ALTERED REGULATION OF HEPATIC GLUCOSE OUTPUT IN THE MALE OFFSPRING OFPROTEIN-MALNOURISHED RAT DAMS

Offspring of protein-malnourished rat dams have permanent alterations in hepatic enzyme activities associated with glucose homeostasis. Horm onal control of hepatic glucose output (HGO) was studied in male offsp ring of dams fed either a 20% (control) or 8% (low protein) protein di et during pregnancy and lactation. Glucagon (210 pM) stimulated HGO si gnificantly 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 animal s (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 threef old increase (P < 0.05) in hepatic insulin receptor number in the low- protein rats, which was reflected by increased insulin uptake (P < 0.0 7) and a threefold increase in insulin degradation (P < 0.001). The gl ucose 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.