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 mumol.min-1.g liver-1) compared with low-protein animals (from 0.53 +/- 0.11 to 2.05 +/- 0.24 mumol.min-1.g liver-1). Insulin (1 nM) decreased (P < 0.001) HGO in controls to 2.39 +/- 0.37 mumol.min-1.g liver-1 after 10 min but increased HGO (to 2.82 +/- 0.40 mumol.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 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.
Ozanne
S E
SE
Department of Clinical Biochemistry, University of Cambridge, Addenbrooke's Hospital, United Kingdom.
Smith
G D
GD
Tikerpae
J
J
Hales
C N
CN
D000818:Animals; D000831:Animals, Newborn; D005260:Female; D005934:Glucagon / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D051273:Glucose Transporter Type 2; D007328:Insulin / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism; D007774:Lactation; D008099:Liver / Q000378:metabolism*; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D011247:Pregnancy; D011248:Pregnancy Complications; D011270:Pregnancy, Animal / Q000378:metabolism*; D011488:Protein Deficiency / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D051273:Glucose Transporter Type 2; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D005934:Glucagon; D005947:Glucose