The adhesion receptor GPR56 is activated by extracellular matrix collagen III to improve β-cell function

Aims G-protein coupled receptor 56 (GPR56) is the most abundant islet-expressed G-protein coupled receptor, suggesting a potential role in islet function. This study evaluated islet expression of GPR56 and its endogenous ligand collagen III, and their effects on β-cell function. Methods GPR56 and co...

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Veröffentlicht in:Cellular and molecular life sciences : CMLS 2018-11, Vol.75 (21), p.4007-4019
Hauptverfasser: Olaniru, Oladapo E., Pingitore, Attilio, Giera, Stefanie, Piao, Xianhua, Castañera González, Ramón, Jones, Peter M., Persaud, Shanta J.
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container_end_page 4019
container_issue 21
container_start_page 4007
container_title Cellular and molecular life sciences : CMLS
container_volume 75
creator Olaniru, Oladapo E.
Pingitore, Attilio
Giera, Stefanie
Piao, Xianhua
Castañera González, Ramón
Jones, Peter M.
Persaud, Shanta J.
description Aims G-protein coupled receptor 56 (GPR56) is the most abundant islet-expressed G-protein coupled receptor, suggesting a potential role in islet function. This study evaluated islet expression of GPR56 and its endogenous ligand collagen III, and their effects on β-cell function. Methods GPR56 and collagen III expression in mouse and human pancreas sections was determined by fluorescence immunohistochemistry. Effects of collagen III on β-cell proliferation, apoptosis, intracellular calcium ([Ca 2+ ] i ) and insulin secretion were determined by cellular BrdU incorporation, caspase 3/7 activities, microfluorimetry and radioimmunoassay, respectively. The role of GPR56 in islet vascularisation and innervation was evaluated by immunohistochemical staining for CD31 and TUJ1, respectively, in pancreases from wildtype (WT) and Gpr56 −/− mice, and the requirement of GPR56 for normal glucose homeostasis was determined by glucose tolerance tests in WT and Gpr56 −/− mice. Results Immunostaining of mouse and human pancreases revealed that GPR56 was expressed by islet β-cells while collagen III was confined to the peri-islet basement membrane and islet capillaries. Collagen III protected β-cells from cytokine-induced apoptosis, triggered increases in [Ca 2+ ] i and potentiated glucose-induced insulin secretion from WT islets but not from Gpr56 −/− islets. Deletion of GPR56 did not affect glucose-induced insulin secretion in vitro and it did not impair glucose tolerance in adult mice. GPR56 was not required for normal islet vascularisation or innervation. Conclusion We have demonstrated that collagen III improves islet function by increasing insulin secretion and protecting against apoptosis. Our data suggest that collagen III may be effective in optimising islet function to improve islet transplantation outcomes, and GPR56 may be a target for the treatment of type 2 diabetes.
