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(PDF) Pathways through which glucose induces a rise in [Ca2+]i of polymorphonuclear leukocytes of rats
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Basal levels of [Ca2}i arc elevated in diabetes mellitus. Such an abnormality is most likely due to both increased calcium influx into cells and decreased efflux of this ion out of the cells. 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if (!viewCountBody) { throw new Error('Failed to find work views element'); } viewCountBody.textContent = `${commaizedViewCount} views`; } catch (error) { // Remove the whole views element if there was some issue parsing. document.getElementById('work-metadata-view-count')?.parentNode?.remove(); throw new Error(`Failed to parse view count: ${viewCount}`, error); } }; // If the DOM is still loading, wait for it to be ready before updating the view count. if (document.readyState === "loading") { document.addEventListener('DOMContentLoaded', () => { updateViewCount(viewCount); }); // Otherwise, just update it immediately. } else { updateViewCount(viewCount); } })();</script></div><p class="ds-work-card--work-abstract ds-work-card--detail ds2-5-body-md">Pathways through which glucose induces a rise in [Ca2]i of polymorphonuclear leukocytes of rats. Basal levels of [Ca2}i arc elevated in diabetes mellitus. Such an abnormality is most likely due to both increased calcium influx into cells and decreased efflux of this ion out of the cells. The present study examined the cellular pathways that are responsible for</p><div class="ds-work-card--button-container"><div class="primary-buttons "><button class="ds2-5-button js-swp-download-button" data-signup-modal="{"location":"continue-reading-button--work-card","attachmentId":42688934,"attachmentType":"pdf","workUrl":"https://www.academia.edu/21975515/Pathways_through_which_glucose_induces_a_rise_in_Ca2_i_of_polymorphonuclear_leukocytes_of_rats"}"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">description</span>See full PDF</button><button class="ds2-5-button ds2-5-button--secondary js-swp-download-button" data-signup-modal="{"location":"download-pdf-button--work-card","attachmentId":42688934,"attachmentType":"pdf","workUrl":"https://www.academia.edu/21975515/Pathways_through_which_glucose_induces_a_rise_in_Ca2_i_of_polymorphonuclear_leukocytes_of_rats"}"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">download</span>Download PDF</button></div></div><div class="ds-signup-banner-trigger-container"><div class="ds-signup-banner-trigger ds-signup-banner-trigger-control"></div></div><div class="ds-signup-banner ds-signup-banner-control"><div id="ds-signup-banner-close-button"><button class="ds2-5-button ds2-5-button--secondary ds2-5-button--inverse"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">close</span></button></div><div class="ds-signup-banner-ctas" data-impression-entity-id="21975515" data-impression-entity-type="2" data-impression-source="signup-banner"><img src="//a.academia-assets.com/images/academia-logo-capital-white.svg" /><h4 class="ds2-5-heading-serif-sm">Sign up for access to the world's latest research</h4><button class="ds2-5-button ds2-5-button--inverse ds2-5-button--full-width js-swp-download-button" data-signup-modal="{"location":"signup-banner"}">Sign up for free<span class="material-symbols-outlined" style="font-size: 20px" translate="no">arrow_forward</span></button></div><div class="ds-signup-banner-divider"></div><div class="ds-signup-banner-reasons"><div class="ds-signup-banner-reasons-item"><span class="material-symbols-outlined" style="font-size: 24px" translate="no">check</span><span>Get notified about relevant papers</span></div><div class="ds-signup-banner-reasons-item"><span class="material-symbols-outlined" style="font-size: 24px" translate="no">check</span><span>Save papers to use in your research</span></div><div class="ds-signup-banner-reasons-item"><span class="material-symbols-outlined" style="font-size: 24px" translate="no">check</span><span>Join the discussion with peers</span></div><div class="ds-signup-banner-reasons-item"><span class="material-symbols-outlined" style="font-size: 24px" translate="no">check</span><span>Track your impact</span></div></div></div><script>(() => { // Set up signup banner show/hide behavior: // 1. 