Effect of dibutyryl cyclic AMP on glucose-6-phosphatase activity in human fetal liver explants

Alan L. Schwartz; Niels C.R. Räihä; Theodore W. Rall

doi:10.1016/0304-4165(74)90267-0

Effect of dibutyryl cyclic AMP on glucose-6-phosphatase activity in human fetal liver explants

Alan L. Schwartz, Niels C.R. Räihä, Theodore W. Rall

Research output: Contribution to journal › Article › peer-review

10 Scopus citations

Abstract

Glucose-6-phosphatase (EC 3.1.3.9) activity in human fetal liver remains constant at 8-28 nmoles/min per mg protein from the 8th week of gestation to at least week 28 and this value is approximately 25-35% of that found in the adult. This enzyme activity was well maintained for 2-3 days in organ culture of fetal liver explants. Incubation with dibutyryl cyclic AMP (0.1 mM) and theophylline (0.5 mM) increased glucose-6-phosphatase activity 4-8-fold within 24 h. Theophylline alone was ineffective, but markedly potentiated the effects of dibutyryl cyclic AMP. This increase in enzyme activity was completely abolished by simultaneous incubation with cycloheximide or actinomycin D. Insulin clearly decreased glucose-6-phosphatase activity in control tissues after 24 h incubation and tended to diminish the elevated glucose-6-phosphatase activity which resulted from pre-incubation with dibutyryl cyclic AMP. The smallest specimen obtained (36 mm crown-rump length = 6 weeks gestation) was capable of elevating glucose-6-phosphatase activity more than 3-fold in response to dibutyryl cyclic AMP incubation, suggesting that the human fetal liver has the competence to respond to hormonal agents at a very early stage of development.

Original language	English
Pages (from-to)	500-509
Number of pages	10
Journal	BBA - General Subjects
Volume	343
Issue number	3
DOIs	https://doi.org/10.1016/0304-4165(74)90267-0
State	Published - May 24 1974

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title = "Effect of dibutyryl cyclic AMP on glucose-6-phosphatase activity in human fetal liver explants",

abstract = "Glucose-6-phosphatase (EC 3.1.3.9) activity in human fetal liver remains constant at 8-28 nmoles/min per mg protein from the 8th week of gestation to at least week 28 and this value is approximately 25-35% of that found in the adult. This enzyme activity was well maintained for 2-3 days in organ culture of fetal liver explants. Incubation with dibutyryl cyclic AMP (0.1 mM) and theophylline (0.5 mM) increased glucose-6-phosphatase activity 4-8-fold within 24 h. Theophylline alone was ineffective, but markedly potentiated the effects of dibutyryl cyclic AMP. This increase in enzyme activity was completely abolished by simultaneous incubation with cycloheximide or actinomycin D. Insulin clearly decreased glucose-6-phosphatase activity in control tissues after 24 h incubation and tended to diminish the elevated glucose-6-phosphatase activity which resulted from pre-incubation with dibutyryl cyclic AMP. The smallest specimen obtained (36 mm crown-rump length = 6 weeks gestation) was capable of elevating glucose-6-phosphatase activity more than 3-fold in response to dibutyryl cyclic AMP incubation, suggesting that the human fetal liver has the competence to respond to hormonal agents at a very early stage of development.",

author = "Schwartz, {Alan L.} and R{\"a}ih{\"a}, {Niels C.R.} and Rall, {Theodore W.}",

note = "Funding Information: The authors acknowledge the excellent technical assistance of Judy Child and are particularly grateful to Dr J. Schlichtkrull of the Novo Research Institute for the gift of insulin and Dr Walter Gall of Merck, Sharp and Dohme for the gift of actinomycin D. This study was supported in part by grants from the Sigrid Juselius Stifelste, Helsinki; the Cleveland Diabetes Fund; and the U.S. Public Health Service grant No. GM-00661-11/-12.",

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AU - Schwartz, Alan L.

AU - Räihä, Niels C.R.

AU - Rall, Theodore W.

N1 - Funding Information: The authors acknowledge the excellent technical assistance of Judy Child and are particularly grateful to Dr J. Schlichtkrull of the Novo Research Institute for the gift of insulin and Dr Walter Gall of Merck, Sharp and Dohme for the gift of actinomycin D. This study was supported in part by grants from the Sigrid Juselius Stifelste, Helsinki; the Cleveland Diabetes Fund; and the U.S. Public Health Service grant No. GM-00661-11/-12.

PY - 1974/5/24

Y1 - 1974/5/24

N2 - Glucose-6-phosphatase (EC 3.1.3.9) activity in human fetal liver remains constant at 8-28 nmoles/min per mg protein from the 8th week of gestation to at least week 28 and this value is approximately 25-35% of that found in the adult. This enzyme activity was well maintained for 2-3 days in organ culture of fetal liver explants. Incubation with dibutyryl cyclic AMP (0.1 mM) and theophylline (0.5 mM) increased glucose-6-phosphatase activity 4-8-fold within 24 h. Theophylline alone was ineffective, but markedly potentiated the effects of dibutyryl cyclic AMP. This increase in enzyme activity was completely abolished by simultaneous incubation with cycloheximide or actinomycin D. Insulin clearly decreased glucose-6-phosphatase activity in control tissues after 24 h incubation and tended to diminish the elevated glucose-6-phosphatase activity which resulted from pre-incubation with dibutyryl cyclic AMP. The smallest specimen obtained (36 mm crown-rump length = 6 weeks gestation) was capable of elevating glucose-6-phosphatase activity more than 3-fold in response to dibutyryl cyclic AMP incubation, suggesting that the human fetal liver has the competence to respond to hormonal agents at a very early stage of development.

AB - Glucose-6-phosphatase (EC 3.1.3.9) activity in human fetal liver remains constant at 8-28 nmoles/min per mg protein from the 8th week of gestation to at least week 28 and this value is approximately 25-35% of that found in the adult. This enzyme activity was well maintained for 2-3 days in organ culture of fetal liver explants. Incubation with dibutyryl cyclic AMP (0.1 mM) and theophylline (0.5 mM) increased glucose-6-phosphatase activity 4-8-fold within 24 h. Theophylline alone was ineffective, but markedly potentiated the effects of dibutyryl cyclic AMP. This increase in enzyme activity was completely abolished by simultaneous incubation with cycloheximide or actinomycin D. Insulin clearly decreased glucose-6-phosphatase activity in control tissues after 24 h incubation and tended to diminish the elevated glucose-6-phosphatase activity which resulted from pre-incubation with dibutyryl cyclic AMP. The smallest specimen obtained (36 mm crown-rump length = 6 weeks gestation) was capable of elevating glucose-6-phosphatase activity more than 3-fold in response to dibutyryl cyclic AMP incubation, suggesting that the human fetal liver has the competence to respond to hormonal agents at a very early stage of development.

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ER -

Effect of dibutyryl cyclic AMP on glucose-6-phosphatase activity in human fetal liver explants

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