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Hormonal regulation of key gluconeogenic enzymes and glucose release in cultured hepatocytes: Effects of dexamethasone and gastrointestinal hormones on glucagon action
Abstract
Hormonal regulation of key gluconeogenic enzymes and glucose release by glucagon, dexamethasone, secretin and somatostatin was evaluated in maintenance cultured rat hepatocytes. (i) Phosphoenolpyruvate (PEP)-carboxykinase activity declined rapidly during the first 24 h in serum- and hormone-free culture with a further slight decay during the following 2 days. Dexamethasone and glucagon independently increased PEP-carboxykinase and acted synergistically when added in combination. Glucose-6-phosphatase activity declining linearly during hormone-free culture was stimulated by glucagon. Dexamethasone itself was without significant effects but completely abolished glucagon action. Fructose-1,6-diphosphatase was maintained at its initial level during the first day under control conditions and declined thereafter. Neither glucagon nor dexamethasone affected total activity or substrate (fructose-1,6-diphosphate) affinity of this enzyme. In short-term experiments on cells cultured under control conditions, protein synthesis-dependent stimulation of PEP-carboxykinase by glucagon and the permissive action of dexamethasone was demonstrated. Glucose-6-phosphatase and fructose-1,6-diphosphatase were not altered by hormones within this period. (ii) Stimulation by glucagon of gluconeogenesis was independent of its action on PEP-carboxykinase. Dexamethasone inhibited glycogenolysis but maintained glucose release at control levels probably by stimulation of gluconeogenesis. When added in combination, the glycogen-preserving action of dexamethasone acutely reduced the glucose release in response to glucagon. Glucagon sensitivity remained unchanged. (iii) The gastrointestinal hormones secretin and somatostatin were ineffective in modulating basal or glucagon-stimulated glucose release and gluconeogenic key enzymes. They are therefore unlikely to play a physiological role in hepatic glucose metabolism.
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“Furthermore, phosphoenolpyruvate carboxykinase (PEPCK) activity is increased by glucocorticoids, consistent with an increase in gluconeogenesis during hypercortisolemia (16).”
From Impaired basal glucose effectiveness but unaltered fasting glucose release and gluconeogenesis during short-term hypercortisolemia in healthy subjects (2004) · cites this paper as [16]
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Metadata
- Authors
- Fleig, W. E., Noether-Fleig, G., Roeben, H., & Ditschuneit, H.
- Affiliations
- Universität Ulm (DE)
- Corresponding author
- Fleig, Wolfgang E.
- Venue
- Archives of Biochemistry and Biophysics
- Publisher
- Elsevier BV
- Published
- 1984-02
- Volume
- 229
- Issue
- 1
- Pages
- 368-378
- ISSN
- 0003-9861 (ISSN-L)
- OpenAlex
- W2087445157
- Cited by
- 33
- References
- 67
- Citations by year
- 2023: 1 · 2022: 2 · 2021: 1 · 2012: 1
- FWCI
- 1.63
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of Biochemistry and Biophysics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Glycogen Storage Diseases and Myoclonus
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Keywords
- gluconeogenesis, glucagon, dexamethasone, phosphoenolpyruvate carboxykinase, glucose-6-phosphatase, fructose-1,6-bisphosphatase, hepatocytes, glycogenolysis, secretin, somatostatin, gastrointestinal hormones, hepatic glucose metabolism, glucagon sensitivity, enzyme regulation
- MeSH terms
- Animals, Cells, Cultured, Dexamethasone, Gastrointestinal Hormones, Glucagon, Gluconeogenesis, Glucose, Glucose-6-Phosphatase, Fructose-Bisphosphatase, Liver, Male, Phosphoenolpyruvate Carboxykinase (GTP), Rats, Inbred Strains, Secretin, Somatostatin, Rats
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