Alteration of the counterregulatory hormones in the conscious rat after protein-energy restriction.

We have recently reported that in rats submitted to protein-energy restriction early in life, an increased insulin efficiency upon the whole-body glucose utilization rate may be one reason for their chronic mild basal hypoglycaemia. However, the basis for their low plasma glucose level may also lie in the impaired activation of one or several of the counterregulatory hormones that prevent or correct hypoglycaemia. Our study was therefore designed to compare glucose counterregulatory mechanisms in restricted and control rats, both in the basal postabsorptive state and at controlled high plasma insulin level and standardized low glycaemic level (hypoglycaemic-hyperinsulinaemic glucose clamps performed in conscious rats). When tested in the basal postabsorptive state, the restricted rats exhibited prominent increases in the plasma levels of epinephrine (4.5 fold), norepinephrine (3.4 fold) and glucagon (1.7 fold). This was in the presence of significant decreases of plasma growth hormone and corticosterone levels (by 59 and 32%, respectively). With respect to the responses to acute severe hypoglycaemia (2.5 mmol/l), the glucagon, epinephrine and norepinephrine plasma levels in the restricted rats increased to values similar to those in controls. Also, the corticosterone level increased but remained significantly lower (p < 0.001) compared to the control response. The plasma growth hormone level was not significantly affected by acute hypoglycaemia in the restricted or in the control groups. We conclude that protein-energy restriction, starting early in life in the rat, severely impairs the release of counterregulatory hormones that defend against hypoglycaemia.