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Developmental regulation of glucogenesis in the sheep fetus during late gestation - PubMed

  • ️Thu Jan 01 1998

Developmental regulation of glucogenesis in the sheep fetus during late gestation

A L Fowden et al. J Physiol. 1998.

Abstract

1. Using tracer methodology, endogenous glucose production was measured in twenty-six chronically catheterized sheep fetuses during normal fed conditions and in response to a 48 h period of maternal fasting at different gestational ages during the last 10-15 days of gestation (term, 145 +/- 2 days). 2. In normal fed conditions, the rate of fetal glucose production was negligible until 143-145 days when it rose significantly to account for 50 % of the glucose used by the fetus. The rise in fetal glucogenesis towards term closely parallelled the normal prepartum rise in fetal plasma cortisol and catecholamines. 3. Maternal fasting for 48 h induced endogenous glucose production in fetuses at 139-141 days but not at 133-135 days of gestation. Maternal fasting also induced increases in the plasma cortisol and noradrenaline levels in all the fetuses studied. Fetal plasma cortisol levels at the end of the fast and the increment in fetal plasma cortisol during maternal fasting were significantly greater in the older groups of fasted animals. 4. When the data from all the fetuses were combined, partial correlation analysis of fetal glucose production and the log plasma concentrations of cortisol and total catecholamines showed that plasma cortisol was the predominant regulator of fetal glucogenesis during late gestation. However, once plasma cortisol levels exceeded 17.5 ng ml-1, plasma catecholamines were a major influence on fetal glucogenesis. 5. The results show that glucogenesis occurs in fetal sheep during late gestation in conditions in which the fetal plasma concentrations of cortisol and catecholamines are elevated. They also suggest that cortisol enhances the capacity for glucogenesis in utero, while catecholamines actually activate glucose production in sheep fetuses close to term.

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Figures

Figure 1
Figure 1. Gestational trend in fetal glucose production

Mean (±

s.e.m.

) values of endogenous glucose production (▴), plasma cortisol (▾), plasma adrenaline (○), plasma noradrenaline (formula image) and total plasma catecholamines (•) and of hepatic glycogen (▪) and glucose-6-phosphatase (G6P; □) in sheep fetuses with respect to gestational age. Data are plotted at the mean gestational age for each age group. n = 4–6 at each age. Values with different letters are significantly different from each other: P < 0.05 (ANOVA). † Data from Fowden et al. 1993. *P < 0.01 (paired t test): significant rate of glucose production.

Figure 2
Figure 2. Fetal glucose metabolic rates in response to maternal fasting

Mean (±

s.e.m.

) rates of umbilical glucose uptake (A), glucose utilization (B), glucose production (C{kern 0 0}) and CO2 production from glucose carbon (D) in sheep fetuses in both the fed (□) and fasted (formula image) state and the mean change in value (formula image) during the 48 h period of maternal fasting in Group I (fed 130–132 days, fasted 133–135 days) and Group II (fed 136–138 days, fasted 139–141 days). *P < 0.05; **P < 0.01: significant change in value during fasting. †P < 0.05: significant rate of Sera glucose production.

Figure 3
Figure 3. Fetal glucose production and plasma cortisol

The relationship between the rate of endogenous glucose production and the plasma cortisol concentration in individual sheep fetuses in fed (•) and fasted states (○) during late gestation (y = 15.4log10x - 14.6, r = 0.712, n = 36, P < 0.001).

Figure 4
Figure 4. Fetal glucose production and plasma catecholamines

The relationship between the rate of endogenous glucose production and the total plasma catecholamine concentration in individual sheep fetuses in fed (•) and fasted states (○) with plasma cortisol levels less than 17.5 ng ml−1 (y = 2.0log10x - 4.8, r = 0.176, n = 17, P > 0.05) (A) and greater than 17.5 ng ml−1 (y = 18.0 log10x - 38.8, r = 0.737, n = 15, P < 0.001) (B).

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References

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