Glucose Turnover and Hepatocyte Glucose Production of Starved and Toxaemic Pregnant Sheep

Abstract

Ewes bearing twins were starved for 10 days during the last month of gestation to induce ovine pregnancy toxaemia (OPT). Glucose turnover was measl,lred by a primed continuous infusion of [U_ '4C]_ and [6-3HJglucose at the end of 10 days of starvation (non-susceptible), or earlier when ewes became recumbent with OPT (susceptible). All ewes were slaughtered at the end of the infusion and hepatocytes were prepared in order to measure glucose production from different substrates. Many of the ewes had dead foetuses when slaughtered. Glucose production rates by hepatocytes with the substrates propionate, lactate or alanine were significantly less from the susceptible ewes than were those from non-susceptible ewes. These low rates were not stimulated by incubation with glucagon (10-8 M), glutamine or glycerol. Rates of glucose turnover and of hepatic glucose production from all substrates were higher for ewes with dead than with live foetuses. The data support the hypothesis that pathogenesis of OPT is related to an impairment of hepatic gluconeogenesis, and further suggest that, in starved pregnant ewes, maternal glucose production may be restrained in the presence of a live foetus.