Increased Activity of L-Type Ca$^{2+}$ Channels Exposed to Serum from Patients with Type I Diabetes
Type I diabetes [insulin-dependent diabetes mellitus (IDDM)] is an autoimmune disease associated with the destruction of pancreatic β cells. Serum from patients with IDDM increased L-type calcium channel activity of insulin-producing cells and of GH$_3$ cells derived from a pituitary tumor. The subs...
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| Veröffentlicht in: | Science (American Association for the Advancement of Science) 1993-07, Vol.261 (5117), p.86-90 |
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| container_title | Science (American Association for the Advancement of Science) |
| container_volume | 261 |
| creator | Juntti-Berggren, Lisa Larsson, Olof Rorsman, Patrik Ämmälä, Carina Bokvist, Krister Wåhlander, Karin Nicotera, Pierluigi Dypbukt, Jeanette Orrenius, Sten Hallberg, Anders Berggren, Per-Olof |
| description | Type I diabetes [insulin-dependent diabetes mellitus (IDDM)] is an autoimmune disease associated with the destruction of pancreatic β cells. Serum from patients with IDDM increased L-type calcium channel activity of insulin-producing cells and of GH$_3$ cells derived from a pituitary tumor. The subsequent increase in the concentration of free cytoplasmic Ca$^{2+}$ ([Ca$^{2+}$]$_i$) was associated with DNA fragmentation typical of programmed cell death or apoptosis. These effects of the serum were prevented by adding a blocker of voltage-activated L-type Ca$^{2+}$ channels. When the serum was depleted of immunoglobulin M (IgM), it no longer affected [Ca$^{2+}$]$_i$. An IgM-mediated increase in Ca$^{2+}$ influx may thus be part of the autoimmune reaction associated with IDDM and contribute to the destruction of β cells in vivo. |
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Serum from patients with IDDM increased L-type calcium channel activity of insulin-producing cells and of GH$_3$ cells derived from a pituitary tumor. The subsequent increase in the concentration of free cytoplasmic Ca$^{2+}$ ([Ca$^{2+}$]$_i$) was associated with DNA fragmentation typical of programmed cell death or apoptosis. These effects of the serum were prevented by adding a blocker of voltage-activated L-type Ca$^{2+}$ channels. When the serum was depleted of immunoglobulin M (IgM), it no longer affected [Ca$^{2+}$]$_i$. An IgM-mediated increase in Ca$^{2+}$ influx may thus be part of the autoimmune reaction associated with IDDM and contribute to the destruction of β cells in vivo.</description><identifier>ISSN: 0036-8075</identifier><identifier>EISSN: 1095-9203</identifier><language>eng</language><publisher>American Society for the Advancement of Science</publisher><subject>Apoptosis ; Beta cells ; Depolarization ; Diabetes ; DNA fragmentation ; Electric potential ; Islet cells ; Pancreatic cells ; T tests ; Type 1 diabetes mellitus</subject><ispartof>Science (American Association for the Advancement of Science), 1993-07, Vol.261 (5117), p.86-90</ispartof><rights>Copyright 1993 American Association for the Advancement of Science</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/2881471$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/2881471$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>314,776,780,799,57992,58225</link.rule.ids></links><search><creatorcontrib>Juntti-Berggren, Lisa</creatorcontrib><creatorcontrib>Larsson, Olof</creatorcontrib><creatorcontrib>Rorsman, Patrik</creatorcontrib><creatorcontrib>Ämmälä, Carina</creatorcontrib><creatorcontrib>Bokvist, Krister</creatorcontrib><creatorcontrib>Wåhlander, Karin</creatorcontrib><creatorcontrib>Nicotera, Pierluigi</creatorcontrib><creatorcontrib>Dypbukt, Jeanette</creatorcontrib><creatorcontrib>Orrenius, Sten</creatorcontrib><creatorcontrib>Hallberg, Anders</creatorcontrib><creatorcontrib>Berggren, Per-Olof</creatorcontrib><title>Increased Activity of L-Type Ca$^{2+}$ Channels Exposed to Serum from Patients with Type I Diabetes</title><title>Science (American Association for the Advancement of Science)</title><description>Type I diabetes [insulin-dependent diabetes mellitus (IDDM)] is an autoimmune disease associated with the destruction of pancreatic β cells. Serum from patients with IDDM increased L-type calcium channel activity of insulin-producing cells and of GH$_3$ cells derived from a pituitary tumor. The subsequent increase in the concentration of free cytoplasmic Ca$^{2+}$ ([Ca$^{2+}$]$_i$) was associated with DNA fragmentation typical of programmed cell death or apoptosis. These effects of the serum were prevented by adding a blocker of voltage-activated L-type Ca$^{2+}$ channels. When the serum was depleted of immunoglobulin M (IgM), it no longer affected [Ca$^{2+}$]$_i$. An IgM-mediated increase in Ca$^{2+}$ influx may thus be part of the autoimmune reaction associated with IDDM and contribute to the destruction of β cells in vivo.