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Basal levels of [Ca2}i arc elevated in diabetes mellitus. Such an abnormality is most likely due to both increased calcium influx into cells and decreased efflux of this ion out of the cells. The present study examined the cellular pathways that are responsible for</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"The pathways through which glucose induces a rise in [Ca] i of PMNLs of rats","attachmentId":78009825,"attachmentType":"pdf","work_url":"https://www.academia.edu/67040654/The_pathways_through_which_glucose_induces_a_rise_in_Ca_i_of_PMNLs_of_rats","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/67040654/The_pathways_through_which_glucose_induces_a_rise_in_Ca_i_of_PMNLs_of_rats"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="1" data-entity-id="16685419" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/16685419/Delayed_Ca2_Response_to_Glucose_in_Diabetic_GK_Rat">Delayed Ca2+Response to Glucose in Diabetic GK Rat</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="35858326" href="https://independent.academia.edu/SZaitsev">Sergei Zaitsev</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Biochemical and Biophysical Research Communications, 1997</p><p class="ds-related-work--abstract ds2-5-body-sm">The spontaneously diabetic non-obese GK (Goto-Kakizaki) rat exhibits high basal plasma glucose and insulin levels and poor glucose-induced insulin secretion, which makes it a suitable model for non-insulin dependent diabetes mellitus, NIDDM. The aim of this study was to investigate the handling of cytosolic free Ca2+ concentration ([Ca2+]i), the key regulator of insulin secretion, in GK rat single pancreatic islets. For this purpose the influence of high glucose (16.7 mM) and arginine (20 mM) on [Ca2+]i was studied in GK and Wistar rat islets, which served as controls. The data obtained suggest that glucose which through its metabolism generates ATP needed for closure of the KATP channels and membrane depolarization, induces a delayed [Ca2+]i response in the GK rat pancreatic islet. This delay in [Ca2+]i response is likely to result from a defective metabolism of glucose in the diabetic islet.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Delayed Ca2+Response to Glucose in Diabetic GK Rat","attachmentId":42416201,"attachmentType":"pdf","work_url":"https://www.academia.edu/16685419/Delayed_Ca2_Response_to_Glucose_in_Diabetic_GK_Rat","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/16685419/Delayed_Ca2_Response_to_Glucose_in_Diabetic_GK_Rat"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="2" data-entity-id="33099057" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/33099057/Dual_effect_of_glucose_on_cytoplasmic_free_Ca2_concentration_and_insulin_release_reflects_the_%CE%B2_cell_being_deprived_of_fuel">Dual effect of glucose on cytoplasmic free Ca2+ concentration and insulin release reflects the β-cell being deprived of fuel</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="64502272" href="https://independent.academia.edu/PerArkhammar">Per Arkhammar</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Biochemical and Biophysical Research Communications, 1988</p><p class="ds-related-work--abstract ds2-5-body-sm">Influence of basal glucose concentration on the response evoked by subsequent stimulation with the sugar, was evaluated by investigating changes in free cytoplasmic Ca 2+ concentration, [Ca2+]i, and insulin release, using [3-cells isolated from obese hyperglycemic mice. When increasing the glucose concentration from 0 to either 11 or 20 raM, there was a transient decrease in both [Ca2+]i and insulin release. The decrease was followed by a pronounced increase in both of the parameters. When increasing the basal glucose concentration, the initial decrease gradually disappeared, being abolished already at 5 mM of the sugar and the subsequent increase appeared more rapidly. It is suggested that the observed decrease in [Ca2+]i and thereby insulin release reflects a phenomenon associated with fuel deprived B-cells. © zge8 A~,d~ Press, znc.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Dual effect of glucose on cytoplasmic free Ca2+ concentration and insulin release reflects the β-cell being deprived of fuel","attachmentId":53196734,"attachmentType":"pdf","work_url":"https://www.academia.edu/33099057/Dual_effect_of_glucose_on_cytoplasmic_free_Ca2_concentration_and_insulin_release_reflects_the_%CE%B2_cell_being_deprived_of_fuel","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/33099057/Dual_effect_of_glucose_on_cytoplasmic_free_Ca2_concentration_and_insulin_release_reflects_the_%CE%B2_cell_being_deprived_of_fuel"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="3" data-entity-id="30157226" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/30157226/Defective_glucose_dependent_cytosolic_Ca2_handling_in_islets_of_GK_and_nSTZ_rat_models_of_type_2_diabetes">Defective glucose-dependent cytosolic Ca2+ handling in islets of GK and nSTZ rat models of type 2 diabetes</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="57399477" href="https://independent.academia.edu/BernardPortha">Bernard