Promotion of Adropin Expression by Hyperglycemia Is Associated with STAT3 Activation in Diabetic Rats

Feng Yu Kuo, 1, 2 Kai-Chun Cheng, 3 Yingxiao Li, 4 Juei-Tang Cheng, 5 Cheng-Chia Tsai 6, 7 1Cardiovascular Centre, Kaohsiung Veterans General Hospital, Kaohsiung Citty, Taiwan; 2Department of Pharmacy, College of Pharmacy and Health Care, Tajen University, Pingtung County, Taiwan; 3Pharmacologica...

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Autores principales:	Kuo FY, Cheng KC, Li Y, Cheng JT, Tsai CC
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	adropin enho gene stat3 type-1 diabetes reactive oxygen species Specialties of internal medicine RC581-951
Acceso en línea:	https://doaj.org/article/0f9dc9be362e405c9535aafccc3c2ec2
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spelling	oai:doaj.org-article:0f9dc9be362e405c9535aafccc3c2ec22021-12-02T10:32:51ZPromotion of Adropin Expression by Hyperglycemia Is Associated with STAT3 Activation in Diabetic Rats1178-7007https://doaj.org/article/0f9dc9be362e405c9535aafccc3c2ec22020-06-01T00:00:00Zhttps://www.dovepress.com/promotion-of-adropin-expression-by-hyperglycemia-is-associated-with-st-peer-reviewed-article-DMSOhttps://doaj.org/toc/1178-7007Feng Yu Kuo, 1, 2 Kai-Chun Cheng, 3 Yingxiao Li, 4 Juei-Tang Cheng, 5 Cheng-Chia Tsai 6, 7 1Cardiovascular Centre, Kaohsiung Veterans General Hospital, Kaohsiung Citty, Taiwan; 2Department of Pharmacy, College of Pharmacy and Health Care, Tajen University, Pingtung County, Taiwan; 3Pharmacological Department of Herbal Medicine and Department of Psychosomatic Internal Medicine, Graduate School of Medical and Dental Sciences, Kagoshima Unuversity, Kagoshima, Japan; 4Department of Nursing, Tzu Chi University of Science and Technology, Hualien 97005, Taiwan; 5Department of Medical Research, Chi-Mei Medical Center, Tainan, Taiwan; 6Department of Surgery, Mackay Memorial Hospital, Taipei City, Taiwan; 7Department of Medicine, Mackay Medical College, New Taipei, TaiwanCorrespondence: Juei-Tang ChengDepartment of Medical Research, Chi-Mei Medical Center, No. 901, Zhonghua Road Yongkang District, Tainan 71004, TaiwanTel +886-6-2517864Email jtcheng5503@gmail.comCheng-Chia TsaiDepartment of Surgery, Mackay Memorial Hospital, No. 92, Sec.2, Chung-Shan North Road, Taipei City 10449, TaiwanTel +886-2-25433535Email angle@ms1.mmh.org.twBackground: Adropin is a secreted polypeptide that has been demonstrated to play an important role in energy homeostasis and lipid metabolism. Signal transducer and activator of transcription 3 (STAT3) may promote the transcription of target genes including adropin. In the current study, we investigated the effect of adropin on glucose metabolism in diabetic rats and the mechanism that governs this effect was subsequently assessed.Materials and Methods: Rats received a single injection of streptozotocin to induce type 1 diabetes. The diabetic rats were treated with insulin or phloridzin, another antidiabetic agent through inhibition of glucose reabsorption, for 7 days. Plasma glucose levels and adropin levels were measured. The interaction between STAT3 and adropin was evaluated using the human hepatoma HepG2 cell line. HepG2 cells were pretreated with the specific antagonist Stattic or with STAT3-specific siRNAs to knockout STAT3. Changes in energy homeostasis-associated gene expression were measured using real-time PCR. The protein expression levels of pSTAT3 and STAT3 were measured using Western blotting.Results: In diabetic rats, the serum concentrations of adropin were increased in the vehicle-treated group and decreased in the insulin- or phloridzin-treated group. In liver tissues, the Enho expression level and the activity of STAT3 also showed similar tendencies. After HepG2 cells were treated with medium containing high glucose, the ratio of p-STAT3 to STAT3, Enho mRNA levels and reactive oxygen species expression levels in HepG2 cells were significantly increased in conjunction with increased glucose levels. The effect was inhibited after pretreatment with Stattic or knockdown with STAT3-specific siRNAs.Conclusion: STAT3 is involved in the genetic regulation of adropin, increasing the levels of circulating adropin and promoting Enho expression in the livers of diabetic rats.Keywords: adropin, Enho gene, STAT3, type 1 diabetes, reactive oxygen speciesKuo FYCheng KCLi YCheng JTTsai CCDove Medical Pressarticleadropinenho genestat3type-1 diabetesreactive oxygen speciesSpecialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol Volume 13, Pp 2269-2277 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	adropin enho gene stat3 type-1 diabetes reactive oxygen species Specialties of internal medicine RC581-951
spellingShingle	adropin enho gene stat3 type-1 diabetes reactive oxygen species Specialties of internal medicine RC581-951 Kuo FY Cheng KC Li Y Cheng JT Tsai CC Promotion of Adropin Expression by Hyperglycemia Is Associated with STAT3 Activation in Diabetic Rats
