Novel Polysaccharide H-1-2 from Pseudostellaria Heterophylla Alleviates Type 2 Diabetes Mellitus
Abstract Background/Aims: To investigate the potential therapeutic effect of novel polysaccharide H-1-2 from pseudostellaria heterophylla against type 2 Diabetes Mellitus (T2DM) and elucidate the underling molecular mechanisms. Methods: Relative expression of HIF1α and Sirt1 in T2DM patients was det...
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| Veröffentlicht in: | Cellular physiology and biochemistry 2018-01, Vol.49 (3), p.1037-1047 |
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| creator | Fang, Zhao-hui Duan, Xian-chun Zhao, Jin-dong Wu, Yuan-jie Liu, Meng-meng |
| description | Abstract
Background/Aims: To investigate the potential therapeutic effect of novel polysaccharide H-1-2 from pseudostellaria heterophylla against type 2 Diabetes Mellitus (T2DM) and elucidate the underling molecular mechanisms. Methods: Relative expression of HIF1α and Sirt1 in T2DM patients was determined via real-time PCR. The direct binding of HIF1α on Sirt1 promoter was validated by ChIP assay. The inhibitory regulation of Sirt1 by HIF1α was analyzed using luciferase reporter assay. The endogenous protein of HIF1α and Sirt1 in response to H-1-2 treatment was quantified by western blotting. The blood glucose, secreted insulin and serous lipid profiles were measured with ELISA kits. Results: We consolidated that HIF1α and Sirt1 was dysregulated in T2DM patients and subjected to H-1-2 modulation. H-1-2 significantly inhibited hypoxia and up-regulated Sirt1 expression in EndoC-βH1 cells. Accordingly, H-1-2 enhanced glucose-stimulation insulin secretion and improved blood glucose and lipid profiles in T2DM cells, and elevated the glucose and insulin tolerance simultaneously. Furthermore, we demonstrated that H-1-2 alleviated T2DM via inhibition of hypoxia and up-regulation of Sirt1 in isolated pancreatic β-cells from T2DM rats. Conclusion: Our data unambiguously demonstrated H-1-2 administration alleviated T2DM by enhancing Sirt1 expression through inhibition of hypoxia. |
| doi_str_mv | 10.1159/000493284 |
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Background/Aims: To investigate the potential therapeutic effect of novel polysaccharide H-1-2 from pseudostellaria heterophylla against type 2 Diabetes Mellitus (T2DM) and elucidate the underling molecular mechanisms. Methods: Relative expression of HIF1α and Sirt1 in T2DM patients was determined via real-time PCR. The direct binding of HIF1α on Sirt1 promoter was validated by ChIP assay. The inhibitory regulation of Sirt1 by HIF1α was analyzed using luciferase reporter assay. The endogenous protein of HIF1α and Sirt1 in response to H-1-2 treatment was quantified by western blotting. The blood glucose, secreted insulin and serous lipid profiles were measured with ELISA kits. Results: We consolidated that HIF1α and Sirt1 was dysregulated in T2DM patients and subjected to H-1-2 modulation. H-1-2 significantly inhibited hypoxia and up-regulated Sirt1 expression in EndoC-βH1 cells. Accordingly, H-1-2 enhanced glucose-stimulation insulin secretion and improved blood glucose and lipid profiles in T2DM cells, and elevated the glucose and insulin tolerance simultaneously. Furthermore, we demonstrated that H-1-2 alleviated T2DM via inhibition of hypoxia and up-regulation of Sirt1 in isolated pancreatic β-cells from T2DM rats. Conclusion: Our data unambiguously demonstrated H-1-2 administration alleviated T2DM by enhancing Sirt1 expression through inhibition of hypoxia.