doi_str_mv 10.1007/s00018-018-2846-4
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This study evaluated islet expression of GPR56 and its endogenous ligand collagen III, and their effects on β-cell function. Methods GPR56 and collagen III expression in mouse and human pancreas sections was determined by fluorescence immunohistochemistry. Effects of collagen III on β-cell proliferation, apoptosis, intracellular calcium ([Ca 2+ ] i ) and insulin secretion were determined by cellular BrdU incorporation, caspase 3/7 activities, microfluorimetry and radioimmunoassay, respectively. The role of GPR56 in islet vascularisation and innervation was evaluated by immunohistochemical staining for CD31 and TUJ1, respectively, in pancreases from wildtype (WT) and Gpr56 −/− mice, and the requirement of GPR56 for normal glucose homeostasis was determined by glucose tolerance tests in WT and Gpr56 −/− mice. Results Immunostaining of mouse and human pancreases revealed that GPR56 was expressed by islet β-cells while collagen III was confined to the peri-islet basement membrane and islet capillaries. Collagen III protected β-cells from cytokine-induced apoptosis, triggered increases in [Ca 2+ ] i and potentiated glucose-induced insulin secretion from WT islets but not from Gpr56 −/− islets. Deletion of GPR56 did not affect glucose-induced insulin secretion in vitro and it did not impair glucose tolerance in adult mice. GPR56 was not required for normal islet vascularisation or innervation. Conclusion We have demonstrated that collagen III improves islet function by increasing insulin secretion and protecting against apoptosis. Our data suggest that collagen III may be effective in optimising islet function to improve islet transplantation outcomes, and GPR56 may be a target for the treatment of type 2 diabetes.</description><identifier>ISSN: 1420-682X</identifier><identifier>EISSN: 1420-9071</identifier><identifier>DOI: 10.1007/s00018-018-2846-4</identifier><identifier>PMID: 29855662</identifier><language>eng</language><publisher>Cham: Springer International Publishing</publisher><subject>Animals ; Apoptosis ; Apoptosis - genetics ; Biochemistry ; Biomedical and Life Sciences ; Biomedicine ; Calcium (intracellular) ; Calcium - metabolism ; Calcium ions ; Capillaries ; Caspase ; Caspase-3 ; Cell Biology ; Cell proliferation ; Cell Proliferation - genetics ; Clonal deletion ; Collagen ; Collagen (type III) ; Collagen - genetics ; Diabetes mellitus ; Diabetes mellitus (non-insulin dependent) ; Diabetes Mellitus, Type 2 - genetics ; Diabetes Mellitus, Type 2 - metabolism ; Diabetes Mellitus, Type 2 - pathology ; Extracellular matrix ; Extracellular Matrix - genetics ; Extracellular Matrix - metabolism ; Fluorescence ; G protein-coupled receptors ; Gene Expression Regulation ; Glucose ; Glucose tolerance ; Homeostasis ; Humans ; Immunohistochemistry ; Immunological tolerance ; Innervation ; Insulin ; Insulin secretion ; Insulin-Secreting Cells - metabolism ; Insulin-Secreting Cells - pathology ; Islet cells ; Islets of Langerhans - metabolism ; Islets of Langerhans - pathology ; Life Sciences ; Mice ; Mice, Knockout ; Original ; Original Article ; Pancreas ; Pancreas - metabolism ; Pancreas - pathology ; Pancreatic islet transplantation ; Proteins ; Radioimmunoassay ; Receptors, G-Protein-Coupled - genetics ; Rodents ; Transplantation</subject><ispartof>Cellular and molecular life sciences : CMLS, 2018-11, Vol.75 (21), p.4007-4019</ispartof><rights>The Author(s) 2018</rights><rights>Cellular and Molecular Life Sciences is a copyright of Springer, (2018). All Rights Reserved. © 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3854-41257103b5d646df459e96aca290c1dde4dfd0af5b054ae39f368691b719236f3</citedby><cites>FETCH-LOGICAL-c3854-41257103b5d646df459e96aca290c1dde4dfd0af5b054ae39f368691b719236f3</cites><orcidid>0000-0002-4933-5958 ; 0000-0001-6830-2353</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6182347/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6182347/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,41488,42557,51319,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29855662$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Olaniru, Oladapo E.