Fasting glucose homeostasis in the adaptation to chronic nutritional deprivation in rats.

The hormonal basis for the metabolic paradox of relative hypoglycemia despite insulinopenia and insulin resistance in chronic nutritional deprivation was studied in weanling rats restricted to 60% of ad libitum intake over 8 wk (n = 12 each). Lower insulin and glucagon levels were observed in both peripheral and portal blood (P = 0.0016) in the malnourished rats on multivariate analysis of variance, indicating decreased islet secretion. Peripheral and portal hormone levels were proportionately similar, indicating that hepatic extraction was not altered. Despite relative hypoglycemia, glucose turnover rate, total glucose mass, and volume of distribution of glucose were not altered. This indicates that the sum total of the effects of malnutrition on the various hormonal influences controlling glucose turnover had resulted in the establishment of a new dynamic equilibrium associated with lower plasma glucose levels. It is concluded that fasting glucose levels are sustained at a lower level in chronic malnutrition by an adaptive process that includes insulin resistance and insulinopenia, counterbalanced not only by glucagon resistance, as shown earlier, but also by decreased glucagon secretion.