Implication of activin E in glucose metabolism: transcriptional regulation of the inhibin/activin betaE subunit gene in the liver.
OBJECTIVE
Activin E is a newly identified member of the transforming growth factor-beta superfamily. To assess the role of activin E in glucose/energy metabolism, we investigated the transcriptional regulation of activin E in the liver.


METHODS
Northern blotting, Western blotting, quantitative real-time polymerase chain reaction (PCR), reporter assays and chromatin immunoprecipitation assays were used in this study.


RESULTS
Insulin up-regulated activin E expression at the mRNA and protein level in HepG2 cells. Reporter assays revealed that the putative, functional, promoter sequence of human activin E gene was responsible for the effect of insulin. Mutational analysis of the promoter revealed that CCAAT/enhancer-binding proteins (C/EBPs) play a key role in regulating activin E expression and in the stimulatory effect of insulin on activin E transcription. Chromatin immunoprecipitation assays revealed that the C/EBPs can bind to the activin E promoter in HepG2 cells. The expression of activin E mRNA was up-regulated in the liver of diet-induced obese mice.


CONCLUSIONS
These observations suggest that activin E plays a pathophysiological role in glucose metabolism.
Hashimoto
Osamu
O
Laboratory of Experimental Animal Science, Faculty of Veterinary Medicine, Kitasato University, School of Veterinary Medicine and Animal Sciences, 35-1 Higashi 23 Bancho, Towada, Aomori 034-8628, Japan. ohashim@vmas.kitasato-u.ac.jp
Sekiyama
Kazunari
K
Matsuo
Tsuyoshi
T
Hasegawa
Yoshihisa
Y
D028341:Activins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D050260:Carbohydrate Metabolism / Q000235:genetics*; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism*; D022781:Hepatocytes / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D028322:Inhibin-beta Subunits / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects
D007004:Hypoglycemic Agents; C504184:Inhbe protein, mouse; D007328:Insulin; D012333:RNA, Messenger; D028341:Activins; D028322:Inhibin-beta Subunits; D005947:Glucose