Role of glucocorticoids in activation of hepatic PEPCK gene transcription during exercise
American Journal of Physiology - Endocrinology and Metabolism, ISSN: 0002-9513, Vol: 266, Issue: 4 29-4, Page: E560-6
1994
- 25Citations
- 14Captures
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Metrics Details
- Citations25
- Citation Indexes25
- 25
- CrossRef6
- Captures14
- Readers14
- 14
Article Description
The objective of these studies was to determine the molecular basis for the activation of phosphoenolpyruvate carboxykinase (PEPCK) gene transcription during prolonged submaximal exercise. Mice were fed a high- carbohydrate diet for 1 wk and exercised continuously by swimming for up to 120 min. The level of hepatic PEPCK mRNA increased progressively during exercise, reaching 510% above control, whereas transcription of the PEPCK gene increased 1,000%, before decreasing to control levels within 60 min of recovery. In transgenic mice carrying a chimeric gene consisting of the PEPCK promoter linked to a reporter gene for bovine growth hormone (bGH), PEPCK(- 460)-bGH, the level of hepatic bGH mRNA increased by 490% in response to exercise, similar to the increase in the expression of the native PEPCK gene. However, in transgenic mice with a deletion of the glucocorticoid regulatory unit, PEPCK(-355)-bGH, bGH mRNA did not increase above control values. In transgenic mice with a block mutation in adenosine 3',5'-cyclic monophosphate (cAMP) regulatory regions -90/-82 and -250/-234, PEPCK cAMP response element 1 (CRE-1)/P3(1)-bGH, exercise increased bGH mRNA 260% above controls. Adrenalectomy (Adx) had no effect on PEPCK mRNA levels in nonexercised mice, whereas in adrenalectomized (Adx)-exercised mice, PEPCK mRNA increased only 80% above basal, and, in Adx mice injected with dexamethasone, PEPCK mRNA increased with exercise 570% above controls. Exercise was also associated with a large increase in transcription of the gene for the transcription factor CCAAT/enhancer-binding protein β (C/EBP-β) and a smaller rise in transcription of c-jun gene, both of which returned to control levels during recovery. These results indicate that transcription of both PEPCK and C/EBP- β gene increase dramatically during exercise and support a possible role for glucocorticoids in the molecular mechanism for activation of hepatic genes involved in energy metabolism during exercise.
Bibliographic Details
http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=0028231673&origin=inward; http://dx.doi.org/10.1152/ajpendo.1994.266.4.e560; http://www.ncbi.nlm.nih.gov/pubmed/8178976; http://www.physiology.org/doi/10.1152/ajpendo.1994.266.4.E560; http://www.physiology.org/doi/pdf/10.1152/ajpendo.1994.266.4.E560; https://www.physiology.org/doi/10.1152/ajpendo.1994.266.4.E560
American Physiological Society
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