Cited by 84Glycogen Storage Diseases and MyoclonusMetabolism, Diabetes, and CancerDiet, Metabolism, and Disease

Development and regulation of glucose-6-phosphatase gene expression in rat liver, intestine, and kidney: in vivo and in vitro studies in cultured fetal hepatocytes.

Chatelain, F, Pégorier, J P, Minassian, C, Bruni, N, Tarpin, S, Girard, J, Mithieux, G·1998·Diabetes

Abstract

The mRNA and the activity of glucose-6-phosphatase (Glc-6-Pase) were present in the liver, kidney, and small intestine of 15-day-old suckling rats, but were absent from the stomach, colon, lung, white and brown adipose tissues, muscle, heart, brain, and spleen. The mRNA encoding Glc-6-Pase was present in the liver of 21-day-old fetal rats and increased markedly immediately after birth. From 5 days after birth to the end of the suckling period, it returned to 50% of the level found in the liver of 48-h starved adult rats. When rats were weaned at 21 days onto a high-carbohydrate, low-fat (HCLF) diet, the concentration of liver Glc-6-Pase mRNA was markedly increased. In the fetal rat jejunum, the activity and mRNA of Glc-6-Pase were very low. It increased during the 5 days after birth and then declined to reach very low levels. Neither mRNA nor activity of Glc-6-Pase was present in the fetal kidney. They appeared and increased slowly during the suckling period to reach maximal levels 15 days after birth and then remained constant. Weaning onto the HCLF diet did not change the Glc-6-Pase gene expression, neither in the jejunum nor in the kidney. The regulation of Glc-6-Pase gene expression by hormones and nutrients was studied in cultured hepatocytes from 20-day-old rat fetuses. Bt2cAMP stimulated the Glc-6-Pase gene expression in a dose-dependent manner. This probably resulted from an increased gene transcription since the half-life of the transcript was not affected by dibutyryl cAMP (Bt2cAMP). The Bt2cAMP-induced Glc-6-Pase mRNA accumulation was antagonized by insulin in a dose-dependent manner. Long-chain fatty acids (LCFAs), but not medium-chain fatty acids, induced the accumulation of Glc-6-Pase mRNA and the stabilization of the transcript. The peroxisome proliferator, clofibrate, induced a threefold increase in Glc-6-Pase mRNA concentration. Both stimulation of Glc-6-Pase mRNA by LCFAs and clofibrate were inhibited by insulin. Increasing concentrations of glucose (from 0 to 20 mmol/l) did not affect the Bt2cAMP-induced Glc-6-Pase gene expression. By contrast, high glucose concentration (25 mmol/l) markedly induced the Glc-6-Pase gene expression in fed adult rat hepatocytes. The difference in the response to glucose between fetal and adult rat hepatocytes is discussed. We conclude that the rapid increase in hepatic Glc-6-Pase mRNA levels that accompanies the fetal-to-neonatal transition in the rat is triggered by the reciprocal change in circulating insulin and LCFA concentrations, coupled to the rise in liver cAMP concentration.

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Crossref · 10.2337/diabetes.47.6.882

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  • Changes in cAMP concentration are directly involved in transcriptional regulation of PEPCK and G-6-Pase genes through several cis-acting sequences in their promoters.

    “Changes in cAMP concentration are also directly involved in transcriptional regulation of these genes through several cis-acting sequences present in their promoters (8).”

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Authors
Chatelain, F., Pégorier, J. P., Minassian, C., Bruni, N., Tarpin, S., Girard, J., & Mithieux, G.
Affiliations
Centre National de la Recherche Scientifique (FR)
Venue
Diabetes
Published
1998-06-01
Volume
47
Issue
6
Pages
882-889
ISSN
  • 0012-1797 (ISSN-L)
  • 1939-327X
OpenAlex
W2070424667
Cited by
83
References
0
Citations by year
2025: 2 · 2024: 3 · 2022: 1 · 2021: 1 · 2019: 3 · 2018: 1 · 2017: 3 · 2016: 2 · 2015: 2 · 2014: 2 · 2013: 4 · 2012: 7
FWCI
5.26
Type
journal article
Language
en
Open access
closed
Locations
  • Diabetes (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Rheumatology › Glycogen Storage Diseases and Myoclonus
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
Keywords
glucose-6-phosphatase, gene expression regulation, fetal hepatocytes, liver, intestine, kidney, postnatal development, weaning diet, cyclic AMP, insulin, long-chain fatty acids, clofibrate, peroxisome proliferators, glucose, gene transcription, mRNA stability, gluconeogenesis, rat fetus, suckling rats, tissue-specific gene expression
MeSH terms
Aging, Animals, Animals, Newborn, Cells, Cultured, Clofibrate, Bucladesine, Dietary Carbohydrates, Fatty Acids, Nonesterified, Fatty Acids, Unsaturated, Female, Fetus, Glucose-6-Phosphatase, Insulin, Intestinal Mucosa, Intestine, Small, Kidney, Liver, Organ Specificity, RNA, Messenger, Transcription, Genetic, Gene Expression Regulation, Enzymologic, Rats, Wistar, Gene Expression Regulation, Developmental, Diet, Fat-Restricted, Rats

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