Pub Date : 2019-09-06Epub Date: 2019-07-19DOI: 10.1074/jbc.RA119.008967
Su Gao, Sarbani Ghoshal, Liyan Zhang, Joseph R Stevens, Kyle S McCommis, Brian N Finck, Gary D Lopaschuk, Andrew A Butler
The peptide hormone adropin regulates energy metabolism in skeletal muscle and plays important roles in the regulation of metabolic homeostasis. Besides muscle, the liver has an essential role in regulating glucose homeostasis. Previous studies have reported that treatment of diet-induced obese (DIO) male mice with adropin34-76 (the putative secreted domain) reduces fasting blood glucose independently of body weight changes, suggesting that adropin suppresses glucose production in the liver. Here, we explored the molecular mechanisms underlying adropin's effects on hepatic glucose metabolism in DIO mice. Male DIO B6 mice maintained on a high-fat diet received five intraperitoneal injections of adropin34-76 (450 nmol/kg/injection) over a 48-h period. We found that adropin34-76 enhances major intracellular signaling activities in the liver that are involved in insulin-mediated regulation of glucose homeostasis. Moreover, treatment with adropin34-76 alleviated endoplasmic reticulum stress responses and reduced activity of c-Jun N-terminal kinase in the liver, explaining the enhanced activities of hepatic insulin signaling pathways observed with adropin34-76 treatment. Furthermore, adropin34-76 suppressed cAMP activated protein kinase A (PKA) activities, resulting in reduced phosphorylation of inositol trisphosphate receptor, which mediates endoplasmic reticulum calcium efflux, and of cAMP-responsive element-binding protein, a key transcription factor in hepatic regulation of glucose metabolism. Adropin34-76 directly affected liver metabolism, decreasing glucose production and reducing PKA-mediated phosphorylation in primary mouse hepatocytes in vitro Our findings indicate that major hepatic signaling pathways contribute to the improved glycemic control achieved with adropin34-76 treatment in situations of obesity.
肽类激素阿多品能调节骨骼肌的能量代谢，在调节代谢平衡方面发挥着重要作用。除肌肉外，肝脏在调节葡萄糖平衡方面也发挥着重要作用。以前的研究报道，用阿糖腺苷34-76（推测的分泌结构域）治疗饮食诱导肥胖（DIO）雄性小鼠可降低空腹血糖，而不受体重变化的影响，这表明阿糖腺苷抑制了肝脏中葡萄糖的生成。在这里，我们探讨了阿动蛋白对 DIO 小鼠肝糖代谢影响的分子机制。以高脂肪饮食饲养的雄性 DIO B6 小鼠在 48 小时内腹腔注射了五次阿动蛋白 34-76（450 nmol/kg/次）。我们发现，阿托品34-76能增强肝脏中参与胰岛素介导的葡萄糖稳态调节的主要细胞内信号活动。此外，阿托品34-76还能缓解内质网应激反应，降低肝脏中c-Jun N-末端激酶的活性，这解释了为什么阿托品34-76能增强肝脏胰岛素信号通路的活性。此外，阿托品34-76还抑制了cAMP激活的蛋白激酶A（PKA）活性，导致介导内质网钙外流的三磷酸肌醇受体和cAMP反应元件结合蛋白的磷酸化减少，而cAMP反应元件结合蛋白是肝脏调节葡萄糖代谢的关键转录因子。我们的研究结果表明，阿托品34-76能改善肥胖症患者的血糖控制，其主要肝脏信号通路功不可没。
{"title":"The peptide hormone adropin regulates signal transduction pathways controlling hepatic glucose metabolism in a mouse model of diet-induced obesity.","authors":"Su Gao, Sarbani Ghoshal, Liyan Zhang, Joseph R Stevens, Kyle S McCommis, Brian N Finck, Gary D Lopaschuk, Andrew A Butler","doi":"10.1074/jbc.RA119.008967","DOIUrl":"10.1074/jbc.RA119.008967","url":null,"abstract":"<p><p>The peptide hormone adropin regulates energy metabolism in skeletal muscle and plays important roles in the regulation of metabolic homeostasis. Besides muscle, the liver has an essential role in regulating glucose homeostasis. Previous studies have reported that treatment of diet-induced obese (DIO) male mice with adropin<sup>34-76</sup> (the putative secreted domain) reduces fasting blood glucose independently of body weight changes, suggesting that adropin suppresses glucose production in the liver. Here, we explored the molecular mechanisms underlying adropin's effects on hepatic glucose metabolism in DIO mice. Male DIO B6 mice maintained on a high-fat diet received five intraperitoneal injections of adropin<sup>34-76</sup> (450 nmol/kg/injection) over a 48-h period. We found that adropin<sup>34-76</sup> enhances major intracellular signaling activities in the liver that are involved in insulin-mediated regulation of glucose homeostasis. Moreover, treatment with adropin<sup>34-76</sup> alleviated endoplasmic reticulum stress responses and reduced activity of c-Jun N-terminal kinase in the liver, explaining the enhanced activities of hepatic insulin signaling pathways observed with adropin<sup>34-76</sup> treatment. Furthermore, adropin<sup>34-76</sup> suppressed cAMP activated protein kinase A (PKA) activities, resulting in reduced phosphorylation of inositol trisphosphate receptor, which mediates endoplasmic reticulum calcium efflux, and of cAMP-responsive element-binding protein, a key transcription factor in hepatic regulation of glucose metabolism. Adropin<sup>34-76</sup> directly affected liver metabolism, decreasing glucose production and reducing PKA-mediated phosphorylation in primary mouse hepatocytes <i>in vitro</i> Our findings indicate that major hepatic signaling pathways contribute to the improved glycemic control achieved with adropin<sup>34-76</sup> treatment in situations of obesity.</p>","PeriodicalId":45966,"journal":{"name":"Southeast Asian Bulletin of Mathematics","volume":"2 1","pages":"13366-13377"},"PeriodicalIF":0.0,"publicationDate":"2019-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6737218/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88910666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2003-06-01DOI: 10.1007/S10012-002-0453-6
