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University of Pennsylvania | 1. Dept of Biochemistry and Biophysics. 2. School of Chemistry - Academia.edu

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Dept of Biochemistry and Biophysics. 2. School of Chemistry</h1></div><div class="u-floatRight u-mt1x"></div></div></div></div></div><div class="TabbedNavigation"><div class="container"><div class="row"><div class="col-xs-12 clearfix"><ul class="nav u-m0x u-p0x list-inline"><li class="u-floatLeft u-pr5x u-mr5x u-borderColorGrayLight u-borderRight1"><a href="https://upenn.academia.edu/"><span><i class="fa fa-arrow-left"></i>&nbsp;&nbsp;All Departments</span></a></li><li class="u-floatLeft active"><a href="https://upenn.academia.edu/Departments/1_Dept_of_Biochemistry_and_Biophysics_2_School_of_Chemistry/Documents">328 Papers</a></li><li class="u-floatLeft"><a href="https://upenn.academia.edu/Departments/1_Dept_of_Biochemistry_and_Biophysics_2_School_of_Chemistry">40 Researchers</a></li></ul></div></div></div></div><div class="container"><div class="row"><div class="col-xs-12"><div class="u-displayFlex"><div class="u-flexGrow1"><div class="u-ph0x"><div class="works"><div class="u-borderBottom1 u-borderColorGrayLighter"><div 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Function</a></div></div><div class="u-pb4x u-mt3x"><div class="summary u-fs14 u-fw300 u-lineHeight1_5 u-tcGrayDarkest"><div class="summarized">Uncoupling protein (UCP) 2 is a widely expressed mitochondrial protein whose precise function is still unclear but has been linked to mitochondria-derived reactive oxygen species production. Thus, the chronic absence of UCP2 has the... <a class="more_link u-tcGrayDark u-linkUnstyled" data-container=".work_53418005" data-show=".complete" data-hide=".summarized" data-more-link-behavior="true" href="#">more</a></div><div class="complete hidden">Uncoupling protein (UCP) 2 is a widely expressed mitochondrial protein whose precise function is still unclear but has been linked to mitochondria-derived reactive oxygen species production. Thus, the chronic absence of UCP2 has the potential to promote persistent reactive oxygen species accumulation and an oxidative stress response. Here, we show that Ucp2−/− mice on three highly congenic (N &amp;gt;10) strain backgrounds (C57BL/6J, A/J, 129/SvImJ), including two independently generated sources of Ucp2-null animals, all exhibit increased oxidative stress. Ucp2-null animals exhibit a decreased ratio of reduced glutathione to its oxidized form in blood and tissues that normally express UCP2, including pancreatic islets. Islets from Ucp2−/− mice exhibit elevated levels of numerous antioxidant enzymes, increased nitrotyrosine and F4/80 staining, but no change in insulin content. Contrary to results in Ucp2−/− mice of mixed 129/B6 strain background, glucose-stimulated insulin secretion in U...</div></div></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/53418005" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="15c7e7f5a5fd2e3b3b36d2fd00b48c71" rel="nofollow" data-download="{&quot;attachment_id&quot;:70271940,&quot;asset_id&quot;:53418005,&quot;asset_type&quot;:&quot;Work&quot;,&quot;always_allow_download&quot;:false,&quot;track&quot;:null,&quot;button_location&quot;:&quot;work_strip&quot;,&quot;source&quot;:null,&quot;hide_modal&quot;:null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button doc_download" href="https://www.academia.edu/attachments/70271940/download_file?st=MTczMjgzMzM0Niw4LjIyMi4yMDguMTQ2&s=work_strip"><i class="fa fa-arrow-circle-o-down fa-lg"></i><span class="u-textUppercase u-ml1x" data-content="button_text">Download</span></a></div></li><li class="InlineList-item"><ul class="InlineList InlineList--bordered u-ph0x"><li class="InlineList-item InlineList-item--bordered"><span class="InlineList-item-text">by&nbsp;<span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a class="u-tcGrayDark u-fw700" data-has-card-for-user="16608156" href="https://upenn.academia.edu/BarbaraCorkey">Barbara Corkey</a><script data-card-contents-for-user="16608156" type="text/json">{"id":16608156,"first_name":"Barbara","last_name":"Corkey","domain_name":"upenn","page_name":"BarbaraCorkey","display_name":"Barbara Corkey","profile_url":"https://upenn.academia.edu/BarbaraCorkey","photo":"/images/s65_no_pic.png"}</script></span></span></li><li class="js-paper-rank-work_53418005 InlineList-item InlineList-item--bordered hidden"><span class="js-paper-rank-view hidden u-tcGrayDark" data-paper-rank-work-id="53418005"><i class="u-m1x fa fa-bar-chart"></i><strong class="js-paper-rank"></strong></span><script>$(function() { new Works.PaperRankView({ workId: 53418005, container: ".js-paper-rank-work_53418005", }); 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Thus, the chronic absence of UCP2 has the potential to promote persistent reactive oxygen species accumulation and an oxidative stress response. Here, we show that Ucp2−/− mice on three highly congenic (N \u0026gt;10) strain backgrounds (C57BL/6J, A/J, 129/SvImJ), including two independently generated sources of Ucp2-null