Effects of Agriophyllum squarrosum extracts on glucose metabolism in KKAy mice and the associated underlying mechanisms
Agriophyllum squarrosum (L.) Moq. is a traditional Mongol medicine commonly used in the treatment of diabetes. To examine the effects of Agriophyllum squarrosum extract (ASE) on glucose metabolism in type 2 diabetic KKAy mice, and to investigate the mechanisms underlying these effects. KKAy mice wer...
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| Veröffentlicht in: | Journal of ethnopharmacology 2019-09, Vol.241, p.112009-112009, Article 112009 |
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| creator | Saqier Bao, Shuyin Han, Shuying Ao, Wuliji |
| description | Agriophyllum squarrosum (L.) Moq. is a traditional Mongol medicine commonly used in the treatment of diabetes.
To examine the effects of Agriophyllum squarrosum extract (ASE) on glucose metabolism in type 2 diabetic KKAy mice, and to investigate the mechanisms underlying these effects.
KKAy mice were divided into a model control group (MCG), a low-dose Agriophyllum squarrosum extract group (LASEG), a medium-dose Agriophyllum squarrosum extract group (MASEG), a high-dose Agriophyllum squarrosum extract group (HASEG), and a metformin group (MEG). Syngeneic C57BL/6 mice were used as a normal control group (NCG). Drugs were administered to all mice by gavage for 8 weeks. Random blood glucose levels were measured in the mice at baseline and after 2, 4, and 8 weeks of treatment. Glucose tolerance was measured after 6 weeks of drug administration. After 8 weeks, glycated serum proteins (GSP) and advanced glycation end-products (AGEs) in the serum of all mice were measured. Sections of mouse liver tissues were used for periodic acid-Schiff staining (PAS) and the content of hepatic glycogen was determined. Immunohistochemistry was used to determine the effects of ASE on liver phospho-insulin receptor substrate 2 (P-IRS2) protein expression. Western blotting was used to quantify the protein expression levels of phosphatidylinositol 3-kinase (PI3K), AKT, phospho-AKT (S473) (P-AKT), glycogen synthase kinase 3β (GSK3β), and glucose transporters 4 (GLUT4), while PCR was used to quantify the mRNA expression levels of insulin receptor substrate 2 (IRS2), PI3K, AKT, GSK3β, and GLUT4.
ASE treatment decreased random blood glucose levels in type 2 diabetic KKAy mice; increased glucose tolerance; decreased serum GSP and AGEs content; increased glycogen synthesis in liver tissues; upregulated the protein expression levels of PI3K, AKT, GLUT4, and P-IRS2; downregulated the protein expression level of GSK3β in liver tissues; upregulated the mRNA expression levels of IRS2, PI3K, AKT, and GLUT4; and downregulated the mRNA expression level of GSK3β in liver tissues.
ASE treatment may increase glucose metabolism in KKAy mice and improve glucose tolerance. The underlying mechanisms of the beneficial effects of ASE may be associated with the increase of glycogen synthesis, the inhibition of AGEs production, the upregulation of IRS2, PI3K, AKT, and GLUT4 protein and mRNA expression, and the downregulation of GSK3β protein and mRNA expression.
Schematic representation of effects of Agrio |
| doi_str_mv | 10.1016/j.jep.2019.112009 |
| format | Article |
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To examine the effects of Agriophyllum squarrosum extract (ASE) on glucose metabolism in type 2 diabetic KKAy mice, and to investigate the mechanisms underlying these effects.
