Neonatal Hypoglycaemia

Shelley, Heather J.; Neligan, G. A.

doi:10.1093/oxfordjournals.bmb.a070433

Cited by 226 publications

(101 citation statements)

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“…Galactose is thus abundant throughout infancy and, in particular, during the immediate postnatal period (25) when glycogen levels and blood glucose concentrations are lowest. If liver glycogen plays an important role in acute glucose homeostasis in the newborn (25), then it follows from our speculation that galactose may be secondarily important by ensuring glycogen stores (Fig. 6) adequate to maintain normoglycemia.…”

Section: Discussionmentioning

confidence: 99%

Glycogen Regulation in Isolated Perfused Near Term Monkey Liver

et al. 1976

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ExtractGlycogen metabolism was studied in the isolated perfused liver of the monkey conceptus at 90% of gestation using an in situ recirculating perfusion system. Net uptake of glucose and galactose and the activities of the enzymes, glycogen synthetase and phosphorylase, were studied in response to varied perfusate composition. Synthetase activity was expressed as %I, the percentage of total synthetase activity in the active form. Perfusate glucose concentrations a s high as 700 mg/ 100 ml did not lead to net glucose uptake or to an increase in the baseline %I synthetase ( 4 1, mean & SEM). In the presence of 300 mg/100 ml glucose, insulin a t M increased %I to 8 i 2, and galactose > 75 mg/100 ml increased %I to 8 & 1. The combination of galactose, glucose, and insulin increased %I to 40 A 5. With this latter combination, synthetase activity was proportional to perfusate glucose concentration above 100 mg/100 ml. Phosphorylase activity was diminished by either galactose or insulin, and phosphorylase activity was lowest in the group receiving galactose, glucose, and insulin. Galactose was taken up by all livers, but net glucose uptake was not observed under any condition; net hexose uptake was observed in perfusions with galactose. Glycogen levels did not vary significantly with varied perfusate composition during the 30-min perfusion periods. Speculation W e speculate that galactose may be uniquely important for neonatal liver glycogen synthesis, and that its action is mediated through reciprocal changes in the activities of the enzymes, glycogen synthetase and phosphorylase. If liver glycogen is important for acute neonatal glucose homeostasis, then galactose may also be essential for maintaining circulating glucose concentration by ensuring glycogen synthesis during feeding.

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Section: Discussionmentioning

confidence: 99%

Glycogen Regulation in Isolated Perfused Near Term Monkey Liver

et al. 1976

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“…Evidence has accumulated in recent years to show that the control of carbohydrate metabolism in the young animal, during the period between birth and weaning, differs from that in the adult in a variety of ways (Shelley, 1961(Shelley, , 1969Edwards, 1966Edwards, , 1970van Duyne, 1966) and the situation is further complicated by wide differences between species (Shelley & Neligan, 1966). In the calf, removal of either the pituitary or of both adrenal glands results in death from hypoglycaemia within 24 hr in the absence of adequate replacement therapy (Comline & Edwards, 1965), whereas adult animals develop an increased sensitivity to the hypoglycaemic effect of insulin over a period of several weeks under these conditions but do not become hypoglycaemic spontaneously unless food is witheld (de Bodo & Altszuler, 1958).…”

Section: Responses To Stimulation Of Both Splanchnic Nervesmentioning

confidence: 99%

The glycogenolytic response to stimulation of the splanchnic nerves in adrenalectomized calves, sheep, dogs, cats and pigs

Edwards¹

1971

The Journal of Physiology

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SUMMARY1. The effects of stimulation of the peripheral ends of one or both splanchnic nerves have been investigated in calves, sheep, dogs, cats and pigs after removal of both adrenal glands.2. Stimulation of both splanchnic nerves produced comparable hyperglycaemic and glycogenolytic effects in sheep, dogs and cats; the mean liver glycogen concentration was reduced by between 7 0 and 10O5 mg/g, five min after stimulation was discontinued, at which time the mean plasma glucose concentration had risen by between 126 and 137 mg/100 ml.3. In five 3-5 week-old calves which were tested under identical conditions the mean liver glycogen concentration was reduced by 13.3 + 1.9 mg/g and the plasma glucose concentration raised by 216 + 1-9 mg/100 ml., 5 min after stimulation was terminated.4. In pigs, stimulation of both splanchnic nerves invariably produced a rise in the plasma glucose concentration, even when the concentration of glycogen in the liver was less than 5 mg/g before stimulation. The response was, nevertheless, considerably smaller in these animals than in any of the other species investigated.5. Splanchnic nerve stimulation also caused a rise in mean aortic blood pressure and blood haematocrit during the period of stimulation; changes of approximately the same order of magnitude were encountered in all five species.6. Dogs were found to resemble calves in that the hyperglycaemic response to stimulation of a single splanchnic nerve did not differ significantly from that obtained when both were stimulated simultaneously; furthermore, either nerve was found to be equally effective.7. In cats the change in plasma glucose concentration in response to stimulation of a single splanchnic nerve was always less than that which occurred in response to bilateral stimulation although comparable changes in blood haematocrit occurred in both groups of animals.8. It is concluded that stimulation of the splanchnic nerves causes break-down of glycogen in the livers of various unrelated species of adult animals but that the magnitude of the hyperglyeaemic response in the young calf provides further evidence of the importance of the sympathetic system in the control of metabolism in the young animal.