</creatorcontrib><creatorcontrib>Pingitore, Attilio</creatorcontrib><creatorcontrib>Giera, Stefanie</creatorcontrib><creatorcontrib>Piao, Xianhua</creatorcontrib><creatorcontrib>Castañera González, Ramón</creatorcontrib><creatorcontrib>Jones, Peter M.</creatorcontrib><creatorcontrib>Persaud, Shanta J.</creatorcontrib><title>The adhesion receptor GPR56 is activated by extracellular matrix collagen III to improve β-cell function</title><title>Cellular and molecular life sciences : CMLS</title><addtitle>Cell. Mol. Life Sci</addtitle><addtitle>Cell Mol Life Sci</addtitle><description>Aims G-protein coupled receptor 56 (GPR56) is the most abundant islet-expressed G-protein coupled receptor, suggesting a potential role in islet function. This study evaluated islet expression of GPR56 and its endogenous ligand collagen III, and their effects on β-cell function. Methods GPR56 and collagen III expression in mouse and human pancreas sections was determined by fluorescence immunohistochemistry. Effects of collagen III on β-cell proliferation, apoptosis, intracellular calcium ([Ca 2+ ] i ) and insulin secretion were determined by cellular BrdU incorporation, caspase 3/7 activities, microfluorimetry and radioimmunoassay, respectively. The role of GPR56 in islet vascularisation and innervation was evaluated by immunohistochemical staining for CD31 and TUJ1, respectively, in pancreases from wildtype (WT) and Gpr56 −/− mice, and the requirement of GPR56 for normal glucose homeostasis was determined by glucose tolerance tests in WT and Gpr56 −/− mice. Results Immunostaining of mouse and human pancreases revealed that GPR56 was expressed by islet β-cells while collagen III was confined to the peri-islet basement membrane and islet capillaries. Collagen III protected β-cells from cytokine-induced apoptosis, triggered increases in [Ca 2+ ] i and potentiated glucose-induced insulin secretion from WT islets but not from Gpr56 −/− islets. Deletion of GPR56 did not affect glucose-induced insulin secretion in vitro and it did not impair glucose tolerance in adult mice. GPR56 was not required for normal islet vascularisation or innervation. Conclusion We have demonstrated that collagen III improves islet function by increasing insulin secretion and protecting against apoptosis. Our data suggest that collagen III may be effective in optimising islet function to improve islet transplantation outcomes, and GPR56 may be a target for the treatment of type 2 diabetes.</description><subject>Animals</subject><subject>Apoptosis</subject><subject>Apoptosis - genetics</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Calcium (intracellular)</subject><subject>Calcium - metabolism</subject><subject>Calcium ions</subject><subject>Capillaries</subject><subject>Caspase</subject><subject>Caspase-3</subject><subject>Cell Biology</subject><subject>Cell proliferation</subject><subject>Cell Proliferation - genetics</subject><subject>Clonal deletion</subject><subject>Collagen</subject><subject>Collagen (type III)</subject><subject>Collagen - genetics</subject><subject>Diabetes mellitus</subject><subject>Diabetes mellitus (non-insulin dependent)</subject><subject>Diabetes Mellitus, Type 2 - genetics</subject><subject>Diabetes Mellitus, Type 2 - 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metabolism</subject><subject>Pancreas - pathology</subject><subject>Pancreatic islet transplantation</subject><subject>Proteins</subject><subject>Radioimmunoassay</subject><subject>Receptors, G-Protein-Coupled - genetics</subject><subject>Rodents</subject><subject>Transplantation</subject><issn>1420-682X</issn><issn>1420-9071</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp1kd9qFDEUxoMotlYfwBsJeOPN2CSTZCY3gpRaFwqVUsG7kEnO7KbMJGsys7Sv5YP4TGbYtf6BXhwSOL_z5Tv5EHpNyXtKSHOaCSG0rZZiLZcVf4KOKWekUqShTw932bJvR-hFzrcFFi2Tz9ERU60QUrJj5G82gI3bQPYx4AQWtlNM-OLLtZDYZ2zs5HdmAoe7ewx3UzIWhmEeTMKjmZK_wzYOg1lDwKvVCk8R-3Gb4g7wzx_VguJ-DkUjhpfoWW-GDK8O5wn6-un85uxzdXl1sTr7eFnZuhW84pSJhpK6E05y6XouFChprGGKWOoccNc7YnrREcEN1KqvZSsV7RqqWC37-gR92Otu524EZyEU04PeJj-adK-j8frfTvAbvY47LWnLat4UgXcHgRS_z5AnPfq8rGICxDlrRrgqv9dwUdC3_6G3cU6hrLdQjRLFGC0U3VM2xZwT9A9mKNFLkHofpF5qCVLzMvPm7y0eJn4nVwC2B3JphTWkP08_rvoL5i6p3Q</recordid><startdate>20181101</startdate><enddate>20181101</enddate><creator>Olaniru, Oladapo E.