppress hepatic glucose output are enhanced.