Role of the availability of substrates on hepatic and renal gluconeogenesis in the fasted late pregnant rat.

Studies were conducted to examine the role of gluconeogenetic substrate availability on glucose production in the fasted late pregnant rat. Virgin and 21-day pregnant rats were studied after 24 hours' food deprivation. Pregnant animals showed decreased circulating glucose and gluconeogenic amino acid and increased plasma glycerol concentration. Glucose formation was studied in vivo two, five, and ten minutes after the intravenous administration of two concentrations of 14C-alanine, 14C-pyruvate, or 14C-glycerol. Concentrations of 0.2 mmols of 14C-glycerol or 14C-pyruvate, but not of 14C-alanine, enhanced 14C-glucose production in pregnant rats, whereas 1 mmol of any of the three 14C-substrates always enhanced 14C-glucose production in these rats. Both 1 mmol/L and 5 mmol/L 14C-alanine increased 14C-glucose formation in 90-minute-incubated liver slices of fasted pregnant rats, in spite of decreased cytosolic activity of alanine aminotransferase. The three substrates enhanced "in vitro" renal gluconeogenesis in pregnant rats. Under all experimental conditions studied, labeled glycerol was converted more efficiently into glucose than equivalent amounts of any other substrate used, and this difference was greater in pregnant, than in virgin animals. Results indicate that, in spite of enhanced gluconeogenetic activity, maternal glucose production in the fasted state at late gestation is limited by the deficiency of certain substrates, such as amino acids. It is proposed that glycerol derived from enhanced maternal adipose tissue lipolysis constitutes a preferential gluconeogenetic substrate in comparison with others, such as alanine, that are more efficiently transferred through the placenta to the fetus.