</description><identifier>ISSN: 1015-8987</identifier><identifier>EISSN: 1421-9778</identifier><identifier>DOI: 10.1159/000493284</identifier><identifier>PMID: 30196291</identifier><language>eng</language><publisher>Basel, Switzerland: S. Karger AG</publisher><subject>Animals ; Autophagy ; Blood Glucose - analysis ; Caryophyllaceae - metabolism ; Cell cycle ; Cell Line ; Chinese medicine ; Cobalt - pharmacology ; Deoxyribonucleic acid ; Diabetes ; Diabetes Mellitus, Type 2 - metabolism ; Diabetes Mellitus, Type 2 - pathology ; Diabetic retinopathy ; Disease Models, Animal ; DNA ; Female ; Glucose ; Glucose - pharmacology ; H-1-2 ; Humans ; Hypoxia ; Hypoxia-Inducible Factor 1, alpha Subunit - genetics ; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism ; Insulin ; Insulin - metabolism ; Insulin resistance ; Insulin-Secreting Cells - cytology ; Insulin-Secreting Cells - metabolism ; Kidneys ; Male ; MicroRNAs - genetics ; MicroRNAs - metabolism ; Original Paper ; Polysaccharides - metabolism ; Polysaccharides - pharmacology ; Promoter Regions, Genetic ; Rats ; Sirt1 ; Sirtuin 1 - metabolism ; T2DM ; Up-Regulation - drug effects</subject><ispartof>Cellular physiology and biochemistry, 2018-01, Vol.49 (3), p.1037-1047</ispartof><rights>2018 The Author(s). Published by S. Karger AG, Basel</rights><rights>2018 The Author(s). Published by S. Karger AG, Basel.</rights><rights>2018 The Author(s). Published by S. Karger AG, Basel . Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the associated terms available at: https://uk.sagepub.com/en-gb/eur/reusing-open-access-and-sage-choice-content</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c501t-6c2b4457dd30ca3c397c554c68a3d4b3bf201e5b670128b89d1dafc86253d7853</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,860,2096,27612,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30196291$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fang, Zhao-hui </creatorcontrib><creatorcontrib>Duan, Xian-chun</creatorcontrib><creatorcontrib>Zhao, Jin-dong</creatorcontrib><creatorcontrib>Wu, Yuan-jie</creatorcontrib><creatorcontrib>Liu, Meng-meng</creatorcontrib><title>Novel Polysaccharide H-1-2 from Pseudostellaria Heterophylla Alleviates Type 2 Diabetes Mellitus</title><title>Cellular physiology and biochemistry</title><addtitle>Cell Physiol Biochem</addtitle><description>Abstract
Background/Aims: To investigate the potential therapeutic effect of novel polysaccharide H-1-2 from pseudostellaria heterophylla against type 2 Diabetes Mellitus (T2DM) and elucidate the underling molecular mechanisms. Methods: Relative expression of HIF1α and Sirt1 in T2DM patients was determined via real-time PCR. The direct binding of HIF1α on Sirt1 promoter was validated by ChIP assay. The inhibitory regulation of Sirt1 by HIF1α was analyzed using luciferase reporter assay. The endogenous protein of HIF1α and Sirt1 in response to H-1-2 treatment was quantified by western blotting. The blood glucose, secreted insulin and serous lipid profiles were measured with ELISA kits. Results: We consolidated that HIF1α and Sirt1 was dysregulated in T2DM patients and subjected to H-1-2 modulation. H-1-2 significantly inhibited hypoxia and up-regulated Sirt1 expression in EndoC-βH1 cells. Accordingly, H-1-2 enhanced glucose-stimulation insulin secretion and improved blood glucose and lipid profiles in T2DM cells, and elevated the glucose and insulin tolerance simultaneously. Furthermore, we demonstrated that H-1-2 alleviated T2DM via inhibition of hypoxia and up-regulation of Sirt1 in isolated pancreatic β-cells from T2DM rats. Conclusion: Our data unambiguously demonstrated H-1-2 administration alleviated T2DM by enhancing Sirt1 expression through inhibition of hypoxia.