Amorphous solid dispersion of Berberine mitigates apoptosis via iPLA 2 β/Cardiolipin/Opa1 pathway in db/db mice and in Palmitate-treated MIN6 β-cells
: Berberine (BBR) improves beta-cell function in Type 2 diabetes (T2D) because of its anti-apoptotic activity, and our laboratory developed a new preparation named Huang-Gui Solid Dispersion (HGSD) to improve the oral bioavailability of BBR. However, the mechanism by which BBR inhibits beta-cell apo...
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| Veröffentlicht in: | International journal of biological sciences 2019, Vol.15 (7), p.1533-1545 |
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| creator | Li, Junnan Du, Hongwei Zhang, Meishuang Zhang, Zhi Teng, Fei Zhao, Yali Zhang, Wenyou Yu, Yang Feng, Linjing Cui, Xinming Zhang, Ming Lu, Tzongshi Guan, Fengying Chen, Li |
| description | : Berberine (BBR) improves beta-cell function in Type 2 diabetes (T2D) because of its anti-apoptotic activity, and our laboratory developed a new preparation named Huang-Gui Solid Dispersion (HGSD) to improve the oral bioavailability of BBR. However, the mechanism by which BBR inhibits beta-cell apoptosis is unclear. We hypothesized that the Group VIA Ca
-Independent Phospholipase A
(iPLA
β)/Cardiolipin(CL)/Opa1 signaling pathway could exert a protective role in T2D by regulating beta-cell apoptosis and that HGSD could inhibit β-cell apoptosis through iPLA
β/CL/Opa1 upregulation.
: We examined how iPLA
β and BBR regulated apoptosis and insulin secretion through CL/Opa1
and
. In
studies, we developed Palmitate(PA)-induced apoptotic cell death model in mouse insulinoma cells (MIN6). iPLA
β overexpression and silencing technology were used to examine how the iPLA
β/CL/Opa1 interaction may play an important role in BBR treatment. In
studies, db/db mice were used as a diabetic animal model. The pancreatic islet function and morphology, beta-cell apoptosis and mitochondrial injury were examined to explore the effects of HGSD. The expression of iPLA
β/CL/Opa1 was measured to explore whether the signaling pathway was damaged in T2D and was involved in HGSD treatment.
: The overexpression of iPLA
β and BBR treatment significantly attenuated Palmitate- induced mitochondrial injury and apoptotic death compared with Palmitate-treated MIN6 cell. In addition, iPLA
β silencing could simultaneously partly abolish the anti-apoptotic effect of BBR and decrease CL/Opa1 signaling in MIN6 cells. Moreover, HGSD treatment significantly decreased beta-cell apoptosis and resulted in the upregulation of iPLA
β/CL/Opa1 compared to those of the db/db mice.
: The results indicated that the regulation of iPLA
β/CL/Opa1 by HGSD may prevent beta-cell apoptosis and may improve islet beta-cell function in Type 2 diabetic mice and in palmitate-treated MIN6 cells. |
| doi_str_mv | 10.7150/ijbs.32020 |
| format | Article |
