Inhibition by recombinant human interleukin-6 of the glucagon-dependent induction of phosphoenolpyruvate carboxykinase and of the insulin-dependent induction of glucokinase gene expression in cultured rat hepatocytes: Regulation of gene transcription and messenger RNA degradation

Hepatology ◽  
1994 ◽  
Vol 20 (6) ◽  
pp. 1577-1583 ◽  
Author(s):  
Bruno Christ Phd. ◽  
Annegret Nath ◽  
Peter C. Heinrich ◽  
Kurt Jungermann
Keyword(s):  
Gene Expression ◽  
Gene Transcription ◽  
Interleukin 6 ◽  
Messenger Rna ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Rat Hepatocytes ◽  
Rna Degradation ◽  
Glucokinase Gene ◽  
Insulin Dependent ◽  
Cultured Rat Hepatocytes

scholarly journals Impairment by interleukin 1β and tumour necrosis factor α of the glucagon-induced increase in phosphoenolpyruvate carboxykinase gene expression and gluconeogenesis in cultured rat hepatocytes

1996 ◽  
Vol 320 (1) ◽  
pp. 161-166 ◽  
Author(s):  
Bruno CHRIST ◽  
Annegret NATH
Keyword(s):  
Gene Expression ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Rat Hepatocytes ◽  
Mrna Levels ◽  
Tumour Necrosis Factor Α ◽  
Maximal Increase ◽  
Cultured Rat Hepatocytes ◽  
Factor Α ◽  
Glucose Formation ◽  
Necrosis Factor

The influence of the inflammatory mediators interleukin 1β (IL1β) and tumour necrosis factor α (TNFα) on the glucagon-induced expression of phosphoenolpyruvate carboxykinase (PCK) and on glucose formation via gluconeogenesis was investigated in cultured rat hepatocytes. Gene expression was monitored by determination of mRNA levels and of enzyme activity. Glucose formation was estimated with newly synthesized radioactive glucose derived from a radiolabelled lactate precursor. Glucagon (0.1 or 1 nM) induced PCK mRNA transiently to a maximum 2 h after its application. In the presence of recombinant human (rh) IL1β or rhTNFα the increase in PCK mRNA levels was totally inhibited at 0.1 nM glucagon, whereas at 1 nM glucagon the maximal increase was inhibited by only 25%. Glucagon (0.1 or 1 nM) induced PCK activity to a maximum after 4 h (4-fold and 6-fold over prestimulatory activity respectively). In the presence of rhIL1β or rhTNFα the maximal increase was inhibited by approx. 50%. Addition of rhIL1β or rhTNFα 2 h after glucagon, at the maximal glucagon-induced PCK mRNA levels, accelerated the decay of PCK mRNA. Glucagon (0.1 or 1 nM) increased glucose formation from lactate by 1.3-fold and 1.7-fold respectively over unstimulated rates. In the presence of rhIL1β or rhTNFα this increase in glucose formation was inhibited by 60–90%. At 0.1 nM, glucagon doubled the intracellular cAMP concentration. This increase was prevented by rhIL1β or rhTNFα. At 1 nM, glucagon increased cAMP concentrations by 10-fold. In the presence of rhIL1β or rhTNFα this increase was inhibited by 70%. From the results it is suggested that rhIL1β and rhTNFα prevented glucagon-stimulated PCK gene expression and gluconeogenesis at least in part by inhibition of the glucagon-stimulated increase in cAMP concentrations.

scholarly journals Involvement of a local Fenton reaction in the reciprocal modulation by O2 of the glucagon-dependent activation of the phosphoenolpyruvate carboxykinase gene and the insulin-dependent activation of the glucokinase gene in rat hepatocytes

1998 ◽  
Vol 335 (2) ◽  
pp. 425-432 ◽  
Author(s):  
Thomas KIETZMANN ◽  
Torsten PORWOL ◽  
Karl ZIEROLD ◽  
Kurt JUNGERMANN ◽  
Helmut ACKER
Keyword(s):  
Hydroxyl Radical ◽  
Hydroxyl Radicals ◽  
Fenton Reaction ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Gene Activation ◽  
Three Dimensional ◽  
Rat Hepatocytes ◽  
Confocal Laser ◽  
Radical Scavenger ◽  
Insulin Dependent

H2O2 mimicked the action of periportal pO2 in the modulation by O2 of the glucagon-dependent activation of the phosphoenolpyruvate carboxykinase (PCK) gene and the insulin-dependent activation of the glucokinase (GK) gene. H2O2 can be converted in the presence of Fe2+ in a Fenton reaction into hydroxyl anions and hydroxyl radicals (•OH). The hydroxyl radicals are highly reactive and might interfere locally with transcription factors. It was the aim of the present study to investigate the role of and to localize such a Fenton reaction. Hepatocytes cultured for 24 h were treated under conditions mimicking periportal or perivenous pO2 with glucagon or insulin plus the iron chelator desferrioxamine (DSF) or the hydroxyl radical scavenger dimethylthiourea (DMTU) to inhibit the Fenton reaction. PCK mRNA was induced by glucagon maximally under conditions of periportal pO2 and half-maximally under venous pO2. GK mRNA was induced by insulin with reciprocal modulation by O2. DSF and DMTU reduced the induction of PCK mRNA to about half-maximal and increased the induction of GK mRNA to maximal under both O2 tensions. Hydroxyl radical formation was maximal under arterial pO2. Perivenous pO2, DSF and DMTU each decreased the formation of •OH to about 70% of control. The Fenton reaction could be localized in a perinuclear space by confocal laser microscopy and three-dimensional reconstruction techniques. In the same compartment, iron could be detected by electron-probe X-ray microanalysis. Thus a local Fenton reaction is involved in the O2 signalling, which modulated the glucagon- and insulin-dependent PCK gene and GK gene activation.

scholarly journals Temporal Gene Expression Analysis of Monolayer Cultured Rat Hepatocytes

2001 ◽  
Vol 14 (9) ◽  
pp. 1218-1231 ◽  
Author(s):  
Thomas K. Baker ◽  
Mark A. Carfagna ◽  
Hong Gao ◽  
Ernst R. Dow ◽  
Qingqin Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Analysis ◽  
Gene Expression Analysis ◽  
Rat Hepatocytes ◽  
Temporal Gene Expression ◽  
Cultured Rat Hepatocytes
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