Portha</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Journal of Endocrinology, 2001</p><p class="ds-related-work--abstract ds2-5-body-sm">We examined to what extent the abnormal glucosedependent insulin secretion observed in NIDDM (noninsulin-dependent diabetes mellitus) is related to alterations in the handling of cytosolic Ca 2+ of islets of Langerhans. Using two recognized rat models of NIDDM, the GK (Goto-Kakizaki) spontaneous model and the nSTZ (neonatal streptozotocin) induced model, we could detect several common alterations in the glucose-induced [Ca 2+ ] i cytosolic responses. First, the initial reduction of [Ca 2+ ] i following high glucose (16·7 mM) observed routinely in islets obtained from non-diabetic Wistar rats could not be detected in GK and nSTZ islets. Second, a delayed response for glucose to induce a subsequent 3% increase of [Ca 2+ ] i over basal level was observed in both GK (321 40 s, n=11) and nSTZ (326 38 s, n=13) islets as compared with Wistar islets (198 20 s, n=11), values representing means ... Third, the rate of increase in [Ca 2+ ] i in response to a high glucose challenge was 25% and 40% lower in GK and nSTZ respectively, as compared with Wistar islets. Fourth, the maximal [Ca 2+ ] i level reached after 10 min of perifusion with 16·7 mM glucose was lower with GK and nSTZ islets and represented respectively 60% and 90% of that of Wistar islets. Further, thapsigargin, a blocker of Ca 2+ -ATPases (SERCA), abolished the initial reduction in [Ca 2+ ] i observed in response to high glucose and induced fast [Ca 2+ ] i oscillations with high amplitude in Wistar islets. The latter effect was not seen in GK and nSTZ islets. In these two NIDDM models, several common alterations in glucoseinduced Ca 2+ handling were revealed which may contribute to their poor glucose-induced insulin secretion.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Defective glucose-dependent cytosolic Ca2+ handling in islets of GK and nSTZ rat models of type 2 diabetes","attachmentId":50614182,"attachmentType":"pdf","work_url":"https://www.academia.edu/30157226/Defective_glucose_dependent_cytosolic_Ca2_handling_in_islets_of_GK_and_nSTZ_rat_models_of_type_2_diabetes","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/30157226/Defective_glucose_dependent_cytosolic_Ca2_handling_in_islets_of_GK_and_nSTZ_rat_models_of_type_2_diabetes"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="4" data-entity-id="47958580" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/47958580/Evidence_for_Mechanistic_Alterations_of_Ca2_Homeostasis_in_Type_2_Diabetes_Mellitus">Evidence for Mechanistic Alterations of Ca2+ Homeostasis in Type 2 Diabetes Mellitus</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="20774826" href="https://mdrf.academia.edu/MuthuswamyBalasubramanyam">Muthuswamy Balasubramanyam</a></div><p class="ds-related-work--metadata ds2-5-body-xs">International Journal of Experimental Diabetes Research, 2000</p><p class="ds-related-work--abstract ds2-5-body-sm">Altered cytosolicCa2+is implicated in the aetiology of many diseases including diabetes but there are few studies on the mechanism(s) of the alteredCa2+regulation. Using human lymphocytes, we studied cytosolic calcium (Cai) and variousCa2+transport mechanisms in subjects with Type 2 diabetes mellitus and control subjects.Ca2+-specific fluorescent probes (Fura-2 and Fluo-3) were used to monitor theCa2+signals. Thapsigargin, a potent and specific inhibitor of the sarco(endo)plasmic reticulumCa2+-ATPase (SERCA), was used to studyCa2+- store dependentCa2+fluxes. Significant (P&lt; 0.05) elevation of basalCailevels was observed in lymphocytes from diabetic subjects.Cailevels were positively correlated with fasting, plasma glucose and HbAlc. There was also a significant (P&lt; 0.05) reduction in plasma membrane calcium (PMCA) ATPase activity in diabetic subjects compared to controls. Cells from Type 2 diabetics exhibited an increasedCa2+influx (as measured both by Fluo-3 fliorescence andC...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Evidence for Mechanistic Alterations of Ca2+ Homeostasis in Type 2 Diabetes Mellitus","attachmentId":66820131,"attachmentType":"pdf","work_url":"https://www.academia.edu/47958580/Evidence_for_Mechanistic_Alterations_of_Ca2_Homeostasis_in_Type_2_Diabetes_Mellitus","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/47958580/Evidence_for_Mechanistic_Alterations_of_Ca2_Homeostasis_in_Type_2_Diabetes_Mellitus"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="5" data-entity-id="14707784" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/14707784/Dual_effects_of_glucose_on_the_cytosolic_Ca2_activity_of_mouse_pancreatic_%CE%B2_cells">Dual effects of glucose