</description><subject>Animals</subject><subject>Autophagy</subject><subject>Blood Glucose - analysis</subject><subject>Caryophyllaceae - metabolism</subject><subject>Cell cycle</subject><subject>Cell Line</subject><subject>Chinese medicine</subject><subject>Cobalt - pharmacology</subject><subject>Deoxyribonucleic acid</subject><subject>Diabetes</subject><subject>Diabetes Mellitus, Type 2 - metabolism</subject><subject>Diabetes Mellitus, Type 2 - pathology</subject><subject>Diabetic retinopathy</subject><subject>Disease Models, Animal</subject><subject>DNA</subject><subject>Female</subject><subject>Glucose</subject><subject>Glucose - pharmacology</subject><subject>H-1-2</subject><subject>Humans</subject><subject>Hypoxia</subject><subject>Hypoxia-Inducible Factor 1, alpha Subunit - genetics</subject><subject>Hypoxia-Inducible Factor 1, alpha Subunit - metabolism</subject><subject>Insulin</subject><subject>Insulin - metabolism</subject><subject>Insulin resistance</subject><subject>Insulin-Secreting Cells - cytology</subject><subject>Insulin-Secreting Cells - metabolism</subject><subject>Kidneys</subject><subject>Male</subject><subject>MicroRNAs - genetics</subject><subject>MicroRNAs - metabolism</subject><subject>Original Paper</subject><subject>Polysaccharides - metabolism</subject><subject>Polysaccharides - pharmacology</subject><subject>Promoter Regions, Genetic</subject><subject>Rats</subject><subject>Sirt1</subject><subject>Sirtuin 1 - metabolism</subject><subject>T2DM</subject><subject>Up-Regulation - drug effects</subject><issn>1015-8987</issn><issn>1421-9778</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>M--</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNpdkTtPHDEUha0IFAhJQY-QpTRJMcTvR4mAZJEIoSC18dh3YJZZvLFnkPbfx5vdbEFlH_u759r3IHRMyRml0n4jhAjLmRHv0CEVjDZWa7NX94TKxlijD9CHUuakSm3Ze3TACbWKWXqIHm7TKwz4Lg2r4kN48rmPgGcNbRjuclrguwJTTGWEYah3Hs9ghJyWT6uq8fkwwGvvRyj4frUEzPBl71tY65-1oB-n8hHtd34o8Gm7HqHf36_uL2bNza8f1xfnN02QhI6NCqwVQuoYOQmeB251kFIEZTyPouVtxwgF2SpNKDOtsZFG3wWjmORRG8mP0PXGNyY_d8vcL3xeueR79-8g5Ufn89iHAVzHQ2CWEQlRCFFbKRVbCx6IspZoqF5fNl7LnP5MUEa36EtYT-AF0lQcq4O1jCvGK_r5DTpPU36pP60U1dRKI1Slvm6okFMpGbrdAylx6wjdLsLKnm4dp3YBcUf-z6wCJxvg2edHyDtgW_8XkMqc7Q</recordid><startdate>20180101</startdate><enddate>20180101</enddate><creator>Fang, Zhao-hui </creator><creator>Duan, Xian-chun</creator><creator>Zhao, Jin-dong</creator><creator>Wu, Yuan-jie</creator><creator>Liu, Meng-meng</creator><general>S. Karger AG</general><general>Cell Physiol Biochem Press GmbH & Co KG</general><scope>M--</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>DOA</scope></search><sort><creationdate>20180101</creationdate><title>Novel Polysaccharide H-1-2 from Pseudostellaria Heterophylla Alleviates Type 2 Diabetes Mellitus</title><author>Fang, Zhao-hui ; Duan, Xian-chun ; Zhao, Jin-dong ; Wu, Yuan-jie ; Liu, Meng-meng</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c501t-6c2b4457dd30ca3c397c554c68a3d4b3bf201e5b670128b89d1dafc86253d7853</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Animals</topic><topic>Autophagy</topic><topic>Blood Glucose - analysis</topic><topic>Caryophyllaceae - metabolism</topic><topic>Cell cycle</topic><topic>Cell Line</topic><topic>Chinese medicine</topic><topic>Cobalt - pharmacology</topic><topic>Deoxyribonucleic acid</topic><topic>Diabetes</topic><topic>Diabetes Mellitus, Type 2 - metabolism</topic><topic>Diabetes Mellitus, Type 2 - pathology</topic><topic>Diabetic retinopathy</topic><topic>Disease Models, Animal</topic><topic>DNA</topic><topic>Female</topic><topic>Glucose</topic><topic>Glucose - pharmacology</topic><topic>H-1-2</topic><topic>Humans</topic><topic>Hypoxia</topic><topic>Hypoxia-Inducible Factor 1, alpha Subunit - genetics</topic><topic>Hypoxia-Inducible Factor 1, alpha Subunit - metabolism</topic><topic>Insulin</topic><topic>Insulin - metabolism</topic><topic>Insulin resistance</topic><topic>Insulin-Secreting Cells - cytology</topic><topic>Insulin-Secreting Cells - metabolism</topic><topic>Kidneys</topic><topic>Male</topic><topic>MicroRNAs - genetics</topic><topic>MicroRNAs - metabolism</topic><topic>Original