description	Feng Yu Kuo, 1, 2 Kai-Chun Cheng, 3 Yingxiao Li, 4 Juei-Tang Cheng, 5 Cheng-Chia Tsai 6, 7 1Cardiovascular Centre, Kaohsiung Veterans General Hospital, Kaohsiung Citty, Taiwan; 2Department of Pharmacy, College of Pharmacy and Health Care, Tajen University, Pingtung County, Taiwan; 3Pharmacological Department of Herbal Medicine and Department of Psychosomatic Internal Medicine, Graduate School of Medical and Dental Sciences, Kagoshima Unuversity, Kagoshima, Japan; 4Department of Nursing, Tzu Chi University of Science and Technology, Hualien 97005, Taiwan; 5Department of Medical Research, Chi-Mei Medical Center, Tainan, Taiwan; 6Department of Surgery, Mackay Memorial Hospital, Taipei City, Taiwan; 7Department of Medicine, Mackay Medical College, New Taipei, TaiwanCorrespondence: Juei-Tang ChengDepartment of Medical Research, Chi-Mei Medical Center, No. 901, Zhonghua Road Yongkang District, Tainan 71004, TaiwanTel +886-6-2517864Email jtcheng5503@gmail.comCheng-Chia TsaiDepartment of Surgery, Mackay Memorial Hospital, No. 92, Sec.2, Chung-Shan North Road, Taipei City 10449, TaiwanTel +886-2-25433535Email angle@ms1.mmh.org.twBackground: Adropin is a secreted polypeptide that has been demonstrated to play an important role in energy homeostasis and lipid metabolism. Signal transducer and activator of transcription 3 (STAT3) may promote the transcription of target genes including adropin. In the current study, we investigated the effect of adropin on glucose metabolism in diabetic rats and the mechanism that governs this effect was subsequently assessed.Materials and Methods: Rats received a single injection of streptozotocin to induce type 1 diabetes. The diabetic rats were treated with insulin or phloridzin, another antidiabetic agent through inhibition of glucose reabsorption, for 7 days. Plasma glucose levels and adropin levels were measured. The interaction between STAT3 and adropin was evaluated using the human hepatoma HepG2 cell line. HepG2 cells were pretreated with the specific antagonist Stattic or with STAT3-specific siRNAs to knockout STAT3. Changes in energy homeostasis-associated gene expression were measured using real-time PCR. The protein expression levels of pSTAT3 and STAT3 were measured using Western blotting.Results: In diabetic rats, the serum concentrations of adropin were increased in the vehicle-treated group and decreased in the insulin- or phloridzin-treated group. In liver tissues, the Enho expression level and the activity of STAT3 also showed similar tendencies. After HepG2 cells were treated with medium containing high glucose, the ratio of p-STAT3 to STAT3, Enho mRNA levels and reactive oxygen species expression levels in HepG2 cells were significantly increased in conjunction with increased glucose levels. The effect was inhibited after pretreatment with Stattic or knockdown with STAT3-specific siRNAs.Conclusion: STAT3 is involved in the genetic regulation of adropin, increasing the levels of circulating adropin and promoting Enho expression in the livers of diabetic rats.Keywords: adropin, Enho gene, STAT3, type 1 diabetes, reactive oxygen species
format	article
author	Kuo FY Cheng KC Li Y Cheng JT Tsai CC
author_facet	Kuo FY Cheng KC Li Y Cheng JT Tsai CC
author_sort	Kuo FY
title	Promotion of Adropin Expression by Hyperglycemia Is Associated with STAT3 Activation in Diabetic Rats
title_short	Promotion of Adropin Expression by Hyperglycemia Is Associated with STAT3 Activation in Diabetic Rats
title_full	Promotion of Adropin Expression by Hyperglycemia Is Associated with STAT3 Activation in Diabetic Rats
title_fullStr	Promotion of Adropin Expression by Hyperglycemia Is Associated with STAT3 Activation in Diabetic Rats
title_full_unstemmed	Promotion of Adropin Expression by Hyperglycemia Is Associated with STAT3 Activation in Diabetic Rats
title_sort	promotion of adropin expression by hyperglycemia is associated with stat3 activation in diabetic rats
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/0f9dc9be362e405c9535aafccc3c2ec2
work_keys_str_mv	AT kuofy promotionofadropinexpressionbyhyperglycemiaisassociatedwithstat3activationindiabeticrats AT chengkc promotionofadropinexpressionbyhyperglycemiaisassociatedwithstat3activationindiabeticrats AT liy promotionofadropinexpressionbyhyperglycemiaisassociatedwithstat3activationindiabeticrats AT chengjt promotionofadropinexpressionbyhyperglycemiaisassociatedwithstat3activationindiabeticrats AT tsaicc promotionofadropinexpressionbyhyperglycemiaisassociatedwithstat3activationindiabeticrats
_version_	1718397044051148800

Promotion of Adropin Expression by Hyperglycemia Is Associated with STAT3 Activation in Diabetic Rats

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