on the cytosolic Ca2+ activity of mouse pancreatic β-cells</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="33661860" href="https://uppsala.academia.edu/EGylfe">E. Gylfe</a></div><p class="ds-related-work--metadata ds2-5-body-xs">1984</p><p class="ds-related-work--abstract ds2-5-body-sm">The cytosolic Ca2+ activity of mouse pancreatic &cells was studied with the intracellular fluorescent indicator quin2. When the extracellular Ca2+ concentration was 1.20 mM, the basal cytosolic Ca2+ activity was 162 + 9 nM. Stimulation with 20 mM glucose increased this Ca2+ activity by 40%. In the presence of only 0.20 mM Ca2+ or after the addition of the voltage-dependent Ca2+ -channel blocker D-600, glucose had an opposite and more prompt effect in reducing cytosolic Ca2' by about 15%. It is concluded that an early result of glucose exposure is a lowering of the cytosolic Ca2+ activity and that this effect tends to be masked by a subsequent increase of the Ca2+ activity due to influx of Ca2+ through the voltagedependent Ca2+ channels.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Dual effects of glucose on the cytosolic Ca2+ activity of mouse pancreatic β-cells","attachmentId":43956010,"attachmentType":"pdf","work_url":"https://www.academia.edu/14707784/Dual_effects_of_glucose_on_the_cytosolic_Ca2_activity_of_mouse_pancreatic_%CE%B2_cells","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/14707784/Dual_effects_of_glucose_on_the_cytosolic_Ca2_activity_of_mouse_pancreatic_%CE%B2_cells"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="6" data-entity-id="60504045" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/60504045/Effect_of_High_Glucose_on_Basal_Intracellular_Calcium_Regulation_in_Rat_Mesangial_Cell">Effect of High Glucose on Basal Intracellular Calcium Regulation in Rat Mesangial Cell</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="5910823" href="https://independent.academia.edu/SeongHong">Seong Hong</a></div><p class="ds-related-work--metadata ds2-5-body-xs">American Journal of Nephrology, 2003</p><p class="ds-related-work--abstract ds2-5-body-sm">Background: A number of cellular mechanisms are critically dependent on intracellular Ca 2+ homeostasis. A sustained increase in the intracellular Ca 2+ concentration ([Ca 2+ ] i) is capable of activating a number of potentially harmful processes including phenotype change to secretory type, dysregulated cell proliferation, and cell injury and death. Mesangial cells (MCs) play an important role in the pathophysiology of diabetic nephropathy. Methods: We evaluated the effect of high glucose on basal [Ca 2+ ] i in the unstimulated state and identified its contributing pathways. MCs were isolated and cultured from Sprague-Dawley rats. [Ca 2+ ] i was measured by fluorometric technique with fura-2AM. Results: In a dosedependent manner, superfusion of MCs with Tyrode's solution containing high glucose (30 and 50 mM) induced a delayed spontaneous increase in [Ca 2+ ] i , which was not found in those with normal (5.5 mM) glucose or mannitol. The high glucose-induced increase in [Ca 2+ ] i occurred through transmembrane influx of extracellular Ca 2+ and was blocked by SKF96365, an inhibitor of storeoperated Ca 2+ influx. Na +-Ca 2+ exchanger (NCX) activity, a major channel regulating basal [Ca 2+ ] i , and the clearing ability of intracellular Ca 2+ were depressed after MCs were cultured in high-glucose medium. Western blot analysis revealed the decreased expression of a 70-kD NCX protein in MCs cultured in high-glucose medium. Conclusions: A high-glucose concentration induced a spontaneous increase in basal [Ca 2+ ] i of MCs without stimulation. There was a decrease in the activity of NCX in the high-glucose condition, which seems to occur at the level of protein expression. The present results provide a novel insight into the mechanisms of diabetic nephropathy in that intracellular Ca 2+ homeostasis is an important secondary messenger and a mediator in hormonal signaling.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Effect of High Glucose on Basal Intracellular Calcium Regulation in Rat Mesangial Cell","attachmentId":73920041,"attachmentType":"pdf","work_url":"https://www.academia.edu/60504045/Effect_of_High_Glucose_on_Basal_Intracellular_Calcium_Regulation_in_Rat_Mesangial_Cell","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/60504045/Effect_of_High_Glucose_on_Basal_Intracellular_Calcium_Regulation_in_Rat_Mesangial_Cell"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="7" data-entity-id="111291827" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/111291827/Evidence_for_Mechanistic_Alterations_of_mml_math_xmlns_mml_http_www_w3_org_1998_Math_MathML_id_E1_mml_msup_mml_mtext_Ca_mml_mtext_mml_mrow_mml_mn_2_mml_mn_mml_mo_mml_mo_mml_mrow_mml_msup_mml_math_Homeostasis_in_Type_2_Diabetes_Mellitus">Evidence