Altered regulation of hepatic glucose output in the male offspring
of protein malnourished rat dams.
Ozanne, S. E., G. D. Smith, J. Tikerpae & C. N. Hales.
University of Cambridge, Department of Clinical Biochemistry,
Addenbrooke's Hospital, Hills Road, Cambridge, CB2 2QR, U.K.
APStracts 2:0246E, 1995.
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/g liver) compared to low
protein animals (from 0.53 +/- 0.11 to 2.05 +/- 0.24 [mu]mol/min/g
liver). Insulin (1 nM) decreased (p < 0.001) HGO in controls to
2.39 +/- 0.37 [mu]mol/min/g liver after 10 min but increased HGO ( to
2.82 +/- 0.40 [mu]mol/min/g liver) (p < 0.04) in low protein
rats. There were 5-fold fewer (p = 0.01) glucagon receptors but a 3
-fold 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 3 -fold increase in insulin degradation (p
< 0.001). The glucose transporter Glut 2 was also raised 3 fold
in the low protein group (p < 0.001). The anomalous response to
insulin indicates changes in its metabolic signalling but normal
insulin binding suggests that this alteration is a post-receptor
event.
Received 15 August 1995; accepted in final form 21 November 1995.
APS Manuscript Number E392-5.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 8 December 95