Inhibition of insulin resistance by PGE1 via autophagy-dependent FGF21 pathway in diabetic nephropathy
Insulin resistance is a critical process in the initiation and progression of diabetic nephropathy (DN). Alprostadil (Prostaglandin E1, PGE1) had protective effects on renal function. However, it is unknown whether PGE1 inhibited insulin resistance in renal tubule epithelial cells via autophagy, whi...
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| description | Insulin resistance is a critical process in the initiation and progression of diabetic nephropathy (DN). Alprostadil (Prostaglandin E1, PGE1) had protective effects on renal function. However, it is unknown whether PGE1 inhibited insulin resistance in renal tubule epithelial cells via autophagy, which plays a protective role in DN against insulin resistance. Insulin resistance was induced by palmitic acid (PA) in human HK-2 cells, shown as the decrease of insulin-stimulated AKT phosphorylation, glucose transporter-4 (GLUT4), glucose uptake and enhanced phosphorylation of insulin receptor substrate 1(IRS-1) at site serine 307 (pIRS-1ser307) and downregulated expression of IRS-1. Along with less abundance of p62, autophagy markers LC3B and Beclin-1 significantly increased in HK-2 cells exposed to PA. Such abnormal changes were significantly reversed by PGE1, which mimicked the role of autophagy gene 7 small interfering RNA (ATG7 siRNA). Furthermore, PGE1 promoted the protein expression of autophagy-related fibroblast growth factor-21 (FGF21), which alleviated insulin resistance. Results from western blotting and immunohistochemistry indicated that PGE1 remarkably restored autophagy, insulin resistance and the FGF21 expression in rat kidney of type 2 diabetes mellitus (T2DM). Collectively, we demonstrated the potential protection of PGE1 on insulin resistance in renal tubules via autophagy-dependent FGF21 pathway in preventing the progression of DN. |
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Alprostadil (Prostaglandin E1, PGE1) had protective effects on renal function. However, it is unknown whether PGE1 inhibited insulin resistance in renal tubule epithelial cells via autophagy, which plays a protective role in DN against insulin resistance. Insulin resistance was induced by palmitic acid (PA) in human HK-2 cells, shown as the decrease of insulin-stimulated AKT phosphorylation, glucose transporter-4 (GLUT4), glucose uptake and enhanced phosphorylation of insulin receptor substrate 1(IRS-1) at site serine 307 (pIRS-1ser307) and downregulated expression of IRS-1. Along with less abundance of p62, autophagy markers LC3B and Beclin-1 significantly increased in HK-2 cells exposed to PA. Such abnormal changes were significantly reversed by PGE1, which mimicked the role of autophagy gene 7 small interfering RNA (ATG7 siRNA). Furthermore, PGE1 promoted the protein expression of autophagy-related fibroblast growth factor-21 (FGF21), which alleviated insulin resistance. Results from western blotting and immunohistochemistry indicated that PGE1 remarkably restored autophagy, insulin resistance and the FGF21 expression in rat kidney of type 2 diabetes mellitus (T2DM). Collectively, we demonstrated the potential protection of PGE1 on insulin resistance in renal tubules via autophagy-dependent FGF21 pathway in preventing the progression of DN.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-017-18427-2</identifier><identifier>PMID: 29311680</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/51 ; 13/95 ; 14/19 ; 14/35 ; 692/163/2743/137/138 ; 692/4022/1585/104/1586 ; 82/80 ; AKT protein ; Autophagy ; Diabetes ; Diabetes mellitus ; Diabetes mellitus (non-insulin dependent) ; Diabetic nephropathy ; Epithelial cells ; Fibroblast growth factors ; Glucose ; Glucose transporter ; Humanities and Social Sciences ; Immunohistochemistry ; Insulin ; Insulin receptor substrate 1 ; Insulin resistance ; multidisciplinary ; Nephropathy ; Palmitic acid ; Phagocytosis ; Phosphorylation ; Prostaglandin E1 ; Renal function ; Renal tubules ; Rodents ; Science ; Science (multidisciplinary) ; Serine ; siRNA ; Western blotting</subject><ispartof>Scientific reports, 2018-01, Vol.8 (1), p.9-9, Article 9</ispartof><rights>The Author(s) 2017</rights><rights>2017. 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Alprostadil (Prostaglandin E1, PGE1) had protective effects on renal function. However, it is unknown whether PGE1 inhibited insulin resistance in renal tubule epithelial cells via autophagy, which plays a protective role in DN against insulin resistance. Insulin resistance was induced by palmitic acid (PA) in human HK-2 cells, shown as the decrease of insulin-stimulated AKT phosphorylation, glucose transporter-4 (GLUT4), glucose uptake and enhanced phosphorylation of insulin receptor substrate 1(IRS-1) at site serine 307 (pIRS-1ser307) and downregulated expression of IRS-1. Along with less abundance of p62, autophagy markers LC3B and Beclin-1 significantly increased in HK-2 cells exposed to PA. Such abnormal changes were significantly reversed by PGE1, which mimicked the role of autophagy gene 7 small interfering RNA (ATG7 siRNA). Furthermore, PGE1 promoted the protein expression of autophagy-related fibroblast growth factor-21 (FGF21), which alleviated insulin resistance. Results from western blotting and immunohistochemistry indicated that PGE1 remarkably restored autophagy, insulin resistance and the FGF21 expression in rat kidney of type 2 diabetes mellitus (T2DM). Collectively, we demonstrated the potential protection of PGE1 on insulin resistance in renal tubules via autophagy-dependent FGF21 pathway in preventing the progression of DN.