KKAy mice were divided into a model control group (MCG), a low-dose Agriophyllum squarrosum extract group (LASEG), a medium-dose Agriophyllum squarrosum extract group (MASEG), a high-dose Agriophyllum squarrosum extract group (HASEG), and a metformin group (MEG). Syngeneic C57BL/6 mice were used as a normal control group (NCG). Drugs were administered to all mice by gavage for 8 weeks. Random blood glucose levels were measured in the mice at baseline and after 2, 4, and 8 weeks of treatment. Glucose tolerance was measured after 6 weeks of drug administration. After 8 weeks, glycated serum proteins (GSP) and advanced glycation end-products (AGEs) in the serum of all mice were measured. Sections of mouse liver tissues were used for periodic acid-Schiff staining (PAS) and the content of hepatic glycogen was determined. Immunohistochemistry was used to determine the effects of ASE on liver phospho-insulin receptor substrate 2 (P-IRS2) protein expression. Western blotting was used to quantify the protein expression levels of phosphatidylinositol 3-kinase (PI3K), AKT, phospho-AKT (S473) (P-AKT), glycogen synthase kinase 3β (GSK3β), and glucose transporters 4 (GLUT4), while PCR was used to quantify the mRNA expression levels of insulin receptor substrate 2 (IRS2), PI3K, AKT, GSK3β, and GLUT4.
ASE treatment decreased random blood glucose levels in type 2 diabetic KKAy mice; increased glucose tolerance; decreased serum GSP and AGEs content; increased glycogen synthesis in liver tissues; upregulated the protein expression levels of PI3K, AKT, GLUT4, and P-IRS2; downregulated the protein expression level of GSK3β in liver tissues; upregulated the mRNA expression levels of IRS2, PI3K, AKT, and GLUT4; and downregulated the mRNA expression level of GSK3β in liver tissues.
ASE treatment may increase glucose metabolism in KKAy mice and improve glucose tolerance. The underlying mechanisms of the beneficial effects of ASE may be associated with the increase of glycogen synthesis, the inhibition of AGEs production, the upregulation of IRS2, PI3K, AKT, and GLUT4 protein and mRNA expression, and the downregulation of GSK3β protein and mRNA expression.
Schematic representation of effects of Agriophyllum squarrosum extracts on glucose metabolism in KKAy mice and the associated underlying mechanisms. [Display omitted]</description><identifier>ISSN: 0378-8741</identifier><identifier>EISSN: 1872-7573</identifier><identifier>DOI: 10.1016/j.jep.2019.112009</identifier><identifier>PMID: 31158442</identifier><language>eng</language><publisher>Ireland: Elsevier B.V</publisher><subject>Agriophyllum squarrosum extract ; Animals ; Blood Proteins - analysis ; Chenopodiaceae ; Diabetes Mellitus, Experimental - blood ; Diabetes Mellitus, Experimental - metabolism ; Disease Models, Animal ; Female ; Glucose - metabolism ; Glycation End Products, Advanced - blood ; Glycogen - metabolism ; Glycogen Synthase Kinase 3 beta - metabolism ; Insulin Receptor Substrate Proteins - metabolism ; Insulin Resistance ; KKAy mice ; Liver - drug effects ; Liver - metabolism ; Male ; Mechanism research ; Mice, Inbred C57BL ; Obesity - blood ; Obesity - metabolism ; Phosphatidylinositol 3-Kinases - metabolism ; Plant Extracts - pharmacology ; Proto-Oncogene Proteins c-akt - metabolism ; Type 2 diabetes mellitus</subject><ispartof>Journal of ethnopharmacology, 2019-09, Vol.241, p.112009-112009, Article 112009</ispartof><rights>2019 Elsevier B.V.</rights><rights>Copyright © 2019 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c353t-ad6af4d7ec73232378dc35f6799dc4541655a2c4453d39154214a76be3e2d0833</citedby><cites>FETCH-LOGICAL-c353t-ad6af4d7ec73232378dc35f6799dc4541655a2c4453d39154214a76be3e2d0833</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jep.2019.112009$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,777,781,3537,27905,27906,45976</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31158442$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Saqier</creatorcontrib><creatorcontrib>Bao, Shuyin</creatorcontrib><creatorcontrib>Han, Shuying</creatorcontrib><creatorcontrib>Ao, Wuliji</creatorcontrib><title>Effects of Agriophyllum squarrosum extracts on glucose metabolism in KKAy mice and the associated underlying mechanisms</title><title>Journal of ethnopharmacology</title><addtitle>J Ethnopharmacol</addtitle><description>Agriophyllum squarrosum (L.) Moq. is a traditional Mongol medicine commonly used in the treatment of diabetes.
