The Newborn of Diabetic Rat. I. Hormonal and Metabolic Changes in the Postnatal Period

Cuezva, José M.; Burkett, Edward; Kerr, Douglas S.; Rodman, Harvey M.; Patel, Mulchand S.

doi:10.1203/00006450-198208000-00009

Cited by 57 publications

(67 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, it has been shown that injection of glucagon or CAMP to fetal rats in utero causes a marked induction of mRNA for phosphoenolpyruvate carboxykinase which suggests a regulation of phosphoenolpyruvate carboxykinase synthesis by this hormone (9). Conversely, newborn rats of diabetic mothers exhibit a high plasma insu1in:glucagon ratio associated with an impaired development of gluconeogenesis after birth (38,39). Similarly, a decrease in the plasma insu1in:glucagon molar ratio must favor a low lipogenic rate and a high rate of fatty acid oxidation (25,(40)(41)(42).…”

Section: Discussionmentioning

confidence: 99%

Premature Appearance of Gluconeogenesis and Fatty Acid Oxidation in the Liver of the Postterm Rabbit Fetus

et al. 1988

View full text Add to dashboard Cite

ABSTRACT. The metabolic consequences of a prolonged gestation (35 vs 32 days) have been studied in the rabbit fetus. Gestation was prolonged by daily subcutaneous injections of progesterone (1.5 mg-kg-') from day 28 to 34. In control animals, progesterone was injected from day 25 or 28 to day 31 of gestation. When the capacities for gluconeogenesis and fatty acid oxidation, measured on isolated hepatocytes, are normally low in the term control fetus and increase only within the first 24 h after birth, these capacities appear high in the postmature fetus. The rate of glucose production from lactate is 4-fold higher in the postmature fetus than in the normal term fetus. The rate of ketone body production from oleate is also 5-fold higher in the postmature fetus, which results from a switch on of the partition of oleate into esterification and oxidation: 8% of [1-14Cjoleate is oxidized in term fetus hepatocytes, but 34% in postmature fetus hepatocytes. As a similar rate of lipogenesis takes place in both stages, this metabolic change could be explained by a 5-fold lower sensitivity of carnitine palmitoyltransferase I to the inhibition by malonyl-coenzyme A. Postmaturity decreases plasma insulin concentrations by 45% and increases plasma glucagon concentrations by 50% which, in turn, induces a 3-fold decrease in the plasma insu1in:glucagon molar ratio. As previously shown in fasted or diabetic adult rat, this hormonal change might be a likely candidate for an enhancement of gluconeogenic and ketogenic capacity in the liver of the postterm rabbit fetus. (Pediatr Res 23: 224-228,1988) Abbreviation CoA, coenzyme A During pregnancy, the fetus receives a continuous supply of nutrients, principally glucose and amino acids for its growth and its oxidative metabolism which makes unnecessary the development of metabolic pathways as those involved in endogenous glucose production or free fatty acid oxidation (1). Previous studies performed in rabbit hepatocytes have shown that gluconeogenesis from lactate or oleate oxidation and ketogenesis proceed to a very low rate in term fetus and increase during the first day after birth (2, 3). The postnatal emergence of hepatic gluconeogenesis and fatty acid oxidation correspond to a shifting of Received July 31, 1987; accepted October 14, 1987. Correspondence and reprint requests Pierre-Henri Duk, Centre de Recherches sur la Nutrition, CNRS, 9 rue Jules Hetzel, 92 190 Meudon-Bellevue, France.Supported in part by Grant CRE 867010 from the Institut National de la Santt et de la Recherche MCdicale. specific limiting steps that have been well described. The emergence of hepatic gluconeogenesis in the newborn rabbit may result from a rapid fall in hepatic fructose 2,6-bisphosphate concentration (4) and from an increase in the activity of cytosolic phosphoenolpyruvate carboxykinase (2). Moreover, it has been shown that the postnatal increase in mitochondria1 adenine nucleotide content stimulates pyruvate carboxylation causing a rapid increase in the rate of hepatic gluconeogenesis (5,...

show abstract

Section: Discussionmentioning

confidence: 99%

Premature Appearance of Gluconeogenesis and Fatty Acid Oxidation in the Liver of the Postterm Rabbit Fetus

et al. 1988

View full text Add to dashboard Cite

show abstract

“…[23][24][25][26][27][28][29] Figure 10A shows our experimental protocol in detail. As may be seen, the newborn offspring of STZ-induced diabetic dams remained significantly smaller and lighter (average 20% less body weight) as compared with offspring of control dams (control versus STZ: 1.414 Ϯ 0.11 versus 1.03 Ϯ 0.07 g; Figure 10B).…”

Section: Effect Of Gestational Diabetes On Offspring Neonatal Kidneymentioning

confidence: 99%

“…[23][24][25][26][27][28][29] Maternal glucose concentration (mM) was carefully monitored by Accu-Chek Compact Plus Blood Glucose Meter (Roche Diagnostics, Laval, QC, Canada; Figure 10 A). Newborn birth weight was carefully recorded, as shown in Figure 10B.…”

Section: In Vivo Studymentioning

confidence: 99%

Reactive Oxygen Species in the Presence of High Glucose Alter Ureteric Bud Morphogenesis