| fullrecord | <record><control><sourceid>pubmed_cross</sourceid><recordid>TN_cdi_crossref_primary_10_7150_ijbs_32020</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>31337982</sourcerecordid><originalsourceid>FETCH-LOGICAL-c992-e274dd5c29572e23b134bc02a53216c867b6b22beb44ecddfac450e1927751203</originalsourceid><addsrcrecordid>eNpNkEtOwzAURS0EouUzYQHIY6Q09nO-w1LxqVRoB51H_oW6SmPLTkFdCftgIayJlAJidJ-ejs7gIHRFySinKYnNWoQRAwLkCA1pkpQRQFEc_7sH6CyENSEsSwtyigaMMpaXBQzR-3hjvVvZbcDBNkZhZYLTPhjbYlvjW-2F9qbVeGM688I7HTB31nU2mIBfDcdmMRtjwJ8f8YR7ZXqHM208d5xix7vVG99h02IlYiV6h9SYt2r_WfCmV_bCqPO6H4Wfps9Z74mkbppwgU5q3gR9-bPnaHl_t5w8RrP5w3QynkWyLCHSkCdKpRLKNAcNTFCWCEmApwxoJossF5kAEFokiZZK1VwmKdG0hDxPKRB2jm4OWultCF7XlfNmw_2uoqTax632cavvuD18fYDdVmy0-kN_a7IvfIp3xg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Amorphous solid dispersion of Berberine mitigates apoptosis via iPLA 2 β/Cardiolipin/Opa1 pathway in db/db mice and in Palmitate-treated MIN6 β-cells</title><source>MEDLINE</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>PubMed Central Open Access</source><creator>Li, Junnan ; Du, Hongwei ; Zhang, Meishuang ; Zhang, Zhi ; Teng, Fei ; Zhao, Yali ; Zhang, Wenyou ; Yu, Yang ; Feng, Linjing ; Cui, Xinming ; Zhang, Ming ; Lu, Tzongshi ; Guan, Fengying ; Chen, Li</creator><creatorcontrib>Li, Junnan ; Du, Hongwei ; Zhang, Meishuang ; Zhang, Zhi ; Teng, Fei ; Zhao, Yali ; Zhang, Wenyou ; Yu, Yang ; Feng, Linjing ; Cui, Xinming ; Zhang, Ming ; Lu, Tzongshi ; Guan, Fengying ; Chen, Li</creatorcontrib><description>: Berberine (BBR) improves beta-cell function in Type 2 diabetes (T2D) because of its anti-apoptotic activity, and our laboratory developed a new preparation named Huang-Gui Solid Dispersion (HGSD) to improve the oral bioavailability of BBR. However, the mechanism by which BBR inhibits beta-cell apoptosis is unclear. We hypothesized that the Group VIA Ca
-Independent Phospholipase A
(iPLA
β)/Cardiolipin(CL)/Opa1 signaling pathway could exert a protective role in T2D by regulating beta-cell apoptosis and that HGSD could inhibit β-cell apoptosis through iPLA
β/CL/Opa1 upregulation.
: We examined how iPLA
β and BBR regulated apoptosis and insulin secretion through CL/Opa1
and
. In
studies, we developed Palmitate(PA)-induced apoptotic cell death model in mouse insulinoma cells (MIN6). iPLA
β overexpression and silencing technology were used to examine how the iPLA
β/CL/Opa1 interaction may play an important role in BBR treatment. In
studies, db/db mice were used as a diabetic animal model. The pancreatic islet function and morphology, beta-cell apoptosis and mitochondrial injury were examined to explore the effects of HGSD. The expression of iPLA
β/CL/Opa1 was measured to explore whether the signaling pathway was damaged in T2D and was involved in HGSD treatment.
: The overexpression of iPLA
β and BBR treatment significantly attenuated Palmitate- induced mitochondrial injury and apoptotic death compared with Palmitate-treated MIN6 cell. In addition, iPLA
β silencing could simultaneously partly abolish the anti-apoptotic effect of BBR and decrease CL/Opa1 signaling in MIN6 cells. Moreover, HGSD treatment significantly decreased beta-cell apoptosis and resulted in the upregulation of iPLA
β/CL/Opa1 compared to those of the db/db mice.