To examine the effects of Agriophyllum squarrosum extract (ASE) on glucose metabolism in type 2 diabetic KKAy mice, and to investigate the mechanisms underlying these effects.
KKAy mice were divided into a model control group (MCG), a low-dose Agriophyllum squarrosum extract group (LASEG), a medium-dose Agriophyllum squarrosum extract group (MASEG), a high-dose Agriophyllum squarrosum extract group (HASEG), and a metformin group (MEG). Syngeneic C57BL/6 mice were used as a normal control group (NCG). Drugs were administered to all mice by gavage for 8 weeks. Random blood glucose levels were measured in the mice at baseline and after 2, 4, and 8 weeks of treatment. Glucose tolerance was measured after 6 weeks of drug administration. After 8 weeks, glycated serum proteins (GSP) and advanced glycation end-products (AGEs) in the serum of all mice were measured. Sections of mouse liver tissues were used for periodic acid-Schiff staining (PAS) and the content of hepatic glycogen was determined. Immunohistochemistry was used to determine the effects of ASE on liver phospho-insulin receptor substrate 2 (P-IRS2) protein expression. Western blotting was used to quantify the protein expression levels of phosphatidylinositol 3-kinase (PI3K), AKT, phospho-AKT (S473) (P-AKT), glycogen synthase kinase 3β (GSK3β), and glucose transporters 4 (GLUT4), while PCR was used to quantify the mRNA expression levels of insulin receptor substrate 2 (IRS2), PI3K, AKT, GSK3β, and GLUT4.
ASE treatment decreased random blood glucose levels in type 2 diabetic KKAy mice; increased glucose tolerance; decreased serum GSP and AGEs content; increased glycogen synthesis in liver tissues; upregulated the protein expression levels of PI3K, AKT, GLUT4, and P-IRS2; downregulated the protein expression level of GSK3β in liver tissues; upregulated the mRNA expression levels of IRS2, PI3K, AKT, and GLUT4; and downregulated the mRNA expression level of GSK3β in liver tissues.
ASE treatment may increase glucose metabolism in KKAy mice and improve glucose tolerance. The underlying mechanisms of the beneficial effects of ASE may be associated with the increase of glycogen synthesis, the inhibition of AGEs production, the upregulation of IRS2, PI3K, AKT, and GLUT4 protein and mRNA expression, and the downregulation of GSK3β protein and mRNA expression.
