169-OR: LC3+ Extracellular Vesicles (EVs) Are Associated with Altered ß-Cell Autophagy, Islet Inflammation, and Diabetes
Introduction: EVs, nanoparticles housing molecular cargo, change based on parent cell health and contribute to cell-cell communication. Yet, mechanisms governing changes and physiological significance of β cell EV cargo remain unclear. Autophagy is a critical intracellular degradation and recycling...
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| Veröffentlicht in: | Diabetes (New York, N.Y.) N.Y.), 2024-06, Vol.73, p.1 |
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| creator | Xu, Jerry Austin, Matthew Linnemann, Amelia K Sims, Emily K |
| description | Introduction: EVs, nanoparticles housing molecular cargo, change based on parent cell health and contribute to cell-cell communication. Yet, mechanisms governing changes and physiological significance of β cell EV cargo remain unclear. Autophagy is a critical intracellular degradation and recycling process to clear damaged cellular components. EV-autophagy crosstalk is an emerging area of interest with implications for both physiological and pathological states. We have described altered β cell autophagy associated with islet inflammation and type 1 diabetes (T1D). Based on this and reports of autophagy machinery such as LC3 in EVs from other systems, we hypothesized that changes in the LC3+ EV population could yield insight into β cell autophagy. Methods: Small EVs ( |
| doi_str_mv | 10.2337/db24-169-OR |
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| fullrecord | <record><control><sourceid>proquest</sourceid><recordid>TN_cdi_proquest_journals_3100300705</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3100300705</sourcerecordid><originalsourceid>FETCH-proquest_journals_31003007053</originalsourceid><addsrcrecordid>eNqNi11KAzEUhYMoOP48uYELvig2ejPRhvFtGEcsCIJI8a2kM7c2JZ3U3Aza1bgYN-aALkDOw-HwfUeIE4WXudbmqp3n11KNC_n0vCMyVehC6ty87ooMUeVSmcLsiwPmFSKOh2Ri-2vfwmOlL6D-TNE25H3vbYQpsWs8MZzVUz6HMhKUzKFxNlELHy4tofSJ4jC-v2Q13KDsU9gs7dt2BBP2lGDSLbxdr21yoRuB7Vq4c3ZOifhI7C2sZzr-60Nxel-_VA9yE8N7T5xmq9DHbkAzrRA1osEb_T_rB6QfURg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3100300705</pqid></control><display><type>article</type><title>169-OR: LC3+ Extracellular Vesicles (EVs) Are Associated with Altered ß-Cell Autophagy, Islet Inflammation, and Diabetes</title><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><creator>Xu, Jerry ; Austin, Matthew ; Linnemann, Amelia K ; Sims, Emily K</creator><creatorcontrib>Xu, Jerry ; Austin, Matthew ; Linnemann, Amelia K ; Sims, Emily K</creatorcontrib><description>Introduction: EVs, nanoparticles housing molecular cargo, change based on parent cell health and contribute to cell-cell communication. Yet, mechanisms governing changes and physiological significance of β cell EV cargo remain unclear. Autophagy is a critical intracellular degradation and recycling process to clear damaged cellular components. EV-autophagy crosstalk is an emerging area of interest with implications for both physiological and pathological states. We have described altered β cell autophagy associated with islet inflammation and type 1 diabetes (T1D). Based on this and reports of autophagy machinery such as LC3 in EVs from other systems, we hypothesized that changes in the LC3+ EV population could yield insight into β cell autophagy. Methods: Small EVs (<200nm) were isolated from INS-1 and EndoC β cells, islets, or plasma using tetraspanin (CD9, CD81, CD63) or LC3 antibody-based bead pulldown and quantified with flow cytometry. Results: We detected LC3 on the surface of EVs from β cells and normal islets. EV LC3 staining was also significantly increased by 24-hr treatment with 10 ng/mL IL-1β or 10μM caffeic acid phenethyl ester, a neutral sphingomyelinase-2 activator linked to regulation of EV subpopulations during inflammatory stress. Alternatively, LC3 staining was reduced in islet EVs from mice with β cell deletion of the critical autophagy enzyme ATG7, linking LC3+ EVs to autophagosome formation. LC3 pulldown specifically isolated β cell EVs and demonstrated the presence of proinsulin in LC3+ EVs. Finally, LC3 staining was significantly increased in plasma EVs of 20 children with new-onset T1D compared to age, sex, and BMI matched controls. Conclusion: LC3 is present on the surface of β cell EV membranes, and both β cell and circulating EV LC3 are impacted by defects in autophagy, islet inflammation, and T1D. Future studies will determine whether and how the population of LC3+ EVs participate in specific stages of autophagy or β cell pathophysiology.