animals, all exhibit increased oxidative stress. Ucp2-null animals exhibit a decreased ratio of reduced glutathione to its oxidized form in blood and tissues that normally express UCP2, including pancreatic islets. Islets from Ucp2−/− mice exhibit elevated levels of numerous antioxidant enzymes, increased nitrotyrosine and F4/80 staining, but no change in insulin content. Contrary to results in Ucp2−/− mice of mixed 129/B6 strain background, glucose-stimulated insulin secretion in 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href="https://www.academia.edu/53418232/Temporal_patterns_of_changes_in_ATP_ADP_ratio_glucose_6_phosphate_and_cytoplasmic_free_Ca2_in_glucose_stimulated_pancreatic_beta_cells">Temporal patterns of changes in ATP/ADP ratio, glucose 6-phosphate and cytoplasmic free Ca2+ in glucose-stimulated pancreatic beta-cells</a></div></div><div class="u-pb4x u-mt3x"><div class="summary u-fs14 u-fw300 u-lineHeight1_5 u-tcGrayDarkest"><div class="summarized">Closure of ATP-sensitive K+ (K(ATP)) channels is part of the stimulus-secretion coupling mechanism in the pancreatic beta-cell, leading to membrane depolarization and influx of Ca2+ through voltage-sensitive L-type Ca2+ channels. The... <a class="more_link u-tcGrayDark u-linkUnstyled" data-container=".work_53418232" data-show=".complete" data-hide=".summarized" data-more-link-behavior="true" href="#">more</a></div><div class="complete hidden">Closure of ATP-sensitive K+ (K(ATP)) channels is part of the stimulus-secretion coupling mechanism in the pancreatic beta-cell, leading to membrane depolarization and influx of Ca2+ through voltage-sensitive L-type Ca2+ channels. The elevated ATP/ADP ratio seen in the presence of high levels of glucose has been postulated to mediate the glucose-induced closure of the K(ATP) channels and rise in cytoplasmic free Ca2+ concentration ([Ca2+]i), or alternatively to be a consequence of activation of mitochondrial dehydrogenases by the increase in [Ca2+]i. To distinguish between these two possibilities, the time course of the change in the ATP/ADP ratio was determined in comparison with that of [Ca2+]i. We here show that a severalfold rise in the ATP/ADP ratio occurs rapidly on stimulation of suspensions of mouse pancreatic beta-cells with glucose. The change in the ATP/ADP ratio is an early event that begins within 20-40 s and precedes the rise in [Ca2+]i. The temporal relationship indica...</div></div></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/53418232" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="d8826c2af3307c34ea5e25bca06ef680" rel="nofollow" data-download="{&quot;attachment_id&quot;:70272064,&quot;asset_id&quot;:53418232,&quot;asset_type&quot;:&quot;Work&quot;,&quot;always_allow_download&quot;:false,&quot;track&quot;:null,&quot;button_location&quot;:&quot;work_strip&quot;,&quot;source&quot;:null,&quot;hide_modal&quot;:null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button doc_download" href="https://www.academia.edu/attachments/70272064/download_file?st=MTczMjgzMzM0Niw4LjIyMi4yMDguMTQ2&s=work_strip"><i class="fa fa-arrow-circle-o-down fa-lg"></i><span class="u-textUppercase u-ml1x" data-content="button_text">Download</span></a></div></li><li class="InlineList-item"><ul class="InlineList InlineList--bordered u-ph0x"><li class="InlineList-item InlineList-item--bordered"><span class="InlineList-item-text">by&nbsp;<span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a class="u-tcGrayDark u-fw700" data-has-card-for-user="16608156" href="https://upenn.academia.edu/BarbaraCorkey">Barbara Corkey</a><script data-card-contents-for-user="16608156" type="text/json">{"id":16608156,"first_name":"Barbara","last_name":"Corkey","domain_name":"upenn","page_name":"BarbaraCorkey","display_name":"Barbara Corkey","profile_url":"https://upenn.academia.edu/BarbaraCorkey","photo":"/images/s65_no_pic.png"}</script></span></span></li><li class="js-paper-rank-work_53418232 InlineList-item InlineList-item--bordered hidden"><span class="js-paper-rank-view hidden u-tcGrayDark" data-paper-rank-work-id="53418232"><i class="u-m1x fa fa-bar-chart"></i><strong class="js-paper-rank"></strong></span><script>$(function() { new Works.PaperRankView({ workId: 53418232, container: ".js-paper-rank-work_53418232", }); 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The elevated ATP/ADP ratio seen in the presence of high levels of glucose has been postulated to mediate the glucose-induced closure of the K(ATP) channels and rise in cytoplasmic free Ca2+ concentration ([Ca2+]i), or alternatively to be a consequence of activation of mitochondrial dehydrogenases by the increase in [Ca2+]i. To distinguish between these two possibilities, the time course of the change in the ATP/ADP ratio was determined in comparison with that of [Ca2+]i. We here show that a severalfold rise in the ATP/ADP ratio occurs rapidly on stimulation of suspensions of mouse pancreatic beta-cells with glucose. The change in the ATP/ADP ratio is an early event that begins within 20-40 s and precedes the rise in [Ca2+]i. 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