Schematic representation of effects of Agriophyllum squarrosum extracts on glucose metabolism in KKAy mice and the associated underlying mechanisms. [Display omitted]</description><subject>Agriophyllum squarrosum extract</subject><subject>Animals</subject><subject>Blood Proteins - analysis</subject><subject>Chenopodiaceae</subject><subject>Diabetes Mellitus, Experimental - blood</subject><subject>Diabetes Mellitus, Experimental - metabolism</subject><subject>Disease Models, Animal</subject><subject>Female</subject><subject>Glucose - metabolism</subject><subject>Glycation End Products, Advanced - blood</subject><subject>Glycogen - metabolism</subject><subject>Glycogen Synthase Kinase 3 beta - metabolism</subject><subject>Insulin Receptor Substrate Proteins - metabolism</subject><subject>Insulin Resistance</subject><subject>KKAy mice</subject><subject>Liver - drug effects</subject><subject>Liver - metabolism</subject><subject>Male</subject><subject>Mechanism research</subject><subject>Mice, Inbred C57BL</subject><subject>Obesity - blood</subject><subject>Obesity - metabolism</subject><subject>Phosphatidylinositol 3-Kinases - metabolism</subject><subject>Plant Extracts - pharmacology</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>Type 2 diabetes mellitus</subject><issn>0378-8741</issn><issn>1872-7573</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMtOwzAQRS0EgvL4ADbISzYpfsaJWFWIl0BiA2vLtSetqyQudgL07zEUWCIvxtKce6U5CJ1SMqWElher6QrWU0ZoPaWUEVLvoAmtFCuUVHwXTQhXVVEpQQ_QYUorQoiiguyjA06prIRgE_R-3TRgh4RDg2eL6MN6uWnbscPpdTQxhpS_8DFE8830eNGONiTAHQxmHlqfOux7_PAw2-DOW8Cmd3hY5plSsN4M4PDYO4jtxveLnLJL0-dQOkZ7jWkTnPzMI_Ryc_18dVc8Pt3eX80eC8slHwrjStMIp8AqzvJTlcuLplR17ayQgpZSGmaFkNzxmkrBqDCqnAMH5kjF-RE63_auY3gdIQ2688lC25oewpg0Y1ySkouyzijdojafnSI0eh19Z-JGU6K_fOuVzr71l2-99Z0zZz_147wD95f4FZyByy0A-cg3D1En66G34HzM3rUL_p_6T5jukYk</recordid><startdate>20190915</startdate><enddate>20190915</enddate><creator>Saqier</creator><creator>Bao, Shuyin</creator><creator>Han, Shuying</creator><creator>Ao, Wuliji</creator><general>Elsevier B.V</general><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>7X8</scope></search><sort><creationdate>20190915</creationdate><title>Effects of Agriophyllum squarrosum extracts on glucose metabolism in KKAy mice and the associated underlying mechanisms</title><author>Saqier ; Bao, Shuyin ; Han, Shuying ; Ao, Wuliji</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c353t-ad6af4d7ec73232378dc35f6799dc4541655a2c4453d39154214a76be3e2d0833</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Agriophyllum squarrosum extract</topic><topic>Animals</topic><topic>Blood Proteins - analysis</topic><topic>Chenopodiaceae</topic><topic>Diabetes Mellitus, Experimental - blood</topic><topic>Diabetes Mellitus, Experimental - metabolism</topic><topic>Disease Models, Animal</topic><topic>Female</topic><topic>Glucose - metabolism</topic><topic>Glycation End Products, Advanced - blood</topic><topic>Glycogen - metabolism</topic><topic>Glycogen Synthase Kinase 3 beta - metabolism</topic><topic>Insulin Receptor Substrate Proteins - metabolism</topic><topic>Insulin Resistance</topic><topic>KKAy mice</topic><topic>Liver - drug effects</topic><topic>Liver - metabolism</topic><topic>Male</topic><topic>Mechanism research</topic><topic>Mice, Inbred C57BL</topic><topic>Obesity - blood</topic><topic>Obesity - metabolism</topic><topic>Phosphatidylinositol 3-Kinases - metabolism</topic><topic>Plant Extracts - pharmacology</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>Type 2 diabetes mellitus</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Saqier</creatorcontrib><creatorcontrib>Bao, Shuyin</creatorcontrib><creatorcontrib>Han, Shuying</creatorcontrib><creatorcontrib>Ao, Wuliji</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of ethnopharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Saqier</au><au>Bao, Shuyin</au><au>Han, Shuying</au><au>Ao, Wuliji</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of Agriophyllum squarrosum extracts on glucose metabolism in KKAy mice and the associated underlying mechanisms</atitle><jtitle>Journal of ethnopharmacology</jtitle><addtitle>J Ethnopharmacol</addtitle><date>2019-09-15</date><risdate>2019</risdate><volume>241</volume><spage>112009</spage><epage>112009</epage><pages>112009-112009</pages><artnum>112009</artnum><issn>0378-8741</issn><eissn>1872-7573</eissn><abstract>Agriophyllum squarrosum (L.) Moq. is a traditional Mongol medicine commonly used in the treatment of diabetes.