: The results indicated that the regulation of iPLA
β/CL/Opa1 by HGSD may prevent beta-cell apoptosis and may improve islet beta-cell function in Type 2 diabetic mice and in palmitate-treated MIN6 cells.</description><identifier>ISSN: 1449-2288</identifier><identifier>EISSN: 1449-2288</identifier><identifier>DOI: 10.7150/ijbs.32020</identifier><identifier>PMID: 31337982</identifier><language>eng</language><publisher>Australia</publisher><subject>Animals ; Apoptosis ; Berberine - pharmacology ; Cardiolipins - metabolism ; Cell Line ; Diabetes Mellitus, Experimental - metabolism ; Diabetes Mellitus, Type 2 - drug therapy ; Diabetes Mellitus, Type 2 - metabolism ; Gene Silencing ; Glucose Tolerance Test ; Group VI Phospholipases A2 - metabolism ; GTP Phosphohydrolases - metabolism ; Insulin - metabolism ; Insulin-Secreting Cells - metabolism ; Male ; Medicine, Chinese Traditional ; Membrane Potential, Mitochondrial ; Mice ; Mice, Inbred C57BL ; Mitochondria - metabolism ; Palmitates ; Signal Transduction</subject><ispartof>International journal of biological sciences, 2019, Vol.15 (7), p.1533-1545</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c992-e274dd5c29572e23b134bc02a53216c867b6b22beb44ecddfac450e1927751203</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,4010,27900,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31337982$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Junnan</creatorcontrib><creatorcontrib>Du, Hongwei</creatorcontrib><creatorcontrib>Zhang, Meishuang</creatorcontrib><creatorcontrib>Zhang, Zhi</creatorcontrib><creatorcontrib>Teng, Fei</creatorcontrib><creatorcontrib>Zhao, Yali</creatorcontrib><creatorcontrib>Zhang, Wenyou</creatorcontrib><creatorcontrib>Yu, Yang</creatorcontrib><creatorcontrib>Feng, Linjing</creatorcontrib><creatorcontrib>Cui, Xinming</creatorcontrib><creatorcontrib>Zhang, Ming</creatorcontrib><creatorcontrib>Lu, Tzongshi</creatorcontrib><creatorcontrib>Guan, Fengying</creatorcontrib><creatorcontrib>Chen, Li</creatorcontrib><title>Amorphous solid dispersion of Berberine mitigates apoptosis via iPLA 2 β/Cardiolipin/Opa1 pathway in db/db mice and in Palmitate-treated MIN6 β-cells</title><title>International journal of biological sciences</title><addtitle>Int J Biol Sci</addtitle><description>: Berberine (BBR) improves beta-cell function in Type 2 diabetes (T2D) because of its anti-apoptotic activity, and our laboratory developed a new preparation named Huang-Gui Solid Dispersion (HGSD) to improve the oral bioavailability of BBR. However, the mechanism by which BBR inhibits beta-cell apoptosis is unclear. We hypothesized that the Group VIA Ca
-Independent Phospholipase A
(iPLA
β)/Cardiolipin(CL)/Opa1 signaling pathway could exert a protective role in T2D by regulating beta-cell apoptosis and that HGSD could inhibit β-cell apoptosis through iPLA
β/CL/Opa1 upregulation.
: We examined how iPLA
β and BBR regulated apoptosis and insulin secretion through CL/Opa1
and
. In
studies, we developed Palmitate(PA)-induced apoptotic cell death model in mouse insulinoma cells (MIN6). iPLA
β overexpression and silencing technology were used to examine how the iPLA
β/CL/Opa1 interaction may play an important role in BBR treatment. In
studies, db/db mice were used as a diabetic animal model. The pancreatic islet function and morphology, beta-cell apoptosis and mitochondrial injury were examined to explore the effects of HGSD. The expression of iPLA
β/CL/Opa1 was measured to explore whether the signaling pathway was damaged in T2D and was involved in HGSD treatment.
: The overexpression of iPLA
β and BBR treatment significantly attenuated Palmitate- induced mitochondrial injury and apoptotic death compared with Palmitate-treated MIN6 cell. In addition, iPLA
β silencing could simultaneously partly abolish the anti-apoptotic effect of BBR and decrease CL/Opa1 signaling in MIN6 cells. Moreover, HGSD treatment significantly decreased beta-cell apoptosis and resulted in the upregulation of iPLA
β/CL/Opa1 compared to those of the db/db mice.