M. Parvathi, D. Savithri
{"title":"Representations of G-Brauer Algebras","authors":"M. Parvathi, D. Savithri","doi":"10.1007/S10012-002-0453-6","DOIUrl":"https://doi.org/10.1007/S10012-002-0453-6","url":null,"abstract":"","PeriodicalId":45966,"journal":{"name":"Southeast Asian Bulletin of Mathematics","volume":"117 1","pages":"453-468"},"PeriodicalIF":0.2,"publicationDate":"2003-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/S10012-002-0453-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"52242676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Ideals and Subalgebras in BCI-Algebras","authors":"Wen-Chung Huang, Y. Jun","doi":"10.1007/S100120200060","DOIUrl":"https://doi.org/10.1007/S100120200060","url":null,"abstract":"","PeriodicalId":45966,"journal":{"name":"Southeast Asian Bulletin of Mathematics","volume":"26 1","pages":"567-573"},"PeriodicalIF":0.2,"publicationDate":"2003-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/S100120200060","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"52247547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Injectivity and Graded Injectivity","authors":"Tang Jianliang, Yi Zhong, Cheng Fuchang","doi":"10.1007/S100120200073","DOIUrl":"https://doi.org/10.1007/S100120200073","url":null,"abstract":"","PeriodicalId":45966,"journal":{"name":"Southeast Asian Bulletin of Mathematics","volume":"11 1","pages":"685-691"},"PeriodicalIF":0.2,"publicationDate":"2003-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/S100120200073","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"52248102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2003-06-01DOI: 10.1007/S10012-002-0483-0
J. Rassias
{"title":"On the Hyers-Ulam Stability Problem for Quadratic Multi-dimensional Mappings on the Gaussian Plane","authors":"J. Rassias","doi":"10.1007/S10012-002-0483-0","DOIUrl":"https://doi.org/10.1007/S10012-002-0483-0","url":null,"abstract":"","PeriodicalId":45966,"journal":{"name":"Southeast Asian Bulletin of Mathematics","volume":"26 1","pages":"483-502"},"PeriodicalIF":0.2,"publicationDate":"2003-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/S10012-002-0483-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"52242923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2003-06-01DOI: 10.1007/S10012-002-0535-5
Shao-Xian Xu
{"title":"On the Adjoint Monoids of Implicative BCK-algebras","authors":"Shao-Xian Xu","doi":"10.1007/S10012-002-0535-5","DOIUrl":"https://doi.org/10.1007/S10012-002-0535-5","url":null,"abstract":"","PeriodicalId":45966,"journal":{"name":"Southeast Asian Bulletin of Mathematics","volume":"26 1","pages":"535-540"},"PeriodicalIF":0.2,"publicationDate":"2003-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/S10012-002-0535-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"52244252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"On Positive and Weakly Positive Implicative BCI-Algebras","authors":"Yisheng Huang","doi":"10.1007/S100120200061","DOIUrl":"https://doi.org/10.1007/S100120200061","url":null,"abstract":"","PeriodicalId":45966,"journal":{"name":"Southeast Asian Bulletin of Mathematics","volume":"26 1","pages":"575-582"},"PeriodicalIF":0.2,"publicationDate":"2003-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/S100120200061","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"52247613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Integration by Parts for the Denjoy-Bochner Integral","authors":"Ye Guoju, W. Congxin, Lee Peng Yee","doi":"10.1007/S100120200074","DOIUrl":"https://doi.org/10.1007/S100120200074","url":null,"abstract":"","PeriodicalId":45966,"journal":{"name":"Southeast Asian Bulletin of Mathematics","volume":"26 1","pages":"693-700"},"PeriodicalIF":0.2,"publicationDate":"2003-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/S100120200074","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"52248170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2003-06-01DOI: 10.1007/S10012-002-0523-9
Xiangxing Tao, Songyan Zhang
{"title":"Unique Continuation at the Boundary for Elliptic Operators in Dini Domains","authors":"Xiangxing Tao, Songyan Zhang","doi":"10.1007/S10012-002-0523-9","DOIUrl":"https://doi.org/10.1007/S10012-002-0523-9","url":null,"abstract":"","PeriodicalId":45966,"journal":{"name":"Southeast Asian Bulletin of Mathematics","volume":"26 1","pages":"523-534"},"PeriodicalIF":0.2,"publicationDate":"2003-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/S10012-002-0523-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"52244193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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