{"id":15566,"date":"2024-08-01T08:04:54","date_gmt":"2024-08-01T08:04:54","guid":{"rendered":"https:\/\/www.nanion.de\/?post_type=resource_library&#038;p=15566"},"modified":"2024-08-01T08:04:54","modified_gmt":"2024-08-01T08:04:54","slug":"2024-preclinical-models-of-glycaemic-variability-recapitulate-clinical-cardiovascular-outcomes-in-diabetes","status":"publish","type":"resource_library","link":"https:\/\/nanion.com\/ja\/resource_library\/2024-preclinical-models-of-glycaemic-variability-recapitulate-clinical-cardiovascular-outcomes-in-diabetes\/","title":{"rendered":"2024 &#8211; Preclinical models of Glycaemic variability recapitulate Clinical Cardiovascular outcomes in Diabetes"},"content":{"rendered":"<section id=\"sec1\" tabindex=\"0\" data-locator=\"sec1\">\n<p id=\"secsectitle0010\" class=\"top\" tabindex=\"-1\" data-left-hand-nav=\"Introduction\"><span class=\"top__text\">Introduction<\/span><\/p>\n<p class=\"section-paragraph\">Heart disease is the most prevalent cause of morbidity and mortality in people living with diabetes. Diabetes increases the risk of heart disease two-fold, due largely to risks associated with ischaemic injuries such as myocardial infarction (MI). This study develops preclinical co-morbidity models to study mechanisms of ischaemia sensitivity in diabetes.<\/p>\n<\/section>\n<p id=\"secsectitle0015\" class=\"top\" tabindex=\"-1\" data-left-hand-nav=\"Methods &amp; Results\"><span class=\"top__text\">Methods &amp; Results<\/span><\/p>\n<div class=\"section-paragraph\">First, we use human-induced pluripotent stem cell-derived cardiomyocytes to optimise conditions for modelling ischaemia-reperfusion injury in vitro. Cross-comparison of molecular phenotyping, statistical genetics, and cell physiology identify a backbone of fatty acid conditions optimal for ischaemia disease modelling. We next adapt these conditions for modelling glycaemic stress in diabetes. Patients with diabetes are exposed to frequent and higher magnitude postprandial glucose spikes. Compared to control and constant glycaemic stress<em>,<\/em>\u00a0we found that variable glycaemic stress resulted in more significant contractile deficits, severe metabolic reprogramming, and increased susceptibility to post-ischaemic cell death. We next adapted these findings for in vivo modelling using a high-fat diet-induced mouse model of diabetes. Similar to in vitro modelling results, animals exposed to variable glycaemic stress showed significant functional deficits and increased post-MI mortality. A meta-analysis of epidemiological studies demonstrates a close alignment of these preclinical models with cardiovascular outcomes of patients with diabetes.<\/div>\n<section id=\"sec3\" tabindex=\"0\" data-locator=\"sec3\">\n<p id=\"secsectitle0020\" class=\"top\" tabindex=\"-1\" data-left-hand-nav=\"Conclusion\"><span class=\"top__text\">Conclusion<\/span><\/p>\n<p class=\"section-paragraph\">Taken together, these novel pre-clinical models provide new opportunities to study disease mechanisms of ischaemia and diabetes and identify glycaemic variability as a major risk factor for myocardial injury in diabetes.<\/p>\n<\/section>\n","protected":false},"featured_media":0,"template":"","products_tags":[34],"resource_type":[75],"application_areas":[53,76,77],"therapeutic_areas":[54,143],"target_categories":[],"target_families":[],"targets":[],"resource_keyword":[],"class_list":["post-15566","resource_library","type-resource_library","status-publish","hentry","products_tags-cardioexcyte-96","resource_type-publication","application_areas-assay-development-and-validation","application_areas-drug-discovery","application_areas-cell-ipscs-profiling","therapeutic_areas-cardiac-safety-cipa","therapeutic_areas-assay-development-and-validation"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_library\/15566","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_library"}],"about":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/types\/resource_library"}],"wp:attachment":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/media?parent=15566"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/products_tags?post=15566"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_type?post=15566"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/application_areas?post=15566"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/therapeutic_areas?post=15566"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_categories?post=15566"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_families?post=15566"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/targets?post=15566"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_keyword?post=15566"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}