{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T20:38:34Z","timestamp":1779223114230,"version":"3.51.4"},"reference-count":40,"publisher":"Georg Thieme Verlag KG","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Exp Clin Endocrinol Diabetes"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Background Human glucagon-like peptide-1 analogue, Liraglutide, has shown cardioprotective effects in animal and clinical studies of type 2 diabetes mellitus. This study was conducted to assess the effect of Liraglutide on diabetes-induced myocardial electrical remodeling.<\/jats:p><jats:p>Materials and Methods A rat model of type 2 diabetes mellitus was induced by high-fat diet and low dose Streptozotocin (35 mg\/kg). Diabetic rats were randomized into 4 subgroups (n=6\u20137): diabetic-untreated, diabetics treated with Liraglutide, diabetics treated with Ramipril, and diabetics treated with Metformin in addition to a control group. Changes in serum glucose, insulin, lipid profile and revised quantitative insulin sensitivity check index (QUICKI index) were assessed. QT and QTc intervals were measured and the degree of cardiac interstitial and perivascular fibrosis was examined. The expression of myocardial Ito channel \u03b1 subunits, gap junction protein; Kv 4.2\/4.3 and connexin 43 (Cx43) respectively, were assessed by western blotting and immunohistochemistry.<\/jats:p><jats:p>Results Similar to Ramipril, both Liraglutide and Metformin effectively inhibited the diabetes-induced myocardial hypertrophy and fibrosis. However, Liraglutide treatment significantly improved Kv 4.2\/4.3 and Cx43 expression\/distribution and prevented diabetes-related QTc interval prolongation.<\/jats:p><jats:p>Conclusions We have shown that pathological alterations in myocardial Cx43 expression and distribution, in addition to reduced Ito channel expression, may underlie the QTc interval prolongation in high-fat diet\/STZ rat model of type 2 diabetes mellitus. The beneficial effects of Liraglutide, as those of Ramipril, on cardiac electrophysiology could be at least attributed to its direct ability to normalize expression and distribution of Cx43 and Ito channels in the diabetic rat heart.<\/jats:p>","DOI":"10.1055\/a-1162-8196","type":"journal-article","created":{"date-parts":[[2020,6,19]],"date-time":"2020-06-19T23:18:06Z","timestamp":1592608686000},"page":"899-907","source":"Crossref","is-referenced-by-count":9,"title":["Liraglutide Effect on Ventricular Transient Outward K\u2009+\u2009 Channel and Connexin-43 Protein Expression"],"prefix":"10.1055","volume":"129","author":[{"given":"Nehal M.","family":"Ramadan","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Mansoura University, Faculty of Medicine, Mansoura, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hala Abdel","family":"Malek","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Mansoura University, Faculty of Medicine, Mansoura, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karawan Abd-el","family":"Rahman","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Mansoura University, Faculty of Medicine, Mansoura, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elhamy","family":"El-Kholy","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Mansoura University, Faculty of Medicine, Mansoura, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dalia","family":"Shaalan","sequence":"additional","affiliation":[{"name":"Departments of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Mansoura University, Mansoura, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wagdi","family":"Elkashef","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine, Mansoura University, Mansoura, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2020,6,19]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1111\/j.1745-7254.2005.00146.x","article-title":"Oxidative stress and stress signaling: Menace of diabetic cardiomyopathy","volume":"26","author":"L E Wold","year":"2005","journal-title":"Acta Pharmacol Sin"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"1944","DOI":"10.1124\/dmd.110.034066","article-title":"Metabolism and excretion of the once-daily human glucagon-like peptide-1 analog liraglutide in healthy male subjects and its in vitro degradation by dipeptidyl peptidase iv and neutral endopeptidase","volume":"38","author":"M Malm-Erjef\u00e4lt","year":"2010","journal-title":"DMD"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"975","DOI":"10.2337\/db08-1193","article-title":"GLP-1R agonist liraglutide activates cytoprotective pathways and improves 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