Altered regulation of hepatic glucose output in the male offspring of protein-malnourished rat dams

Offspring of protein-malnourished rat dams have permanent alterations in hepatic enzyme activities associated with glucose homeostasis. Hormonal control of hepatic glucose output (HGO) was studied in male offspring of dams fed either a 20% (control) or 8% (low protein) protein diet during pregnancy and lactation. Glucagon (210 pM) stimulated HGO significantly more (P < 0.04) in controls (from 0.72 +/- 0.11 to 3.18 +/- 0.30 mu mol . min(-1). g liver(-1)) compared with low-protein animals (from 0.53 +/- 0.11 to 2.05 +/- 0.24 mu mol . min(-1). g liver(-1)). Insulin (1 nM) decreased (P < 0.001) HGO in controls to 2.39 +/- 0.37 mu mol . min(-1). g liver(-1) after 10 min but increased HGO (to 2.82 +/- 0.40 mu mol . min(-1). g liver(-1); P < 0.04) in low-protein rats. There were fivefold fewer (P = 0.01) glucagon receptors but a threefold increase (P < 0.05) in hepatic insulin receptor number in the low-protein rats, which was reflected by increased insulin uptake (P < 0.07) and a threefold increase in insulin degradation (P < 0.001). The glucose transporter GLUT-2 was also raised threefold in the low-protein group (P < 0.001). The anomalous response to insulin indicates changes in its metabolic signaling, but normal insulin binding suggests that this alteration is a postreceptor event.