To examine the effects of Agriophyllum squarrosum extract (ASE) on glucose metabolism in type 2 diabetic KKAy mice, and to investigate the mechanisms underlying these effects.
KKAy mice were divided into a model control group (MCG), a low-dose Agriophyllum squarrosum extract group (LASEG), a medium-dose Agriophyllum squarrosum extract group (MASEG), a high-dose Agriophyllum squarrosum extract group (HASEG), and a metformin group (MEG). Syngeneic C57BL/6 mice were used as a normal control group (NCG). Drugs were administered to all mice by gavage for 8 weeks. Random blood glucose levels were measured in the mice at baseline and after 2, 4, and 8 weeks of treatment. Glucose tolerance was measured after 6 weeks of drug administration. After 8 weeks, glycated serum proteins (GSP) and advanced glycation end-products (AGEs) in the serum of all mice were measured. Sections of mouse liver tissues were used for periodic acid-Schiff staining (PAS) and the content of hepatic glycogen was determined. Immunohistochemistry was used to determine the effects of ASE on liver phospho-insulin receptor substrate 2 (P-IRS2) protein expression. Western blotting was used to quantify the protein expression levels of phosphatidylinositol 3-kinase (PI3K), AKT, phospho-AKT (S473) (P-AKT), glycogen synthase kinase 3β (GSK3β), and glucose transporters 4 (GLUT4), while PCR was used to quantify the mRNA expression levels of insulin receptor substrate 2 (IRS2), PI3K, AKT, GSK3β, and GLUT4.
ASE treatment decreased random blood glucose levels in type 2 diabetic KKAy mice; increased glucose tolerance; decreased serum GSP and AGEs content; increased glycogen synthesis in liver tissues; upregulated the protein expression levels of PI3K, AKT, GLUT4, and P-IRS2; downregulated the protein expression level of GSK3β in liver tissues; upregulated the mRNA expression levels of IRS2, PI3K, AKT, and GLUT4; and downregulated the mRNA expression level of GSK3β in liver tissues.
ASE treatment may increase glucose metabolism in KKAy mice and improve glucose tolerance. The underlying mechanisms of the beneficial effects of ASE may be associated with the increase of glycogen synthesis, the inhibition of AGEs production, the upregulation of IRS2, PI3K, AKT, and GLUT4 protein and mRNA expression, and the downregulation of GSK3β protein and mRNA expression.
Schematic representation of effects of Agriophyllum squarrosum extracts on glucose metabolism in KKAy mice and the associated underlying mechanisms. [Display omitted]</abstract><cop>Ireland</cop><pub>Elsevier B.V</pub><pmid>31158442</pmid><doi>10.1016/j.jep.2019.112009</doi><tpages>1</tpages></addata></record> |
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| ispartof | Journal of ethnopharmacology, 2019-09, Vol.241, p.112009-112009, Article 112009 |
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| subjects | Agriophyllum squarrosum extract Animals Blood Proteins - analysis Chenopodiaceae Diabetes Mellitus, Experimental - blood Diabetes Mellitus, Experimental - metabolism Disease Models, Animal Female Glucose - metabolism Glycation End Products, Advanced - blood Glycogen - metabolism Glycogen Synthase Kinase 3 beta - metabolism Insulin Receptor Substrate Proteins - metabolism Insulin Resistance KKAy mice Liver - drug effects Liver - metabolism Male Mechanism research Mice, Inbred C57BL Obesity - blood Obesity - metabolism Phosphatidylinositol 3-Kinases - metabolism Plant Extracts - pharmacology Proto-Oncogene Proteins c-akt - metabolism Type 2 diabetes mellitus |
| title | Effects of Agriophyllum squarrosum extracts on glucose metabolism in KKAy mice and the associated underlying mechanisms |
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