Release of glucose from the liver of fetal and postnatal sheep by portal vein infusion of catecholamines or glucagon.

Abstract

SUMMARY1. The blood flow to the liver in fetuses near term, newborn and adult sheep was measured by the Fick principle, using radionuclide-labelled plastic microspheres, before and during infusion of adrenaline, noradrenaline or glucagon.2. Glucose output and lactate consumption by the liver in sheep of each age group were calculated by application of the Fick principle using the concentration gradients of these metabolites measured in blood samples obtained, simultaneously with blood flow measurements, from catheters chronically implanted in the inflow and outflow vessels of the liver.3. Catecholamines were infused into the portal vein of fetuses near term at a rate comparable with that at which they are known to be secreted in the sheep fetus during moderate to severe hypoxia. The cardiovascular and metabolic responses to these infusions were found to be comparable with those that occur in the fetus during hypoxia.4. Catecholamines increased glucose output from the liver in all except the immediate post-partum animals. Catecholamines were less effective than glucagon in promoting glucose release. The mean increments in glucose output during adrenaline infusion were 0055+0-015 mmol min-(100 g liver)-1 in the fetus, 0-122+ 0024 mmol min-(100 g)-1 in the 2-week-old lambs, 0078+0019 mmol min-' (100 g)-' in young lambs and 0-049+0-012 mmol min-' (100 g)-' in the adult sheep.During glucagon infusion the mean glucose output increments were 0-146 + 0023 mmol min-1 (100 g)-in the fetus, 0-274+0-085 mmol min-(100 g)-1 in the 2-week-old and young lambs and 0 180+0-054 mmol min-' (100 g)-1 in the adult. Adrenaline was more potent than noradrenaline, suggesting that the major glycogenolytic response might be f-receptor mediated.5. In the immediate newborn period the output of glucose from the liver was high (0-20 + 0-05 mmol min-' (100 g liver)-' and was not statistically significantly increased by infusion either of glucagon or of catecholamines which resulted in similar increments of glucose output of about 04128 +0-133 mmol min-' (100 g)-1. It is probable that the high output of glucose reflected the high endogenous circulating levels of catecholamines and glucagon in these animals at birth and that further infusions failed to add significantly to the already near-maximal glucose release. R. S. K. APATU AND R. J. BARNES absence of high levels of circulating catecholamines and glucagon in the resting fetus but also may indicate a deficiency in either the receptor mechanism for catecholamines or of the intracellular second messenger system for glycogenolysis. The greater effectiveness of glucagon (than adrenaline) as a mediator of glucose release in these animals tends to support the idea of a fl-receptor rather than a second messenger deficiency. It is postulated that a deficiency of hepatic ,-adrenergic receptors, provided that it can be corrected in time for birth, would help to protect glycogen stores in the liver in utero.

Effects of colostrum versus formula feeding on hepatic glucocorticoid and α1- and β2-adrenergic receptors in neonatal calves and their effect on glucose and lipid metabolism

“…The trend for greater B max of α 1 -AR in colostrum-fed calves might be in accordance with the increasing importance of α 1 -AR for mediating sympathetic regulation of hepatic energy metabolism in the neonate, as seen for rats (Schmelck and Hanoune, 1980;Morgan et al, 1983;Huff et al, 1991), but correlations of α 1 -AR with parameters of hepatic energy metabolism (e.g., eGP) were barely detectable in our study. Both α 1 -and β 2 -AR are involved in hepatic regulation of eGP (Schmelck and Hanoune, 1980;Goodhardt et al, 1984;Apatu and Barnes, 1991) and probably also in regulation of FA oxidation (Schulze et al, 1986). However, different diets did not affect eGP on d 3 of life in our calves (Steinhoff-Wagner et al, 2011a) and no correlations of α 1 -AR binding density and eGP could be observed.…”

“…Glucocorticoids (Pilkis and Granner, 1992;Edgerton et al, 2006) and the adrenergic system (Goodhardt et al, 1984;Apatu and Barnes, 1991;Fowden and Forhead, 2011) stimulate eGP and may also affect FA oxidation (Olubadewo and Heimberg, 1993;Lettéron et al, 1997) and triacylglyceride storage in liver (Vegiopoulos and Herzig, 2007;Rose et al, 2010). In calves, β-adrenergic agonists stimulated glycogenolysis and fat mobilization in a dose-dependent manner (Blum and Flueckiger, 1988), whereas treatment with dexamethasone, a potent glucocorticoid, failed to stimulate postnatal eGP, but provoked peripheral insulin resistance Scheuer et al, 2006).…”

“…Catecholamines and the adrenergic system play a pivotal role in perinatal maturation of metabolic processes in the liver related to energy supply (e.g., eGP; Apatu and Barnes, 1991;Fowden and Forhead, 2011) and FA oxidation (Olubadewo and Heimberg, 1993) in neonates, including calves (Hammon et al, 2012(Hammon et al, , 2013. Plasma concentrations of adrenaline and noradrenaline are elevated around birth and support metabolic adaptation for postnatal life (Eliot et al, 1981;Richet et al, 1985;Hume et al, 2005).…”

Effects of protein-free energy supplementation on blood metabolites, insulin and hepatic PEPCK gene expression in growing lambs offered rice straw-based diet

“…It was not surprising that the blood glucose concentration tended to increase with supplementing cornstarch, but the differences between treatments were not significant, indicating that there exist mechanisms to regulate the blood glucose concentration within a normal physiological range (Devaskar et al, 1984;Apatu and Barnes, 1991). Serum insulin is highly sensitive to blood glucose, and was increased by supplemental cornstarch in the present study (Figure 1).…”

Pancreatic α Cell Function in the Fetal Foal During Late Gestation

“…Glucagon is present in fetal plasma of a number of species and its concentration is elevated during stressful conditions, such as hypoxia and anaesthesia, which lead to glucogenesis in utero (Alexander et al 1971;Chez et al 1974;Girard et al 1974;Shelley & Girard, 1981;Silver et al 1985). Glucagon has also been shown to induce hyperglycaemia and hepatic glucose production in fetuses close to term (Girard et al 1973;Devaskar et al 1984;Apatu & Barnes, 1991). However, relatively little is known about the developmental changes in fetal á cell function during the period of late gestation when the ability of the fetus to produce glucose endogenously normally rises (Fowden et al 1991;Fowden, 1997).…”