The ontogeny of human hepatic microsomal glucose-6-phosphatase proteins

Abstract

We have studied 250 human liver biopsy samples to determine the ontogeny of the microsomal glucose-6-phosphatase (EC 3.1.3.9) system. Human hepatic glucose-6-phosphatase enzyme activity develops at 11 weeks' gestation and slowly increases to approximately 10% of adult activity at term. In the first week after birth, activity rises to adult values. Increases in enzyme activity coincide with increasing concentrations of the glucose-6-phosphatase enzyme protein. The phosphate/pyrophosphate transport protein (T2) of the human hepatic glucose-6-phosphatase complex develops at a different rate from that of the enzyme. Our study shows that the development of rat and human glucose-6-phosphatase activities are completely different. We conclude that deficiencies of the proteins in the microsomal glucose-6-phosphatase complex can be diagnosed with much more certainty perinatally than prenatally.

Developmental disorders of glucose metabolism in infants

“…This indicates hepatic immaturity in the response to counter‐regulatory hormones. It is consistent with the low levels of hepatic glucose‐6‐phosphatase activity in premature infants (Burchell et al. 1990; Hume et al.…”

Impairment of the activity of the hepatic microsomal glucose‐6‐phosphatase system in three preterm infants

“…To date we have studied the hepatic microsomal glucose-6-phosphatase system in over 500 human liver samples (3,4, [10][11][12][13][14][15][16]22). The control values of glucose-6-phosphatase activity in term infants reported in Tables 1 and 2 are within the normal range of values that we have found previously in both term infants over one week of age and in adults (3, 4, [10][11][12][13][14][15][16]22).…”

“…The Apgar scores were 8 and 9 at 1 and 5 min and the birth weight was 947 g, appropriate for gestational age. The neonatal period was complicated by respiratory distress syndrome requiring intermittent positive pressure ventilation, pneumomediastinum, systemic candidiasis with pneumonia (treated with amphotericin B and flucytosine for days [16][17][18][19][20][21][22][23][24][25][26] and bronchopulmonary dysplasia (treated with dexamethasone (1 5 ) for days 29-56 and frusemide for days 162-266). Ventilatory support continued until day 36 when he was extubated but he remained oxygen dependent until day 210.…”

Regulation of liver glucose production

“…Liver glucose‐6‐phosphatase is developmentally regulated. Prior to birth when glucose is supplied across the placenta glucose‐6‐phosphatase activity is low 4 …”

“…In most (but not all) term infants glucose‐6‐phosphatase activity increases dramatically at birth reaching adult levels within approximately 2 days 4 . In contrast, in many preterm infants, activity does not increase postnatally (or the rise is very blunted) and can remain low for several months 5 , 6 .…”