for Mechanistic Alterations of<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="E1"><mml:msup><mml:mtext>Ca</mml:mtext><mml:mrow><mml:mn>2</mml:mn><mml:mo>+</mml:mo></mml:mrow></mml:msup></mml:math>Homeostasis in Type 2 Diabetes Mellitus</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="171302158" href="https://independent.academia.edu/BalasubramanyamMuthuswamy">Muthuswamy Balasubramanyam</a></div><p class="ds-related-work--metadata ds2-5-body-xs">International Journal of Experimental Diabetes Research, 2000</p><p class="ds-related-work--abstract ds2-5-body-sm">Altered cytosolic Ca 2+ is implicated in the aetiology of many diseases including diabetes but there are few studies on the mechanism(s) of the altered Ca 2+ regulation. Using human lymphocytes, we studied cytosolic calcium (Ca/) and various Ca 2+ transport mechanisms in subjects with Type 2 diabetes mellitus and control subjects. Ca2+-specific fluorescent probes (Fura-2 and Fluo-3) were used to monitor the Ca 2+ signals. Thapsigargin, a potent and specific inhibitor of the sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA), was used to study Ca 2+store dependent Ca 2+ fluxes. Significant (P<0.05) elevation of basal Ca/ levels was observed in lymphocytes from diabetic subjects. Ca/levels were positively corr41ted with fasting, plasma glucose and HbAlc. There was also a significant (P<0.05) reduction in plasma membrane calcium (PMCA) ATPase activity in diabetic subjects compared to controls. Cells from Type 2 diabetics exhibited an increased Ca 2+ influx (as measured both by Fluo-3 fliorescence and 45Ca assays) as a consequence of fhapsigargin-mediated Ca 2+ store depletion. Upon addition of Mn 2+ (a surrogate of Ca2+), the fura-2 fluorescence decayed in an exponential fashion and the rate and extent of this decline was steeper and greater in cells from type 2 diabetic patients. There was also a significant (P<0.05) difference in the Na+/Ca 2+ exchange activity in Type 2 diabetic patients, both under resting conditions and after challenging the cells with thapsigargin, when the internal store Ca 2+ sequestration was circumvented. Pharmacological activation of protein kinase C (PKC) in cells from patients resulted in only partial inhibition of Ca 2+ entry. We conclude that cellular Ca 2+ accumulation in cells from Type 2 diabetes results from (a) reduction in PMCA ATPase activity, (b) modulation of Na+/Ca 2+ exchange and (3) increased Ca 2+ influx across the plasma membrane.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Evidence for Mechanistic Alterations of\u003cmml:math xmlns:mml=\"http://www.w3.org/1998/Math/MathML\" id=\"E1\"\u003e\u003cmml:msup\u003e\u003cmml:mtext\u003eCa\u003c/mml:mtext\u003e\u003cmml:mrow\u003e\u003cmml:mn\u003e2\u003c/mml:mn\u003e\u003cmml:mo\u003e+\u003c/mml:mo\u003e\u003c/mml:mrow\u003e\u003c/mml:msup\u003e\u003c/mml:math\u003eHomeostasis in Type 2 Diabetes Mellitus","attachmentId":108870475,"attachmentType":"pdf","work_url":"https://www.academia.edu/111291827/Evidence_for_Mechanistic_Alterations_of_mml_math_xmlns_mml_http_www_w3_org_1998_Math_MathML_id_E1_mml_msup_mml_mtext_Ca_mml_mtext_mml_mrow_mml_mn_2_mml_mn_mml_mo_mml_mo_mml_mrow_mml_msup_mml_math_Homeostasis_in_Type_2_Diabetes_Mellitus","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/111291827/Evidence_for_Mechanistic_Alterations_of_mml_math_xmlns_mml_http_www_w3_org_1998_Math_MathML_id_E1_mml_msup_mml_mtext_Ca_mml_mtext_mml_mrow_mml_mn_2_mml_mn_mml_mo_mml_mo_mml_mrow_mml_msup_mml_math_Homeostasis_in_Type_2_Diabetes_Mellitus"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="8" data-entity-id="33099073" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/33099073/Measurements_of_cytoplasmic_free_Ca2_concentration_in_human_pancreatic_islets_and_insulinoma_cells">Measurements of cytoplasmic free Ca2+ concentration in human pancreatic islets and insulinoma cells</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="64502272" href="https://independent.academia.edu/PerArkhammar">Per Arkhammar</a></div><p class="ds-related-work--metadata ds2-5-body-xs">FEBS Letters, 1991</p><p class="ds-related-work--abstract ds2-5-body-sm">In human pdncredtic islets an increase m the glucose concentrntlon from 3 lo 20 mM rdised the free cytoplasnnc Ca" concentration ([Ca"],), an effect being reversible upon wlthdrdwdl of the sugar Dcpolarlzdtion with a high conccnlration of K' or the sulphonylurcd tolbutamlde also raised [@*I, Addltlon of extracellular ATP produced a transient rapld rise m [Ca"], Oscdlatlons m [Ca"'], were observed m the presence of IO mM glucose Insulmoma cells responded to glucose and tolbutamlde