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Therapeutic insulin and hepatic glucose-6-phosphatase activity in preterm infants
A Burchell1, A McGeechan, R Hume
1Departments of Obstetrics and Gynaecology and Child Health, Tayside Institute of Child Health, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, UK. a.burchell@dundee.ac.uk
Insights
Insulin administration was unexpectedly linked to higher hepatic glucose-6-phosphatase activity in preterm infants, contrary to animal models. This finding highlights the need for caution when extrapolating results from other models to infant metabolism.
Area of Science:
- Biochemistry
- Neonatal Metabolism
- Enzyme Kinetics
Background:
- Hepatic glucose-6-phosphatase activity is crucial for glucose homeostasis, typically low at birth and rising to adult levels in term infants.
- Preterm infants often exhibit persistently low enzyme activity, increasing risks of hypoglycemia, cerebral damage, and sudden death.
Purpose of the Study:
- To identify clinical factors influencing hepatic glucose-6-phosphatase enzyme activity in preterm infants.
- To understand the determinants of enzyme activity in this vulnerable population.
Main Methods:
- Clinical data from 36 preterm infants were analyzed.
- Stepwise multiple regression was used to correlate clinical variables with Vmax of hepatic glucose-6-phosphatase.
Main Results:
- Insulin administration (units/kg/h postnatal life) showed the most significant positive correlation with hepatic glucose-6-phosphatase Vmax.
- Respiratory distress syndrome and dopamine administration had lesser, but notable, effects.
- Changes in Vmax correlated with alterations in glucose-6-phosphatase protein expression levels.
Conclusions:
- The observed association between insulin administration and increased hepatic glucose-6-phosphatase activity was unexpected, contrasting with findings in animal models.
- Animal models suggest insulin decreases glucose-6-phosphatase gene transcription, a mechanism not reflected in this preterm infant cohort.
- Extrapolation of findings from animal models or adult studies to preterm infant metabolism requires careful consideration due to potential differences.
Background:
Hepatic glucose-6-phosphatase activity is low at birth, and in term infants rises rapidly to adult levels. In contrast, in most preterm infants, it remains low postnatally making them vulnerable to repeated hypoglycaemic episodes, resultant cerebral damage, or risk of sudden and unexpected death.
Aims:
To investigate the clinical features of preterm infants with low glucose-6-phosphatase enzyme activity to determine the influencing factors.
Methods:
Clinical data from 36 preterm infants were correlated by stepwise multiple regression analysis with V(max) of hepatic glucose-6-phosphatase as the dependent variable.
Results:
The most significant correlation was with the administration of insulin (units/kg/h postnatal life) with lesser effects of respiratory distress syndrome and dopamine administration. The V(max) changes reflected changes in the level of expression of the glucose-6-phosphatase protein.
Conclusion:
In a variety of animal models, hepatic glucose-6-phosphatase levels have been shown to decrease in response to insulin, which also decreases transcription of the glucose-6-phosphatase gene. The association of insulin administration with high levels of hepatic glucose-6-phosphatase activity and protein expression was therefore most unexpected. Results from model systems, or adults, must be extrapolated to the metabolism of preterm infants with caution.