</description><identifier>ISSN: 0012-1797</identifier><identifier>EISSN: 1939-327X</identifier><identifier>DOI: 10.2337/db24-169-OR</identifier><language>eng</language><publisher>New York: American Diabetes Association</publisher><subject>Autophagy ; Beta cells ; Caffeic acid ; CD63 antigen ; CD81 antigen ; CD9 antigen ; Cell interactions ; Clonal deletion ; Diabetes ; Diabetes mellitus (insulin dependent) ; Flow cytometry ; Inflammation ; Insulin ; Intracellular signalling ; Nanoparticles ; Physiology ; Population studies ; Sphingomyelin phosphodiesterase</subject><ispartof>Diabetes (New York, N.Y.), 2024-06, Vol.73, p.1</ispartof><rights>Copyright American Diabetes Association Jun 2024</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,782,786,27931,27932</link.rule.ids></links><search><creatorcontrib>Xu, Jerry</creatorcontrib><creatorcontrib>Austin, Matthew</creatorcontrib><creatorcontrib>Linnemann, Amelia K</creatorcontrib><creatorcontrib>Sims, Emily K</creatorcontrib><title>169-OR: LC3+ Extracellular Vesicles (EVs) Are Associated with Altered ß-Cell Autophagy, Islet Inflammation, and Diabetes</title><title>Diabetes (New York, N.Y.)</title><description>Introduction: EVs, nanoparticles housing molecular cargo, change based on parent cell health and contribute to cell-cell communication. Yet, mechanisms governing changes and physiological significance of β cell EV cargo remain unclear. Autophagy is a critical intracellular degradation and recycling process to clear damaged cellular components. EV-autophagy crosstalk is an emerging area of interest with implications for both physiological and pathological states. We have described altered β cell autophagy associated with islet inflammation and type 1 diabetes (T1D). Based on this and reports of autophagy machinery such as LC3 in EVs from other systems, we hypothesized that changes in the LC3+ EV population could yield insight into β cell autophagy. Methods: Small EVs (<200nm) were isolated from INS-1 and EndoC β cells, islets, or plasma using tetraspanin (CD9, CD81, CD63) or LC3 antibody-based bead pulldown and quantified with flow cytometry. Results: We detected LC3 on the surface of EVs from β cells and normal islets. EV LC3 staining was also significantly increased by 24-hr treatment with 10 ng/mL IL-1β or 10μM caffeic acid phenethyl ester, a neutral sphingomyelinase-2 activator linked to regulation of EV subpopulations during inflammatory stress. Alternatively, LC3 staining was reduced in islet EVs from mice with β cell deletion of the critical autophagy enzyme ATG7, linking LC3+ EVs to autophagosome formation. LC3 pulldown specifically isolated β cell EVs and demonstrated the presence of proinsulin in LC3+ EVs. Finally, LC3 staining was significantly increased in plasma EVs of 20 children with new-onset T1D compared to age, sex, and BMI matched controls. Conclusion: LC3 is present on the surface of β cell EV membranes, and both β cell and circulating EV LC3 are impacted by defects in autophagy, islet inflammation, and T1D. Future studies will determine whether and how the population of LC3+ EVs participate in specific stages of autophagy or β cell pathophysiology.</description><subject>Autophagy</subject><subject>Beta cells</subject><subject>Caffeic acid</subject><subject>CD63 antigen</subject><subject>CD81 antigen</subject><subject>CD9 antigen</subject><subject>Cell interactions</subject><subject>Clonal deletion</subject><subject>Diabetes</subject><subject>Diabetes mellitus (insulin dependent)</subject><subject>Flow cytometry</subject><subject>Inflammation</subject><subject>Insulin</subject><subject>Intracellular signalling</subject><subject>Nanoparticles</subject><subject>Physiology</subject><subject>Population studies</subject><subject>Sphingomyelin phosphodiesterase</subject><issn>0012-1797</issn><issn>1939-327X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNqNi11KAzEUhYMoOP48uYELvig2ejPRhvFtGEcsCIJI8a2kM7c2JZ3U3Aza1bgYN-aALkDOw-HwfUeIE4WXudbmqp3n11KNC_n0vCMyVehC6ty87ooMUeVSmcLsiwPmFSKOh2Ri-2vfwmOlL6D-TNE25H3vbYQpsWs8MZzVUz6HMhKUzKFxNlELHy4tofSJ4jC-v2Q13KDsU9gs7dt2BBP2lGDSLbxdr21yoRuB7Vq4c3ZOifhI7C2sZzr-60Nxel-_VA9yE8N7T5xmq9DHbkAzrRA1osEb_T_rB6QfURg</recordid><startdate>20240601</startdate><enddate>20240601</enddate><creator>Xu, Jerry</creator><creator>Austin, Matthew</creator><creator>Linnemann, Amelia K</creator><creator>Sims, Emily K</creator><general>American Diabetes Association</general><scope>K9.