with mcrcases m [Cd"], whereas the sulphonamlde dlazoxtde caused a decrease m [Ca"], These findings confirm previous results obtained m rodent p-cells Human pancredtic islet, Human msulinoma. Cytoplasmlc free Ca" concentrdtlon. Furd-2</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Measurements of cytoplasmic free Ca2+ concentration in human pancreatic islets and insulinoma cells","attachmentId":53196746,"attachmentType":"pdf","work_url":"https://www.academia.edu/33099073/Measurements_of_cytoplasmic_free_Ca2_concentration_in_human_pancreatic_islets_and_insulinoma_cells","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/33099073/Measurements_of_cytoplasmic_free_Ca2_concentration_in_human_pancreatic_islets_and_insulinoma_cells"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="9" data-entity-id="17458708" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/17458708/Ca2_Secretion_Coupling_Is_Impaired_in_Diabetic_Goto_Kakizaki_rats">Ca2+-Secretion Coupling Is Impaired in Diabetic Goto Kakizaki rats</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="37201832" href="https://meduniwien.academia.edu/MarjanSlakRupnik">Marjan Slak Rupnik</a></div><p class="ds-related-work--metadata ds2-5-body-xs">The Journal of General Physiology, 2007</p><p class="ds-related-work--abstract ds2-5-body-sm">The Goto Kakizaki (GK) rat is a widely used animal model to study defective glucose-stimulated insulin release in type-2 diabetes (T2D). As in T2D patients, the expression of several proteins involved in Ca 2+ -dependent exocytosis of insulin-containing large dense-core vesicles is dysregulated in this model. So far, a defect in late steps of insulin secretion could not be demonstrated. To resolve this apparent contradiction, we studied Ca 2+ -secretion coupling of healthy and GK rat β cells in acute pancreatic tissue slices by assessing exocytosis with high time-resolution membrane capacitance measurements. We found that β cells of GK rats respond to glucose stimulation with a normal increase in the cytosolic Ca 2+ concentration. During trains of depolarizing pulses, the secretory activity from GK rat β cells was defective in spite of upregulated cell size and doubled voltage-activated Ca 2+ currents. In GK rat β cells, evoked Ca 2+ entry was signifi cantly less effi cient in triggering release than in nondiabetic controls. This impairment was neither due to a decrease of functional vesicle pool sizes nor due to different kinetics of pool refi lling. Strong stimulation with two successive trains of depolarizing pulses led to a prominent activity-dependent facilitation of release in GK rat β cells, whereas secretion in controls was unaffected. Broad-spectrum inhibition of PKC sensitized Ca 2+ -dependent exocytosis, whereas it prevented the activity-dependent facilitation in GK rat β cells. We conclude that a decrease in the sensitivity of the GK rat β-cell to depolarization-evoked Ca 2+ infl ux is involved in defective glucose-stimulated insulin secretion. Furthermore, we discuss a role for constitutively increased activity of one or more PKC isoenzymes in diabetic rat β cells.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Ca2+-Secretion Coupling Is Impaired in Diabetic Goto Kakizaki rats","attachmentId":39519858,"attachmentType":"pdf","work_url":"https://www.academia.edu/17458708/Ca2_Secretion_Coupling_Is_Impaired_in_Diabetic_Goto_Kakizaki_rats","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/17458708/Ca2_Secretion_Coupling_Is_Impaired_in_Diabetic_Goto_Kakizaki_rats"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div></div></div><div class="ds-sticky-ctas--wrapper js-loswp-sticky-ctas hidden"><div class="ds-sticky-ctas--grid-container"><div class="ds-sticky-ctas--container"><button class="ds2-5-button js-swp-download-button" data-signup-modal="{"location":"continue-reading-button--sticky-ctas","attachmentId":42688934,"attachmentType":"pdf","workUrl":null}">See full PDF</button><button class="ds2-5-button ds2-5-button--secondary js-swp-download-button" data-signup-modal="{"location":"download-pdf-button--sticky-ctas","attachmentId":42688934,"attachmentType":"pdf","workUrl":null}"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">download</span>Download PDF</button></div></div></div><div class="ds-below-fold--grid-container"><div class="ds-work--container js-loswp-embedded-document"><div class="attachment_preview" data-attachment="Attachment_42688934" style="display: none"><div class="js-scribd-document-container"><div class="scribd--document-loading js-scribd-document-loader" style="display: block;"><img alt="Loading..." src="//a.academia-assets.com/images/loaders/paper-load.gif" /><p>Loading Preview</p></div></div><div style="text-align: center;"><div class="scribd--no-preview-alert js-preview-unavailable"><p>Sorry, preview is currently unavailable. You can download the paper by clicking the button above.