</description><subject>Apoptosis</subject><subject>Beta cells</subject><subject>Depolarization</subject><subject>Diabetes</subject><subject>DNA fragmentation</subject><subject>Electric potential</subject><subject>Islet cells</subject><subject>Pancreatic cells</subject><subject>T tests</subject><subject>Type 1 diabetes mellitus</subject><issn>0036-8075</issn><issn>1095-9203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1993</creationdate><recordtype>article</recordtype><sourceid/><recordid>eNotjMtKxDAYRoMoWEffwEUWs5NArtNkOdRRCwUFu3ZIM3-YlOmFJl6K-O6Ol9VZfOc7Jyhj1ChiOBWnKKNUrIimuTpHFzG2lB43IzLkyt5NYCPs8Nql8BbSjAePK1LPI-DCLl8--c3XEhd72_dwiHjzMQ4_dhrwM0yvHfbT0OEnmwL0KeL3kPb491vi22AbSBAv0Zm3hwhX_1yg-m5TFw-kerwvi3VFWm0S8d4a5sHl0rqcCSckMy73hgtGJZfSKNpo0N5z5W3OGuMdUyCN3AnBlV2JBbr-y7YxDdN2nEJnp3nLtWbyGPwGOT9Ofw</recordid><startdate>19930702</startdate><enddate>19930702</enddate><creator>Juntti-Berggren, Lisa</creator><creator>Larsson, Olof</creator><creator>Rorsman, Patrik</creator><creator>Ämmälä, Carina</creator><creator>Bokvist, Krister</creator><creator>Wåhlander, Karin</creator><creator>Nicotera, Pierluigi</creator><creator>Dypbukt, Jeanette</creator><creator>Orrenius, Sten</creator><creator>Hallberg, Anders</creator><creator>Berggren, Per-Olof</creator><general>American Society for the Advancement of Science</general><scope/></search><sort><creationdate>19930702</creationdate><title>Increased Activity of L-Type Ca$^{2+}$ Channels Exposed to Serum from Patients with Type I Diabetes</title><author>Juntti-Berggren, Lisa ; Larsson, Olof ; Rorsman, Patrik ; Ämmälä, Carina ; Bokvist, Krister ; Wåhlander, Karin ; Nicotera, Pierluigi ; Dypbukt, Jeanette ; Orrenius, Sten ; Hallberg, Anders ; Berggren, Per-Olof</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-j89t-ffa91fec74ac713c3419c7f923104244950b8e8ff25fa71b9fc15e494d3325a63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1993</creationdate><topic>Apoptosis</topic><topic>Beta cells</topic><topic>Depolarization</topic><topic>Diabetes</topic><topic>DNA fragmentation</topic><topic>Electric potential</topic><topic>Islet cells</topic><topic>Pancreatic cells</topic><topic>T tests</topic><topic>Type 1 diabetes mellitus</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Juntti-Berggren, Lisa</creatorcontrib><creatorcontrib>Larsson, Olof</creatorcontrib><creatorcontrib>Rorsman, Patrik</creatorcontrib><creatorcontrib>Ämmälä, Carina</creatorcontrib><creatorcontrib>Bokvist, Krister</creatorcontrib><creatorcontrib>Wåhlander, Karin</creatorcontrib><creatorcontrib>Nicotera, Pierluigi</creatorcontrib><creatorcontrib>Dypbukt, Jeanette</creatorcontrib><creatorcontrib>Orrenius, Sten</creatorcontrib><creatorcontrib>Hallberg, Anders</creatorcontrib><creatorcontrib>Berggren, Per-Olof</creatorcontrib><jtitle>Science (American Association for the Advancement of Science)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Juntti-Berggren, Lisa</au><au>Larsson, Olof</au><au>Rorsman, Patrik</au><au>Ämmälä, Carina</au><au>Bokvist, Krister</au><au>Wåhlander, Karin</au><au>Nicotera, Pierluigi</au><au>Dypbukt, Jeanette</au><au>Orrenius, Sten</au><au>Hallberg, Anders</au><au>Berggren, Per-Olof</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Increased Activity of L-Type Ca$^{2+}$ Channels Exposed to Serum from Patients with Type I Diabetes</atitle><jtitle>Science (American Association for the Advancement of Science)</jtitle><date>1993-07-02</date><risdate>1993</risdate><volume>261</volume><issue>5117</issue><spage>86</spage><epage>90</epage><pages>86-90</pages><issn>0036-8075</issn><eissn>1095-9203</eissn><abstract>Type I diabetes [insulin-dependent diabetes mellitus (IDDM)] is an autoimmune disease associated with the destruction of pancreatic β cells. Serum from patients with IDDM increased L-type calcium channel activity of insulin-producing cells and of GH$_3$ cells derived from a pituitary tumor. The subsequent increase in the concentration of free cytoplasmic Ca$^{2+}$ ([Ca$^{2+}$]$_i$) was associated with DNA fragmentation typical of programmed cell death or apoptosis. These effects of the serum were prevented by adding a blocker of voltage-activated L-type Ca$^{2+}$ channels. When the serum was depleted of immunoglobulin M (IgM), it no longer affected [Ca$^{2+}$]$_i$. An IgM-mediated increase in Ca$^{2+}$ influx may thus be part of the autoimmune reaction associated with IDDM and contribute to the destruction of β cells in vivo.</abstract><pub>American Society for the Advancement of Science</pub><tpages>5</tpages></addata></record> |
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| identifier | ISSN: 0036-8075 |
| ispartof | Science (American Association for the Advancement of Science), 1993-07, Vol.261 (5117), p.86-90 |
| issn | 0036-8075 1095-9203 |
| language | eng |
| recordid | cdi_jstor_primary_2881471 |
| source | American Association for the Advancement of Science; Jstor Complete Legacy |
| subjects | Apoptosis Beta cells Depolarization Diabetes DNA fragmentation Electric potential Islet cells Pancreatic cells T tests Type 1 diabetes mellitus |
| title | Increased Activity of L-Type Ca$^{2+}$ Channels Exposed to Serum from Patients with Type I Diabetes |
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