Sources of Blood Glucose in the Rat Fetus

Bossi, E; Greenberg, Robert E.

doi:10.1203/00006450-197210000-00004

Cited by 36 publications

(11 citation statements)

References 11 publications

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“…The rapid diffusion of glucose across the placenta in humans and animals has been described before (31)(32)(33)(34) (22) and Bossi and Greenberg (23) showed that the fetal plasma glucose specific activity was always lower than the maternal plasma glucose specific activity. These data would suggest that a fetal glucose source, in addition to maternal glucose diffusing across the placenta, was contributing to the fetal plasma glucose.…”

Section: Discussionmentioning

confidence: 78%

Glucose Production in Pregnant Women at Term Gestation

Kalhan¹,

D'Angelo²,

Savin³

et al. 1979

J. Clin. Invest.

196

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A B S T R A C T The effects of pregnancy and diabetes on systemic glucose production rates and the sources of glucose for the human fetus in utero were evaluated in five normal, four gestationally diabetic, and one insulin-dependent diabetic subject undergoing elective caesarean section at term gestation. Five normal nonpregnant women were studied for comparison. Systemic glucose production rates were measured with stable tracer [1-13C]glucose according to the primeconstant rate infusion technique. Even though the plasma glucose concentration during normal pregnancy had declined as compared with the nonpregnant subjects (P < 0.0005), the systemic glucose production rate was 16% greater, a rate sufficient to provide the glucose requirement of the fetus at term gestation. The decline in glucose concentration could be the result of an increase in apparent volume of distribution of glucose. Systemic glucose production rates in wellcontrolled, gestationally diabetic subjects were similar to those in normal pregnant subjects (2.07±0.53 vs. 2.42±0.51 mg/kg-min). The sources of glucose for the human fetus at term gestation were evaluated by comparing (a) natural variation in 13C:12C ratio of plasma glucose and (b) enriched '3C:'2C ratio ofplasma glucose during [1-13C]glucose infusion in maternal and fetal blood at delivery in both normal and diabetic subjects. These data showed that the fetal glucose pool was in equilibrium with the maternal glucose pool in both normal and diabetic subjects, indicating that a brief A preliminary report of this work has been published as an abstract: Pediatr. Res. 1977.

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Section: Discussionmentioning

confidence: 78%

Glucose Production in Pregnant Women at Term Gestation

Kalhan¹,

D'Angelo²,

Savin³

et al. 1979

J. Clin. Invest.

196

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“…Hence, lipid mobilization might have been inhibited by maintaining the newborns at thermal neutrality. The decrease observed in blood glycerol starting 2 h after birth might be attributable in part to its conversion to glucose (63). The fall in blood P-hydroxybutyrate with no change in acetoacetate cannot be explained by the data available.…”

Section: Methodsmentioning

confidence: 73%

Fuels, Hormones, and Liver Metabolism at Term and during the Early Postnatal Period in the Rat

Girard¹,

Cuendet²,

Marliss³

et al. 1973

J. Clin. Invest.

372

238

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A B ST R A C T The metabolic response to the first fast experienced by all mammals has been studied in the newborn rat. Levels of fuels and hormones have been compared in the fetal and maternal circulations at term. Then, after cesarean section just before the normal time of birth, sequential changes in the same parameters were quantified during the first 16 h of the neonatal period. No caloric intake was permitted, and the newborns were maintained at 370C. Activities of three key hepatic enzymes involved in glucose production were estimated.Marked differences in maternal and fetal hormones and fuels were observed. Lower levels of glucose, free fatty acids, and glycerol but higher levels of lactate, a-amino nitrogen, alanine, and glutamine were present in the fetus. Pyruvate, glutamate, and ketone bodies were not significantly different. The combination of a strikingly higher fetal immunoreactive insulin and a slightly lower immunoreactive glucagon (pancreatic) resulted in a profound elevation in the insulin-to-glucagon ratio, a finding consistent with an organism in an anabolic state.The rat at birth presents a body composition with respect to fuels available for mobilization and conversion which is dominated by carbohydrate and protein, since little fat is present. However, at birth a transient period of hypoglycemia occurred, associated with a rapid fall in insulin and rise in glucagon, causing reversal of the insulin-to-glucagon relationship toward ratios such as were observed in the mother. After a lag period, hepatic activities of phosphorylase, glucose-6-phosphatase, and phosphoenolpyruvate carboxykinase increased. Concurrent with these enzyme changes, the blood glucose returned to levels at or above those of the fetus. Interestingly, the fall observed in levels of the gluconeogenic precursors, lactate and amino acids, preceded the rise in enzyme activities and restoration of blood glucose. After 4 h, however, hypoglycemia recurred, during a period of decreasing hepatic glycogen content and blood lactate, pyruvate, and glycerol levels but of stable or increasing amino acid concentrations. Hepatic gluconeogenesis in this phase of depleted glycogen stores was insufficient to maintain euglycemia.Substrates derived from fat showed early changes of smaller magnitude. The rise in free fatty acids which occurred was less than twofold the value at birth, though this rise persisted up to 6 h. Whereas glycerol rose transiently, acetoacetate did not change and P-hydroxybutyrate concentration fell. Both ketone bodies showed a marked rise at 16 h, at a time of diminished free fatty acid levels. Plasma growth hormone, though higher in the fetal than the maternal circulation, showed no consistent change during the period of observation.The changes in levels of the endocrine pancreatic hormones at birth were appropriate in time, magnitude, and direction to be implicated as prime regulators of the metabolic response during the neonatal period in the rat.