</p></div></div></div></div><div class="ds-sidebar--container js-work-sidebar"><div class="ds-related-content--container"><h2 class="ds-related-content--heading">Related papers</h2><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="0" data-entity-id="29196421" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/29196421/The_influence_of_insulin_on_calcium_ion_concentration_during_transduction_of_signals_into_neutrophils">The influence of insulin on calcium ion concentration during transduction of signals into neutrophils</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="55108255" href="https://independent.academia.edu/PawelWinklewski">Pawel Winklewski</a></div><p class="ds-related-work--metadata 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href="https://uc-pt.academia.edu/AngeloTome">Ângelo Tomé</a></div><p class="ds-related-work--metadata ds2-5-body-xs">International Journal of Biochemistry and Cell Biology, 2000</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Glucose-mediated Ca(2+) signalling in single clonal insulin-secreting cells: evidence for a mixed model of cellular activation","attachmentId":44130748,"attachmentType":"pdf","work_url":"https://www.academia.edu/14465926/Glucose_mediated_Ca_2_signalling_in_single_clonal_insulin_secreting_cells_evidence_for_a_mixed_model_of_cellular_activation","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline 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class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="155634147" href="https://independent.academia.edu/HelenaMAXimenes">Helena M A Ximenes</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Journal of Biological …, 2003</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Opposite effects of glucose on plasma membrane Ca2+-ATPase and Na/Ca exchanger transcription, expression, and activity in rat pancreatic β-cells","attachmentId":67562245,"attachmentType":"pdf","work_url":"https://www.academia.edu/49176776/Opposite_effects_of_glucose_on_plasma_membrane_Ca2_ATPase_and_Na_Ca_exchanger_transcription_expression_and_activity_in_rat_pancreatic_%CE%B2_cells","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span 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basal GLUT1 activity and plays a permissive role in its activation by metabolic stress and insulin in rat epithelial cells</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="5920267" href="https://independent.academia.edu/OmarQuintanilla">Omar Quintanilla</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Cell Calcium, 2000</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Cytosolic [Ca 2+] modulates basal GLUT1 activity and plays a permissive role in its activation by metabolic stress and insulin in rat epithelial 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data-entity-id="86058330" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/86058330/The_cytoplasmic_Ca2_response_to_glucose_as_an_indicator_of_impairment_of_the_pancreatic_%CE%B2_cell_function">The cytoplasmic Ca2+ response to glucose as an indicator of impairment of the pancreatic β-cell function</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="146181832" href="https://independent.academia.edu/EvaGrapengiesser">Eva Grapengiesser</a></div><p class="ds-related-work--metadata ds2-5-body-xs">European Journal of Clinical Investigation, 2008</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"The cytoplasmic Ca2+ response to glucose as an indicator of impairment of 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Herchuelz</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Cell Calcium, 1990</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Effects of glucose on 45Ca2+ outflow, cytosolic Ca2+ concentration and insulin release from freshly isolated and cultured adult rat islets","attachmentId":99665241,"attachmentType":"pdf","work_url":"https://www.academia.edu/98266153/Effects_of_glucose_on_45Ca2_outflow_cytosolic_Ca2_concentration_and_insulin_release_from_freshly_isolated_and_cultured_adult_rat_islets","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" href="https://www.academia.edu/98266153/Effects_of_glucose_on_45Ca2_outflow_cytosolic_Ca2_concentration_and_insulin_release_from_freshly_isolated_and_cultured_adult_rat_islets"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="7" data-entity-id="74373263" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/74373263/High_glucose_level_inhibits_capacitative_Ca_2_influx_in_cultured_rat_mesangial_cells_by_a_protein_kinase_C_dependent_mechanism">High glucose level inhibits capacitative Ca 