Protein-energy malnutrition induces changes in insulin sensitivity

Early protein deprivation impairs glucose tolerance and insulin secretion, but the former generally recovers first. We have therefore investigated insulin sensitivity in vivo and in isolated muscle and cultured hepatocytes during protein-energy malnutrition and long-term follow-up in rats. Rats were weaned at 3 weeks onto normal rat chow (N rats) or onto 5% protein diet (LP rats). At 6 w of age LP rats were transferred to N chow. Insulin sensitivity was studied in the three systems at 3, 6, 12 and 24 w. At 6 w LP rats showed a greater and more prolonged fall in serum glucose in response to injected insulin than age--or weight--matched N, but by 12 w the difference was not significant. Similarly, soleus muscle from 6 w LP showed a higher basal rate of glucose transport and responded to a lower insulin dose than N, but there was no difference in sensitivity at 12 w. Hepatocytes from 6 w LP showed higher basal incorporation of glucose into glycogen than N, but insulin sensitivity was not different. Thymidine incorporation into hepatocyte DNA responded to lower insulin doses in 6 w LP than N. There was a decrease in insulin sensitivity with age in all experimental systems. Increased insulin sensitivity during malnutrition was seen in all tissues studied but differences between the two groups were not significant at 12 w and probably do not account for the normal glucose tolerance in the presence of low serum insulin levels previously reported.