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“…This high risk of hypoglycemia may be related to small substrate stores, a high brain-to-body weight ratio, and immature enzyme systems (4 -6), thereby disturbing the balance between glucose supply and requirements. Limited endogenous glucose production is attributed to restricted capacity for gluconeogenesis and glycogenolysis (4,(33)(34)(35)(36)(37)(38)(39)(40). However, direct measurements of glucose production and glucose concentration were done mostly without or during a constant glucose infusion rate (6 -9, 11, 13, 15, 16), precluding conclusions about the adaptive capacity.…”

Section: Discussionmentioning

confidence: 99%

Adaptation of Glucose Production and Gluconeogenesis to Diminishing Glucose Infusion in Preterm Infants at Varying Gestational Ages

et al. 2003

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In preterm infants low plasma glucose concentrations are frequently observed. We hypothesized that the infants' ability to adapt endogenous glucose production to diminishing exogenous supply is disturbed, but will improve with increasing gestational age. Glucose production rate and gluconeogenesis were measured using stable isotope techniques with [6,6-2 H 2 ]glucose and [2-13 C]glycerol in 19 preterm infants (10 Յ 30 wk and nine Ͼ30 wk gestational age) on d 5.0 Ϯ 1.4 of life. Exogenous glucose was administered at a rate of 33 mol·kg Ϫ1 ·min Ϫ1 followed by 22 mol·kg Ϫ1 ·min Ϫ1 . In the first 2 h after the decrease in exogenous supply, plasma glucose concentration declined comparably in both groups: Յ30 wk, from 4.3 Ϯ 1.2 to 3.2 Ϯ 0.9 mM; Ͼ30 wk, from 3.7 Ϯ 0.7 to 3.0 Ϯ 0.6 mM. Thereafter, only in infants Ͼ30 wk an increase was observed, to 3.4 Ϯ 0.8 mM. Glucose production rate increased comparably in both groups: Յ30 wk, from 6.0 Ϯ 4.1 to 8.8 Ϯ 3.4 mol·kg Ϫ1 ·min Ϫ1 ; Ͼ30 wk, from 7.8 Ϯ 4.6 to 11.6 Ϯ 5.2 mol·kg Ϫ1 ·min Ϫ1 . This increase was equivalent to approximately 30% of the decline in exogenous glucose. Gluconeogenesis increased comparably in both groups: Ͻ30 wk, from 3.2 Ϯ 1.2 to 4.5 Ϯ 1.3 mol·kg Ϫ1 ·min Ϫ1 ; Ͼ30 wk, from 4.3 Ϯ 1.9 to 6.8 Ϯ 2.9 mol·kg Ϫ1 ·min Ϫ1 . We conclude that preterm infants can only partly compensate a decline in exogenous glucose supply by increasing endogenous glucose production rate, probably because of limitations in the final common pathway of intracellular glucose metabolism (i.e. glucose-6-phosphatase). The ability to maintain the plasma glucose concentration after a decrease in exogenous supply is better preserved in infants Ͼ30 wk owing to more efficient adaptation of peripheral glucose utilization. Abbreviations AGA, appropriate for gestational age CI, confidence interval GPR, (endogenous) glucose production rate MIDA, mass isotopomer distribution analysis Ra, rate of appearance SGA, small for gestational age A low plasma glucose concentration is frequently found in preterm infants, particularly during the first postnatal days, and may lead to serious short-term and long-term complications. The incidence is inversely related to declining gestational age and birth weight (1-3). Therefore, preterm infants routinely receive enteral feedings or i.v. glucose shortly after birth. Despite this policy, the incidence of hypoglycemia-defined as a plasma glucose concentration Ͻ 2.6 mM-is still approximately 20% in our neonatal intensive care unit, a referral unit for infants Յ 32 wk gestational age. The high risk of hypoglycemia may be related to limited substrate stores, a high brain-to-body weight ratio, and immature enzyme systems (4 -6).The pathophysiology of low plasma glucose concentrations in otherwise healthy preterm infants is not completely understood because of lack of sufficient data on glucose kinetics. Endogenous GPR in preterm infants of various gestational ages was measured under different circumstances (6 -18). In most studies glucose was supplied at varying rates, s...

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Neonatal Hypoglycaemia

Cited by 226 publications

References 0 publications

Glycogen Regulation in Isolated Perfused Near Term Monkey Liver

Glycogen Regulation in Isolated Perfused Near Term Monkey Liver

The glycogenolytic response to stimulation of the splanchnic nerves in adrenalectomized calves, sheep, dogs, cats and pigs

Adaptation of Glucose Production and Gluconeogenesis to Diminishing Glucose Infusion in Preterm Infants at Varying Gestational Ages

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