2 + influx in cultured rat mesangial cells by a protein kinase C-dependent mechanism</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="31697606" href="https://uniroma1.academia.edu/GPugliese">G. Pugliese</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Diabetologia, 1997</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"High glucose level inhibits capacitative Ca 2 + influx in cultured rat mesangial cells by a protein kinase C-dependent mechanism","attachmentId":82549555,"attachmentType":"pdf","work_url":"https://www.academia.edu/74373263/High_glucose_level_inhibits_capacitative_Ca_2_influx_in_cultured_rat_mesangial_cells_by_a_protein_kinase_C_dependent_mechanism","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" 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class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="160199738" href="https://independent.academia.edu/SeungRyoungJung">Seung Ryoung Jung</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Diabetologia, 2013</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Loss of coupling between calcium influx, energy consumption and insulin secretion associated with development of hyperglycaemia in the UCD-T2DM rat model of type 2 diabetes","attachmentId":103207429,"attachmentType":"pdf","work_url":"https://www.academia.edu/103113689/Loss_of_coupling_between_calcium_influx_energy_consumption_and_insulin_secretion_associated_with_development_of_hyperglycaemia_in_the_UCD_T2DM_rat_model_of_type_2_diabetes","alternativeTracking":true}"><span class="material-symbols-outlined" 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class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="48788222" href="https://iub-bd.academia.edu/shahidulislam">shahidul islam</a></div><p class="ds-related-work--metadata ds2-5-body-xs">FEBS Letters, 1992</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Ca2+-induced Ca2+ release in insulin-secreting cells","attachmentId":45739201,"attachmentType":"pdf","work_url":"https://www.academia.edu/25422358/Ca2_induced_Ca2_release_in_insulin_secreting_cells","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" 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ds2-5-body-xs">Diabetes, 2000</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Glucose-induced [Ca2+]i abnormalities in human pancreatic islets: important role of overstimulation","attachmentId":101813234,"attachmentType":"pdf","work_url":"https://www.academia.edu/101209982/Glucose_induced_Ca2_i_abnormalities_in_human_pancreatic_islets_important_role_of_overstimulation","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" href="https://www.academia.edu/101209982/Glucose_induced_Ca2_i_abnormalities_in_human_pancreatic_islets_important_role_of_overstimulation"><span class="ds2-5-text-link__content">View PDF</span><span 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Herchuelz</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Biochimica et Biophysica Acta (BBA) - Biomembranes, 1983</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Activation, but not inhibition, by glucose of Ca2+-dependent K+ permeability in the rat pancreatic B-cell","attachmentId":87780396,"attachmentType":"pdf","work_url":"https://www.academia.edu/81896710/Activation_but_not_inhibition_by_glucose_of_Ca2_dependent_K_permeability_in_the_rat_pancreatic_B_cell","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" 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class="ds-related-work--metadata ds2-5-body-xs">Kidney International, 1993</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"High glucose inhibits cytosolic calcium signaling in cultured rat mesangial cells","attachmentId":113313731,"attachmentType":"pdf","work_url":"https://www.academia.edu/117463092/High_glucose_inhibits_cytosolic_calcium_signaling_in_cultured_rat_mesangial_cells","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" href="https://www.academia.edu/117463092/High_glucose_inhibits_cytosolic_calcium_signaling_in_cultured_rat_mesangial_cells"><span class="ds2-5-text-link__content">View PDF</span><span 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href="https://independent.academia.edu/AHerchuelz">A. Herchuelz</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Cell Calcium, 1991</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Heterogeneous changes in [Ca2+]i induced by glucose, tolbutamide and K+ in single rat pancreatic B cells","attachmentId":87780394,"attachmentType":"pdf","work_url":"https://www.academia.edu/81896726/Heterogeneous_changes_in_Ca2_i_induced_by_glucose_tolbutamide_and_K_in_single_rat_pancreatic_B_cells","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" 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