Zhang

Chen

Tran

et al. 2007

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

Renal malformations are a major cause of childhood renal failure. During the development of the kidney, ureteric bud (UB) branching morphogenesis is critical for normal nephrogenesis. These studies investigated whether renal UB branching morphogenesis is altered by a high ambient glucose environment and studied underlying mechanism(s). Kidney explants that were isolated from different periods of gestation (embryonic days 12 to 18) from Hoxb7-green fluorescence protein mice were cultured for 24 h in either normal D-glucose (5 mM) or high D-glucose (25 mM) medium with or without various inhibitors. Alterations in renal morphogenesis were assessed by fluorescence microscopy. Paired-homeobox 2 (Pax-2) gene expression was determined by real-time quantitative PCR, Western blotting, and immunohistology. The results revealed that high D-glucose (25 mM) specifically stimulates UB branching morphogenesis via Pax-2 gene expression, whereas other glucose analogs, such as D-mannitol, L-glucose, and 2-deoxy-Dglucose, had no effect. The stimulatory effect of high glucose on UB branching was blocked in the presence of catalase and inhibitors of NADPH oxidase, mitochondrial electron transport chain complex I, and Akt signaling. Moreover, in in vivo studies, it seems that high glucose induces, via Pax-2 (mainly localized in UB), acceleration of UB branching but not nephron formation. Taken together, these data demonstrate that high glucose alters UB branching morphogenesis. This occurs, at least in part, via reactive oxygen species generation, activation of Akt signaling, and upregulation of Pax-2 gene expression.

show abstract

“…The streptozotocin model for maternal diabetes used herein has been well characterized; maternal weight gain is the same as in controls and newborn weights are decreased only slightly (24). The slower rate of adenine nucleotide uptake into liver mitochondria in pups of diabetic mothers that we observed is probably due to the higher than normal insulin/glucagon ratio in these newborns (24,27) (Tullson PC, Aprille JR, unpublished data).…”

Section: Discussionmentioning

confidence: 80%

“…In previous work the postnatal increase in the matrix ATP content was shown to stimulate pyruvate carboxylation (7,8), which is rate-limiting for gluconeogenesis at birth (9,23). Herein we have shown that adenine nucleotide accumulation by mitochondria is delayed by neonatal hypoxia and in pups of diabetic mothers; this delay may retard the rapid onset of gluconeogenesis and thus contribute to the problematic postnatal hypoglycemia that is characteristic of these groups of newborns (12,13,24).…”

Section: Discussionmentioning

confidence: 81%

Neonatal Hypoxia or Maternal Diabetes Delays Postnatal Development of Liver Mitochondria

Aprille

Nosek

1987

Pediatr Res

View full text Add to dashboard Cite

ABSTRACT. The matrix adenine nucleotide pool size of rat liver mitochondria was low at birth (2.6-3.0 nmol ATP+ADP+AMP/mg mitochondrial protein). After parturition, the pool size was increased by 50-75% within 1 h, which was sufficient for full development of state 3 respiration rates. The adenine nucleotide pool size continued to increase to 100-150% of the value at birth by 2-3 h postnatal. The ATPIADP ratio in isolated mitochondria also increased postnatally, to about double the value at birth by 3 h. There were no matrix volume changes over this postnatal period, so the increased ATP+ADP+AMP pool size and the increased ATPIADP ratio together inferred an overall increase of about 5-fold in the matrix ATP concentration under aerobic conditions. The postnatal uptake of adenine nucleotides into mitochondria occurred at a slower rate in newborns that were hypoxic (11% Oz) and in newborns of diabetic mothers (diabetes induced on day 5 of gestation by streptozotocin injection). The normal increase in matrix ATP content is responsible for the rapid stimulation of pyruvate carboxylation (an ATP-requiring matrix reaction) and this in turn contributes to the rapid postnatal onset of gluconeogenesis. The results suggest that delayed adenine nucleotide uptake into liver mitochondria may retard initiation of gluconeogenesis in newborns experiencing hypoxia, as in respiratory distress or in newborns of diabetic mothers. We speculate that this mechanism contributes to the persistent hypoglycemia that is typical of these at-risk newborns. (Pediatr Res 21: 266-269,1987) Mitochondria isolated from full-term fetal rat liver are functionally well coupled, but the rate of oxidative phosphorylation (state 3 respiration) is very low (reviewed in Reference 1). Within 1 h after birth, the state 3 rate increases to adult values (2-4). This functional maturation depends on a rapid increase in the mitochondrial adenine nucleotide content (ATP+ADP+AMP) which occurs in the immediate postnatal period (2, 4-6) In addition to activating state 3 respiration the increased adenine nucleotide pool size may also stimulate metabolic pathways that have adenine nucleotide-dependent enzymes within the mitochondrial compartment (reviewed in Reference 1). One matrix enzyme subject to this kind of control is pyruvate carboxylase. In both the newborn rat and rabbit the sudden postnatal increase in the matrix ATP concentration enhances pyruvate carboxylation rates enabling the onset of gluconeogenesis and recovery from postnatal hypoglycemia (7-9). Thus, the accumulation of adenine nucleotides into the mitochondria appears to be important for metabolic adaptation to neonatal life (see Reference 1).Received May 13, 1986; accepted October 23, 1986. Correspondence and reprint requests Dr. June R. Aprille, Mitochondria1 Physiology Unit, Department of Biology, Tufts University, Medford, MA 02155.Supported by NIH Grants HD 16936 and NS 14936.There is considerable evidence that hormones and oxygenation are important controlling factors for the subcellular red...

show abstract

The Newborn of Diabetic Rat. I. Hormonal and Metabolic Changes in the Postnatal Period

Cited by 57 publications

References 14 publications

Premature Appearance of Gluconeogenesis and Fatty Acid Oxidation in the Liver of the Postterm Rabbit Fetus

Premature Appearance of Gluconeogenesis and Fatty Acid Oxidation in the Liver of the Postterm Rabbit Fetus

Reactive Oxygen Species in the Presence of High Glucose Alter Ureteric Bud Morphogenesis

Neonatal Hypoxia or Maternal Diabetes Delays Postnatal Development of Liver Mitochondria

Contact Info

Product

Resources

About