</creator><creator>Pingitore, Attilio</creator><creator>Giera, Stefanie</creator><creator>Piao, Xianhua</creator><creator>Castañera González, Ramón</creator><creator>Jones, Peter M.</creator><creator>Persaud, Shanta J.</creator><general>Springer International Publishing</general><general>Springer Nature B.V</general><scope>C6C</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>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SS</scope><scope>7T5</scope><scope>7T7</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U7</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7N</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PATMY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PYCSY</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-4933-5958</orcidid><orcidid>https://orcid.org/0000-0001-6830-2353</orcidid></search><sort><creationdate>20181101</creationdate><title>The adhesion receptor GPR56 is activated by extracellular matrix collagen III to improve β-cell function</title><author>Olaniru, Oladapo E. ; Pingitore, Attilio ; Giera, Stefanie ; Piao, Xianhua ; Castañera González, Ramón ; Jones, Peter M. ; Persaud, Shanta J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3854-41257103b5d646df459e96aca290c1dde4dfd0af5b054ae39f368691b719236f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Animals</topic><topic>Apoptosis</topic><topic>Apoptosis - genetics</topic><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Calcium (intracellular)</topic><topic>Calcium - metabolism</topic><topic>Calcium ions</topic><topic>Capillaries</topic><topic>Caspase</topic><topic>Caspase-3</topic><topic>Cell Biology</topic><topic>Cell proliferation</topic><topic>Cell Proliferation - genetics</topic><topic>Clonal deletion</topic><topic>Collagen</topic><topic>Collagen (type III)</topic><topic>Collagen - genetics</topic><topic>Diabetes mellitus</topic><topic>Diabetes mellitus (non-insulin dependent)</topic><topic>Diabetes Mellitus, Type 2 - genetics</topic><topic>Diabetes Mellitus, Type 2 - metabolism</topic><topic>Diabetes Mellitus, Type 2 - pathology</topic><topic>Extracellular matrix</topic><topic>Extracellular Matrix - genetics</topic><topic>Extracellular Matrix - metabolism</topic><topic>Fluorescence</topic><topic>G protein-coupled receptors</topic><topic>Gene Expression Regulation</topic><topic>Glucose</topic><topic>Glucose tolerance</topic><topic>Homeostasis</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Immunological tolerance</topic><topic>Innervation</topic><topic>Insulin</topic><topic>Insulin secretion</topic><topic>Insulin-Secreting Cells - metabolism</topic><topic>Insulin-Secreting Cells - pathology</topic><topic>Islet cells</topic><topic>Islets of Langerhans - metabolism</topic><topic>Islets of Langerhans - pathology</topic><topic>Life Sciences</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Original</topic><topic>Original Article</topic><topic>Pancreas</topic><topic>Pancreas - metabolism</topic><topic>Pancreas - pathology</topic><topic>Pancreatic islet transplantation</topic><topic>Proteins</topic><topic>Radioimmunoassay</topic><topic>Receptors, G-Protein-Coupled - genetics</topic><topic>Rodents</topic><topic>Transplantation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Olaniru, Oladapo E.</creatorcontrib><creatorcontrib>Pingitore, Attilio</creatorcontrib><creatorcontrib>Giera, Stefanie</creatorcontrib><creatorcontrib>Piao, Xianhua</creatorcontrib><creatorcontrib>Castañera González, Ramón</creatorcontrib><creatorcontrib>Jones, Peter M.</creatorcontrib><creatorcontrib>Persaud, Shanta J.</creatorcontrib><collection>SpringerOpen(OpenAccess)</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>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium &amp; Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>ProQuest - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cellular and molecular life sciences : CMLS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Olaniru, Oladapo E.