Abstract
The activities of pyruvate dehydrogenase (PDH) kinase and of PDH kinase activator protein (KAP) were increased 2-2.4-fold during 25 h of culture of hepatocytes from fed rats with glucagon plus n-octanoate. PDH kinase activity in hepatocytes from starved rats (initially 2.2 x fed control) fell during 25 h of culture in medium 199 (to 1.5 x fed control), but was maintained by glucagon plus octanoate. Dibutyryl or 8-bromo cyclic AMP increased PDH kinase activity 2-2.2-fold in hepatocytes from fed rats, but phenylephrine and isoproterenol (isoprenaline) were without effect. Insulin blocked the action of glucagon to increase PDH kinase activity and decreased the effect of octanoate and octanoate plus glucagon. It is suggested that the effects of starvation to increase activities of PDH kinase and of KAP in liver are mediated by alterations in circulating concentrations of glucagon, fatty acids and insulin and in hepatic cyclic AMP.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- Claus T. H., Pilkis S. J. Regulation by insulin of gluconeogenesis in isolated rat hepatocytes. Biochim Biophys Acta. 1976 Feb 24;421(2):246–262. doi: 10.1016/0304-4165(76)90291-9. [DOI] [PubMed] [Google Scholar]
- Denyer G. S., Kerbey A. L., Randle P. J. Kinase activator protein mediates longer-term effects of starvation on activity of pyruvate dehydrogenase kinase in rat liver mitochondria. Biochem J. 1986 Oct 15;239(2):347–354. doi: 10.1042/bj2390347. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fatania H. R., Vary T. C., Randle P. J. Modulation of pyruvate dehydrogenase kinase activity in cultured hepatocytes by glucagon and n-octanoate. Biochem J. 1986 Feb 15;234(1):233–236. doi: 10.1042/bj2340233. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fuller S. J., Randle P. J. Reversible phosphorylation of pyruvate dehydrogenase in rat skeletal-muscle mitochondria. Effects of starvation and diabetes. Biochem J. 1984 Apr 15;219(2):635–646. doi: 10.1042/bj2190635. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Granner D. K., Sasaki K., Andreone T., Beale E. Insulin regulates expression of the phosphoenolpyruvate carboxykinase gene. Recent Prog Horm Res. 1986;42:111–141. doi: 10.1016/b978-0-12-571142-5.50007-0. [DOI] [PubMed] [Google Scholar]
- Houslay M. D. Insulin, glucagon and the receptor-mediated control of cyclic AMP concentrations in liver. Twenty-second Colworth medal lecture. Biochem Soc Trans. 1986 Apr;14(2):183–193. doi: 10.1042/bst0140183. [DOI] [PubMed] [Google Scholar]
- Hutson N. J., Randle P. J. Enhanced activity of pyruvate dehydrogenase kinase in rat heart mitochondria in alloxan-diabetes or starvation. FEBS Lett. 1978 Aug 1;92(1):73–76. doi: 10.1016/0014-5793(78)80724-8. [DOI] [PubMed] [Google Scholar]
- Issad T., Pénicaud L., Ferré P., Kandé J., Baudon M. A., Girard J. Effects of fasting on tissue glucose utilization in conscious resting rats. Major glucose-sparing effect in working muscles. Biochem J. 1987 Aug 15;246(1):241–244. doi: 10.1042/bj2460241. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kerbey A. L., Randle P. J. Pyruvate dehydrogenase kinase/activator in rat heart mitochondria, Assay, effect of starvation, and effect of protein-synthesis inhibitors of starvation. Biochem J. 1982 Jul 15;206(1):103–111. doi: 10.1042/bj2060103. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kerbey A. L., Randle P. J. Thermolabile factor accelerates pyruvate dehydrogenase kinase reaction in heart mitochondria of starved or alloxan-diabetic rats. FEBS Lett. 1981 May 18;127(2):188–192. doi: 10.1016/0014-5793(81)80201-3. [DOI] [PubMed] [Google Scholar]
- Kerbey A. L., Richardson L. J., Randle P. J. The roles of intrinsic kinase and of kinase/activator protein in the enhanced phosphorylation of pyruvate dehydrogenase complex in starvation. FEBS Lett. 1984 Oct 15;176(1):115–119. doi: 10.1016/0014-5793(84)80923-0. [DOI] [PubMed] [Google Scholar]
- Linn T. C., Pettit F. H., Reed L. J. Alpha-keto acid dehydrogenase complexes. X. Regulation of the activity of the pyruvate dehydrogenase complex from beef kidney mitochondria by phosphorylation and dephosphorylation. Proc Natl Acad Sci U S A. 1969 Jan;62(1):234–241. doi: 10.1073/pnas.62.1.234. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Marchington D. R., Kerbey A. L., Jones A. E., Randle P. J. Insulin reverses effects of starvation on the activity of pyruvate dehydrogenase kinase in cultured hepatocytes. Biochem J. 1987 Aug 15;246(1):233–236. doi: 10.1042/bj2460233. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Park C. R., Lewis S. B., Exton J. H. Relationship of some hepatic actions of insulin to the intracellular level of cyclic adenylate. Diabetes. 1972;21(2 Suppl):439–446. doi: 10.2337/diab.21.2.s439. [DOI] [PubMed] [Google Scholar]
- Pilkis S. J., Claus T. H., Johnson R. A., Park C. R. Hormonal control of cyclic 3':5'-AMP levels and gluconeogenesis in isolated hepatocytes from fed rats. J Biol Chem. 1975 Aug 25;250(16):6328–6336. [PubMed] [Google Scholar]