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“…Fasting, however, might not lead to sufficiently low glucose levels. Maternal fasting, for example, did not lead to signficant hypoglycemia in the rat fetus (3). The fact that the attainment of very low glucose concentrations might be a prerequisite for the study of alternative cerebral energy fuels has already been suggested by Hinzen et al (10).…”

Section: Discussionmentioning

confidence: 88%

Age-Dependent Utilization of d-β-OH-Butyrate and Oleic Acid as Glucose Substitutes by Neonatal Mouse Brain Cell Cultures

et al. 1982

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Cells 15 days in culture equally oxidized the ketone body throughout the glucose range studied. Oleic acid was increasingly oxidized to C 0 2 by these cells below glucose concentrations of 0.5 mM. Both substrates are alternative cerebral energy sources for glucose. Their utilization varies depending on the developmental stage. SpeculationThe experiments with neonatal mice whole-brain cell cultures demonstrate that d-P-OH-butyrate and oleic acid are utilized as alternative cerebral energy substrates for glucose in an age-depending manner. In the early stages of development, different alternative substrates might be of importance. The results obtained on the cellular level suggest further experiments for testing their physiologic importance in the whole organism.Glucose is the main source for cerebral energy production, but human and animal experiments have shown that ketone bodies and fatty acids may also be utilized by the brain to produce energy (1 1, 17). It is poorly understood at what level of low glucose availability such alternative energy fuels assume importance. Because in vivo experiments at low blood glucose levels are difficult to perform, an in vitro system was chosen consisting of dissociated whole-brain cells from neonatal mice in culture for up to 15 days. The developmental pattern of enzymic activities in these cultures parallels that of the developing mouse brain in vivo (22). The system has proved useful in the study of the effect of low glucose levels on sulfatide synthesis (25), in that hypoglycemia was found to have a similar effect on sulfatide synthesis in vivo (4). Thus, the relevance of this culture system to the in vivo situation has been demonstrated. In prelimi&ry experiments, it was shown that the effects of glucose deprivation on sulfatide synthesis can in part be counteracted by replacing glucose with D-P-OH-butyrate (24). Furthermore, during the first two postnatal wk, the neonatal mouse brain goes through developmental stages that are comparable to the state of maturation of a human brain from the perinatal period up to the first year of age (9).Experiments with brain cell cultures allow the study of metabolic effects directly on the cellular level. Therefore, generalized metabolic effects, as well as the influence of the blood-brain barrier are not taken into account.In the present study, the development of utilization of alternative fuels by the brain, i.e., D-P-OH-butyrate and oleic acid, was investigated in the presence of various low concentrations of glucose. MATERIALS AND METHODSCell cultivation. Cultivation of the brain cells was carried out by the method of Wiesmann et al. (22). Two-16 h after birth, the mice were decapitated and the whole brain was dissociated by repeated pipetting in culture medium containing 10% fetal calf serum. After quantification in a Coulter Counter, 7 million cells were added to 5 ml medium containing 27 mM glucose in a culture flask. To allow for gas exchange the flasks were not closed tightly. Cultivation proceeded at 37OC in a Con-incubator a...

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Sources of Blood Glucose in the Rat Fetus

Cited by 36 publications

References 11 publications

Glucose Production in Pregnant Women at Term Gestation

Glucose Production in Pregnant Women at Term Gestation

Fuels, Hormones, and Liver Metabolism at Term and during the Early Postnatal Period in the Rat

Age-Dependent Utilization of d-β-OH-Butyrate and Oleic Acid as Glucose Substitutes by Neonatal Mouse Brain Cell Cultures

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