</scope><scope>NAPCQ</scope></search><sort><creationdate>20240601</creationdate><title>169-OR: LC3+ Extracellular Vesicles (EVs) Are Associated with Altered ß-Cell Autophagy, Islet Inflammation, and Diabetes</title><author>Xu, Jerry ; Austin, Matthew ; Linnemann, Amelia K ; Sims, Emily K</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-proquest_journals_31003007053</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Autophagy</topic><topic>Beta cells</topic><topic>Caffeic acid</topic><topic>CD63 antigen</topic><topic>CD81 antigen</topic><topic>CD9 antigen</topic><topic>Cell interactions</topic><topic>Clonal deletion</topic><topic>Diabetes</topic><topic>Diabetes mellitus (insulin dependent)</topic><topic>Flow cytometry</topic><topic>Inflammation</topic><topic>Insulin</topic><topic>Intracellular signalling</topic><topic>Nanoparticles</topic><topic>Physiology</topic><topic>Population studies</topic><topic>Sphingomyelin phosphodiesterase</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Xu, Jerry</creatorcontrib><creatorcontrib>Austin, Matthew</creatorcontrib><creatorcontrib>Linnemann, Amelia K</creatorcontrib><creatorcontrib>Sims, Emily K</creatorcontrib><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><jtitle>Diabetes (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Xu, Jerry</au><au>Austin, Matthew</au><au>Linnemann, Amelia K</au><au>Sims, Emily K</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>169-OR: LC3+ Extracellular Vesicles (EVs) Are Associated with Altered ß-Cell Autophagy, Islet Inflammation, and Diabetes</atitle><jtitle>Diabetes (New York, N.Y.)</jtitle><date>2024-06-01</date><risdate>2024</risdate><volume>73</volume><spage>1</spage><pages>1-</pages><issn>0012-1797</issn><eissn>1939-327X</eissn><abstract>Introduction: EVs, nanoparticles housing molecular cargo, change based on parent cell health and contribute to cell-cell communication. Yet, mechanisms governing changes and physiological significance of β cell EV cargo remain unclear. Autophagy is a critical intracellular degradation and recycling process to clear damaged cellular components. EV-autophagy crosstalk is an emerging area of interest with implications for both physiological and pathological states. We have described altered β cell autophagy associated with islet inflammation and type 1 diabetes (T1D). Based on this and reports of autophagy machinery such as LC3 in EVs from other systems, we hypothesized that changes in the LC3+ EV population could yield insight into β cell autophagy. Methods: Small EVs (<200nm) were isolated from INS-1 and EndoC β cells, islets, or plasma using tetraspanin (CD9, CD81, CD63) or LC3 antibody-based bead pulldown and quantified with flow cytometry. Results: We detected LC3 on the surface of EVs from β cells and normal islets. EV LC3 staining was also significantly increased by 24-hr treatment with 10 ng/mL IL-1β or 10μM caffeic acid phenethyl ester, a neutral sphingomyelinase-2 activator linked to regulation of EV subpopulations during inflammatory stress. Alternatively, LC3 staining was reduced in islet EVs from mice with β cell deletion of the critical autophagy enzyme ATG7, linking LC3+ EVs to autophagosome formation. LC3 pulldown specifically isolated β cell EVs and demonstrated the presence of proinsulin in LC3+ EVs. Finally, LC3 staining was significantly increased in plasma EVs of 20 children with new-onset T1D compared to age, sex, and BMI matched controls. Conclusion: LC3 is present on the surface of β cell EV membranes, and both β cell and circulating EV LC3 are impacted by defects in autophagy, islet inflammation, and T1D. Future studies will determine whether and how the population of LC3+ EVs participate in specific stages of autophagy or β cell pathophysiology.</abstract><cop>New York</cop><pub>American Diabetes Association</pub><doi>10.2337/db24-169-OR</doi></addata></record> |
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| source | Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Autophagy Beta cells Caffeic acid CD63 antigen CD81 antigen CD9 antigen Cell interactions Clonal deletion Diabetes Diabetes mellitus (insulin dependent) Flow cytometry Inflammation Insulin Intracellular signalling Nanoparticles Physiology Population studies Sphingomyelin phosphodiesterase |
| title | 169-OR: LC3+ Extracellular Vesicles (EVs) Are Associated with Altered ß-Cell Autophagy, Islet Inflammation, and Diabetes |
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