</description><subject>13/51</subject><subject>13/95</subject><subject>14/19</subject><subject>14/35</subject><subject>692/163/2743/137/138</subject><subject>692/4022/1585/104/1586</subject><subject>82/80</subject><subject>AKT protein</subject><subject>Autophagy</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Diabetes mellitus (non-insulin dependent)</subject><subject>Diabetic nephropathy</subject><subject>Epithelial cells</subject><subject>Fibroblast growth factors</subject><subject>Glucose</subject><subject>Glucose transporter</subject><subject>Humanities and Social Sciences</subject><subject>Immunohistochemistry</subject><subject>Insulin</subject><subject>Insulin receptor substrate 1</subject><subject>Insulin resistance</subject><subject>multidisciplinary</subject><subject>Nephropathy</subject><subject>Palmitic acid</subject><subject>Phagocytosis</subject><subject>Phosphorylation</subject><subject>Prostaglandin E1</subject><subject>Renal function</subject><subject>Renal tubules</subject><subject>Rodents</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Serine</subject><subject>siRNA</subject><subject>Western blotting</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kU9LHDEYh0NpqWL9Aj2UgBcvY_N_JhdBxN0KQntozyHJZHYis8mYzCjz7c12VbZCc0ngffK878sPgK8YXWBEm--ZYS6bCuG6wg0jdUU-gGOCGK8IJeTjwfsInOZ8j8rhRDIsP4MjIinGokHHoLsNvTd-8jHA2EEf8jz4AJPLPk86WAfNAn-tbzB89BrqeYpjrzdL1brRhdaFCa7WK4LhqKf-SS9FAFuvjZu8hcGNfYq7yvIFfOr0kN3py30C_qxufl__qO5-rm-vr-4qy2o2VaJFiOhaW4GIQRJxJ21XU8oNN0xrLRwimFnRCSOlsa1xLee8FoRRxAgW9ARc7r3jbLautWXApAc1Jr_VaVFRe_VvJfhebeKj4jVvarITnL8IUnyYXZ7U1mfrhkEHF-essGwkF0hQUtCzd-h9nFMo6xVKUoYFanChyJ6yKeacXPc2DEZql6TaJ6lKkupvkmqn_na4xtuX19wKQPdALqWwcemg9_-1z8tnqXc</recordid><startdate>20180108</startdate><enddate>20180108</enddate><creator>Wei, Wei</creator><creator>An, Xing-Rong</creator><creator>Jin, Shi-Jie</creator><creator>Li, Xiao-Xue</creator><creator>Xu, Ming</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20180108</creationdate><title>Inhibition of insulin resistance by PGE1 via autophagy-dependent FGF21 pathway in diabetic nephropathy</title><author>Wei, Wei ; 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Alprostadil (Prostaglandin E1, PGE1) had protective effects on renal function. However, it is unknown whether PGE1 inhibited insulin resistance in renal tubule epithelial cells via autophagy, which plays a protective role in DN against insulin resistance. Insulin resistance was induced by palmitic acid (PA) in human HK-2 cells, shown as the decrease of insulin-stimulated AKT phosphorylation, glucose transporter-4 (GLUT4), glucose uptake and enhanced phosphorylation of insulin receptor substrate 1(IRS-1) at site serine 307 (pIRS-1ser307) and downregulated expression of IRS-1. Along with less abundance of p62, autophagy markers LC3B and Beclin-1 significantly increased in HK-2 cells exposed to PA. Such abnormal changes were significantly reversed by PGE1, which mimicked the role of autophagy gene 7 small interfering RNA (ATG7 siRNA). Furthermore, PGE1 promoted the protein expression of autophagy-related fibroblast growth factor-21 (FGF21), which alleviated insulin resistance. Results from western blotting and immunohistochemistry indicated that PGE1 remarkably restored autophagy, insulin resistance and the FGF21 expression in rat kidney of type 2 diabetes mellitus (T2DM). Collectively, we demonstrated the potential protection of PGE1 on insulin resistance in renal tubules via autophagy-dependent FGF21 pathway in preventing the progression of DN.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>29311680</pmid><doi>10.1038/s41598-017-18427-2</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 13/51 13/95 14/19 14/35 692/163/2743/137/138 692/4022/1585/104/1586 82/80 AKT protein Autophagy Diabetes Diabetes mellitus Diabetes mellitus (non-insulin dependent) Diabetic nephropathy Epithelial cells Fibroblast growth factors Glucose Glucose transporter Humanities and Social Sciences Immunohistochemistry Insulin Insulin receptor substrate 1 Insulin resistance multidisciplinary Nephropathy Palmitic acid Phagocytosis Phosphorylation Prostaglandin E1 Renal function Renal tubules Rodents Science Science (multidisciplinary) Serine siRNA Western blotting |
| title | Inhibition of insulin resistance by PGE1 via autophagy-dependent FGF21 pathway in diabetic nephropathy |
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