Paper</topic><topic>Polysaccharides - metabolism</topic><topic>Polysaccharides - pharmacology</topic><topic>Promoter Regions, Genetic</topic><topic>Rats</topic><topic>Sirt1</topic><topic>Sirtuin 1 - metabolism</topic><topic>T2DM</topic><topic>Up-Regulation - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fang, Zhao-hui </creatorcontrib><creatorcontrib>Duan, Xian-chun</creatorcontrib><creatorcontrib>Zhao, Jin-dong</creatorcontrib><creatorcontrib>Wu, Yuan-jie</creatorcontrib><creatorcontrib>Liu, Meng-meng</creatorcontrib><collection>Karger Open Access Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>ProQuest Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Cellular physiology and biochemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fang, Zhao-hui </au><au>Duan, Xian-chun</au><au>Zhao, Jin-dong</au><au>Wu, Yuan-jie</au><au>Liu, Meng-meng</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Novel Polysaccharide H-1-2 from Pseudostellaria Heterophylla Alleviates Type 2 Diabetes Mellitus</atitle><jtitle>Cellular physiology and biochemistry</jtitle><addtitle>Cell Physiol Biochem</addtitle><date>2018-01-01</date><risdate>2018</risdate><volume>49</volume><issue>3</issue><spage>1037</spage><epage>1047</epage><pages>1037-1047</pages><issn>1015-8987</issn><eissn>1421-9778</eissn><abstract>Abstract
Background/Aims: To investigate the potential therapeutic effect of novel polysaccharide H-1-2 from pseudostellaria heterophylla against type 2 Diabetes Mellitus (T2DM) and elucidate the underling molecular mechanisms. Methods: Relative expression of HIF1α and Sirt1 in T2DM patients was determined via real-time PCR. The direct binding of HIF1α on Sirt1 promoter was validated by ChIP assay. The inhibitory regulation of Sirt1 by HIF1α was analyzed using luciferase reporter assay. The endogenous protein of HIF1α and Sirt1 in response to H-1-2 treatment was quantified by western blotting. The blood glucose, secreted insulin and serous lipid profiles were measured with ELISA kits. Results: We consolidated that HIF1α and Sirt1 was dysregulated in T2DM patients and subjected to H-1-2 modulation. H-1-2 significantly inhibited hypoxia and up-regulated Sirt1 expression in EndoC-βH1 cells. Accordingly, H-1-2 enhanced glucose-stimulation insulin secretion and improved blood glucose and lipid profiles in T2DM cells, and elevated the glucose and insulin tolerance simultaneously. Furthermore, we demonstrated that H-1-2 alleviated T2DM via inhibition of hypoxia and up-regulation of Sirt1 in isolated pancreatic β-cells from T2DM rats. Conclusion: Our data unambiguously demonstrated H-1-2 administration alleviated T2DM by enhancing Sirt1 expression through inhibition of hypoxia.</abstract><cop>Basel, Switzerland</cop><pub>S. Karger AG</pub><pmid>30196291</pmid><doi>10.1159/000493284</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Autophagy Blood Glucose - analysis Caryophyllaceae - metabolism Cell cycle Cell Line Chinese medicine Cobalt - pharmacology Deoxyribonucleic acid Diabetes Diabetes Mellitus, Type 2 - metabolism Diabetes Mellitus, Type 2 - pathology Diabetic retinopathy Disease Models, Animal DNA Female Glucose Glucose - pharmacology H-1-2 Humans Hypoxia Hypoxia-Inducible Factor 1, alpha Subunit - genetics Hypoxia-Inducible Factor 1, alpha Subunit - metabolism Insulin Insulin - metabolism Insulin resistance Insulin-Secreting Cells - cytology Insulin-Secreting Cells - metabolism Kidneys Male MicroRNAs - genetics MicroRNAs - metabolism Original Paper Polysaccharides - metabolism Polysaccharides - pharmacology Promoter Regions, Genetic Rats Sirt1 Sirtuin 1 - metabolism T2DM Up-Regulation - drug effects |
| title | Novel Polysaccharide H-1-2 from Pseudostellaria Heterophylla Alleviates Type 2 Diabetes Mellitus |
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