</au><au>Pingitore, Attilio</au><au>Giera, Stefanie</au><au>Piao, Xianhua</au><au>Castañera González, Ramón</au><au>Jones, Peter M.</au><au>Persaud, Shanta J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The adhesion receptor GPR56 is activated by extracellular matrix collagen III to improve β-cell function</atitle><jtitle>Cellular and molecular life sciences : CMLS</jtitle><stitle>Cell. Mol. Life Sci</stitle><addtitle>Cell Mol Life Sci</addtitle><date>2018-11-01</date><risdate>2018</risdate><volume>75</volume><issue>21</issue><spage>4007</spage><epage>4019</epage><pages>4007-4019</pages><issn>1420-682X</issn><eissn>1420-9071</eissn><abstract>Aims G-protein coupled receptor 56 (GPR56) is the most abundant islet-expressed G-protein coupled receptor, suggesting a potential role in islet function. This study evaluated islet expression of GPR56 and its endogenous ligand collagen III, and their effects on β-cell function. Methods GPR56 and collagen III expression in mouse and human pancreas sections was determined by fluorescence immunohistochemistry. Effects of collagen III on β-cell proliferation, apoptosis, intracellular calcium ([Ca 2+ ] i ) and insulin secretion were determined by cellular BrdU incorporation, caspase 3/7 activities, microfluorimetry and radioimmunoassay, respectively. The role of GPR56 in islet vascularisation and innervation was evaluated by immunohistochemical staining for CD31 and TUJ1, respectively, in pancreases from wildtype (WT) and Gpr56 −/− mice, and the requirement of GPR56 for normal glucose homeostasis was determined by glucose tolerance tests in WT and Gpr56 −/− mice. Results Immunostaining of mouse and human pancreases revealed that GPR56 was expressed by islet β-cells while collagen III was confined to the peri-islet basement membrane and islet capillaries. Collagen III protected β-cells from cytokine-induced apoptosis, triggered increases in [Ca 2+ ] i and potentiated glucose-induced insulin secretion from WT islets but not from Gpr56 −/− islets. Deletion of GPR56 did not affect glucose-induced insulin secretion in vitro and it did not impair glucose tolerance in adult mice. GPR56 was not required for normal islet vascularisation or innervation. Conclusion We have demonstrated that collagen III improves islet function by increasing insulin secretion and protecting against apoptosis. Our data suggest that collagen III may be effective in optimising islet function to improve islet transplantation outcomes, and GPR56 may be a target for the treatment of type 2 diabetes.</abstract><cop>Cham</cop><pub>Springer International Publishing</pub><pmid>29855662</pmid><doi>10.1007/s00018-018-2846-4</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0002-4933-5958</orcidid><orcidid>https://orcid.org/0000-0001-6830-2353</orcidid><oa>free_for_read</oa></addata></record>
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subjects Animals
Apoptosis
Apoptosis - genetics
Biochemistry
Biomedical and Life Sciences
Biomedicine
Calcium (intracellular)
Calcium - metabolism
Calcium ions
Capillaries
Caspase
Caspase-3
Cell Biology
Cell proliferation
Cell Proliferation - genetics
Clonal deletion
Collagen
Collagen (type III)
Collagen - genetics
Diabetes mellitus
Diabetes mellitus (non-insulin dependent)
Diabetes Mellitus, Type 2 - genetics
Diabetes Mellitus, Type 2 - metabolism
Diabetes Mellitus, Type 2 - pathology
Extracellular matrix
Extracellular Matrix - genetics
Extracellular Matrix - metabolism
Fluorescence
G protein-coupled receptors
Gene Expression Regulation
Glucose
Glucose tolerance
Homeostasis
Humans
Immunohistochemistry
Immunological tolerance
Innervation
Insulin
Insulin secretion
Insulin-Secreting Cells - metabolism
Insulin-Secreting Cells - pathology
Islet cells
Islets of Langerhans - metabolism
Islets of Langerhans - pathology
Life Sciences
Mice
Mice, Knockout
Original
Original Article
Pancreas
Pancreas - metabolism
Pancreas - pathology
Pancreatic islet transplantation
Proteins
Radioimmunoassay
Receptors, G-Protein-Coupled - genetics
Rodents
Transplantation
title The adhesion receptor GPR56 is activated by extracellular matrix collagen III to improve β-cell function
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