: The results indicated that the regulation of iPLA
β/CL/Opa1 by HGSD may prevent beta-cell apoptosis and may improve islet beta-cell function in Type 2 diabetic mice and in palmitate-treated MIN6 cells.</description><subject>Animals</subject><subject>Apoptosis</subject><subject>Berberine - pharmacology</subject><subject>Cardiolipins - metabolism</subject><subject>Cell Line</subject><subject>Diabetes Mellitus, Experimental - metabolism</subject><subject>Diabetes Mellitus, Type 2 - drug therapy</subject><subject>Diabetes Mellitus, Type 2 - metabolism</subject><subject>Gene Silencing</subject><subject>Glucose Tolerance Test</subject><subject>Group VI Phospholipases A2 - metabolism</subject><subject>GTP Phosphohydrolases - metabolism</subject><subject>Insulin - metabolism</subject><subject>Insulin-Secreting Cells - metabolism</subject><subject>Male</subject><subject>Medicine, Chinese Traditional</subject><subject>Membrane Potential, Mitochondrial</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mitochondria - metabolism</subject><subject>Palmitates</subject><subject>Signal Transduction</subject><issn>1449-2288</issn><issn>1449-2288</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpNkEtOwzAURS0EouUzYQHIY6Q09nO-w1LxqVRoB51H_oW6SmPLTkFdCftgIayJlAJidJ-ejs7gIHRFySinKYnNWoQRAwLkCA1pkpQRQFEc_7sH6CyENSEsSwtyigaMMpaXBQzR-3hjvVvZbcDBNkZhZYLTPhjbYlvjW-2F9qbVeGM688I7HTB31nU2mIBfDcdmMRtjwJ8f8YR7ZXqHM208d5xix7vVG99h02IlYiV6h9SYt2r_WfCmV_bCqPO6H4Wfps9Z74mkbppwgU5q3gR9-bPnaHl_t5w8RrP5w3QynkWyLCHSkCdKpRLKNAcNTFCWCEmApwxoJossF5kAEFokiZZK1VwmKdG0hDxPKRB2jm4OWultCF7XlfNmw_2uoqTax632cavvuD18fYDdVmy0-kN_a7IvfIp3xg</recordid><startdate>2019</startdate><enddate>2019</enddate><creator>Li, Junnan</creator><creator>Du, Hongwei</creator><creator>Zhang, Meishuang</creator><creator>Zhang, Zhi</creator><creator>Teng, Fei</creator><creator>Zhao, Yali</creator><creator>Zhang, Wenyou</creator><creator>Yu, Yang</creator><creator>Feng, Linjing</creator><creator>Cui, Xinming</creator><creator>Zhang, Ming</creator><creator>Lu, Tzongshi</creator><creator>Guan, Fengying</creator><creator>Chen, Li</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>2019</creationdate><title>Amorphous solid dispersion of Berberine mitigates apoptosis via iPLA 2 β/Cardiolipin/Opa1 pathway in db/db mice and in Palmitate-treated MIN6 β-cells</title><author>Li, Junnan ; Du, Hongwei ; Zhang, Meishuang ; Zhang, Zhi ; Teng, Fei ; Zhao, Yali ; Zhang, Wenyou ; Yu, Yang ; Feng, Linjing ; Cui, Xinming ; Zhang, Ming ; Lu, Tzongshi ; Guan, Fengying ; Chen, Li</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c992-e274dd5c29572e23b134bc02a53216c867b6b22beb44ecddfac450e1927751203</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Animals</topic><topic>Apoptosis</topic><topic>Berberine - pharmacology</topic><topic>Cardiolipins - metabolism</topic><topic>Cell Line</topic><topic>Diabetes Mellitus, Experimental - metabolism</topic><topic>Diabetes Mellitus, Type 2 - drug therapy</topic><topic>Diabetes Mellitus, Type 2 - metabolism</topic><topic>Gene Silencing</topic><topic>Glucose Tolerance Test</topic><topic>Group VI Phospholipases A2 - metabolism</topic><topic>GTP Phosphohydrolases - metabolism</topic><topic>Insulin - metabolism</topic><topic>Insulin-Secreting Cells - metabolism</topic><topic>Male</topic><topic>Medicine, Chinese Traditional</topic><topic>Membrane Potential, Mitochondrial</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mitochondria - metabolism</topic><topic>Palmitates</topic><topic>Signal Transduction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Junnan</creatorcontrib><creatorcontrib>Du, Hongwei</creatorcontrib><creatorcontrib>Zhang, Meishuang</creatorcontrib><creatorcontrib>Zhang, Zhi</creatorcontrib><creatorcontrib>Teng, Fei</creatorcontrib><creatorcontrib>Zhao, Yali</creatorcontrib><creatorcontrib>Zhang, Wenyou</creatorcontrib><creatorcontrib>Yu, Yang</creatorcontrib><creatorcontrib>Feng, Linjing</creatorcontrib><creatorcontrib>Cui, Xinming</creatorcontrib><creatorcontrib>Zhang, Ming</creatorcontrib><creatorcontrib>Lu, Tzongshi</creatorcontrib><creatorcontrib>Guan, Fengying</creatorcontrib><creatorcontrib>Chen, Li</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>International journal of biological sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Junnan</au><au>Du, Hongwei</au><au>Zhang, Meishuang</au><au>Zhang, Zhi</au><au>Teng, Fei</au><au>Zhao, Yali</au><au>Zhang, Wenyou</au><au>Yu, Yang</au><au>Feng, Linjing</au><au>Cui, Xinming</au><au>Zhang, Ming</au><au>Lu, Tzongshi</au><au>Guan, Fengying</au><au>Chen, Li</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Amorphous solid dispersion of Berberine mitigates apoptosis via iPLA 2 β/Cardiolipin/Opa1 pathway in db/db mice and in Palmitate-treated MIN6 β-cells</atitle><jtitle>International journal of biological sciences</jtitle><addtitle>Int J Biol Sci</addtitle><date>2019</date><risdate>2019</risdate><volume>15</volume><issue>7</issue><spage>1533</spage><epage>1545</epage><pages>1533-1545</pages><issn>1449-2288</issn><eissn>1449-2288</eissn><abstract>: Berberine (BBR) improves beta-cell function in Type 2 diabetes (T2D) because of its anti-apoptotic activity, and our laboratory developed a new preparation named Huang-Gui Solid Dispersion (HGSD) to improve the oral bioavailability of BBR. However, the mechanism by which BBR inhibits beta-cell apoptosis is unclear. We hypothesized that the Group VIA Ca
-Independent Phospholipase A
(iPLA
β)/Cardiolipin(CL)/Opa1 signaling pathway could exert a protective role in T2D by regulating beta-cell apoptosis and that HGSD could inhibit β-cell apoptosis through iPLA
β/CL/Opa1 upregulation.
: We examined how iPLA
β and BBR regulated apoptosis and insulin secretion through CL/Opa1
and
. In
studies, we developed Palmitate(PA)-induced apoptotic cell death model in mouse insulinoma cells (MIN6). iPLA
β overexpression and silencing technology were used to examine how the iPLA
β/CL/Opa1 interaction may play an important role in BBR treatment. In
studies, db/db mice were used as a diabetic animal model. The pancreatic islet function and morphology, beta-cell apoptosis and mitochondrial injury were examined to explore the effects of HGSD. The expression of iPLA
β/CL/Opa1 was measured to explore whether the signaling pathway was damaged in T2D and was involved in HGSD treatment.
: The overexpression of iPLA
β and BBR treatment significantly attenuated Palmitate- induced mitochondrial injury and apoptotic death compared with Palmitate-treated MIN6 cell. In addition, iPLA
β silencing could simultaneously partly abolish the anti-apoptotic effect of BBR and decrease CL/Opa1 signaling in MIN6 cells. Moreover, HGSD treatment significantly decreased beta-cell apoptosis and resulted in the upregulation of iPLA
β/CL/Opa1 compared to those of the db/db mice.
: The results indicated that the regulation of iPLA
β/CL/Opa1 by HGSD may prevent beta-cell apoptosis and may improve islet beta-cell function in Type 2 diabetic mice and in palmitate-treated MIN6 cells.</abstract><cop>Australia</cop><pmid>31337982</pmid><doi>10.7150/ijbs.32020</doi><tpages>13</tpages></addata></record> |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; PubMed Central; PubMed Central Open Access |
| subjects | Animals Apoptosis Berberine - pharmacology Cardiolipins - metabolism Cell Line Diabetes Mellitus, Experimental - metabolism Diabetes Mellitus, Type 2 - drug therapy Diabetes Mellitus, Type 2 - metabolism Gene Silencing Glucose Tolerance Test Group VI Phospholipases A2 - metabolism GTP Phosphohydrolases - metabolism Insulin - metabolism Insulin-Secreting Cells - metabolism Male Medicine, Chinese Traditional Membrane Potential, Mitochondrial Mice Mice, Inbred C57BL Mitochondria - metabolism Palmitates Signal Transduction |
| title | Amorphous solid dispersion of Berberine mitigates apoptosis via iPLA 2 β/Cardiolipin/Opa1 pathway in db/db mice and in Palmitate-treated MIN6 β-cells |
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