دورية أكاديمية

Glucagon-Like Peptide-1 Protects Against Cardiac Microvascular Injury in Diabetes via a cAMP/PKA/Rho-Dependent Mechanism.

التفاصيل البيبلوغرافية
العنوان: Glucagon-Like Peptide-1 Protects Against Cardiac Microvascular Injury in Diabetes via a cAMP/PKA/Rho-Dependent Mechanism.
المؤلفون: Dongjuan Wang, Peng Luo, Yabin Wang, Weijie Li, Chen Wang, Dongdong Sun, Rongqing Zhang, Tao Su, Xiaowei Ma, Chao Zeng, Haichang Wang, Jun Ren, Feng Cao
المصدر: Diabetes; May2013, Vol. 62 Issue 5, p1697-1708, 12p, 5 Color Photographs, 2 Black and White Photographs, 2 Charts
مصطلحات موضوعية: DIABETES complications, GLUCAGON-like peptides, STREPTOZOTOCIN, LABORATORY rats, REACTIVE oxygen species, OXIDATIVE stress
مستخلص: Impaired cardiac microvascular function contributes to cardiovascular complications in diabetes. Glucagon-like peptide-1 (GLP-1) exhibits potential cardioprotective properties in addition to its glucose-lowering effect. This study was designed to evaluate the impact of GLP-1 on cardiac microvascular injury in diabetes and the underlying mechanism involved. Experimental diabetes was induced using streptozotocin in rats. Cohorts of diabetic rats received a 12-week treatment of vildagliptin (dipeptidyl peptidase-4 inhibitor) or exenatide (GLP-1 analog). Experimental diabetes attenuated cardiac function, glucose uptake, and microvascular barrier function, which were significantly improved by vildagliptin or exenatide treatment. Cardiac microvascular endothelial cells (CMECs) were isolated and cultured in normal or high glucose medium with or without GLP-1. GLP-1 decreased high-glucose-induced reactive oxygen species production and apoptotic index, as well as the levels of NADPH oxidase such as p47phox and gp91phox. Furthermore, cAMP/PKA (cAMP-dependent protein kinase activity) was increased and Rho-expression was decreased in high-glucose-induced CMECs after GLP-1 treatment. In conclusion, GLP-1 could protect the cardiac microvessels against oxidative stress, apoptosis, and the resultant microvascular barrier dysfunction in diabetes, which may contribute to the improvement of cardiac function and cardiac glucose metabolism in diabetes. The protective effects of GLP-1 are dependent on downstream inhibition of Rho through a cAMP/PKA-mediated pathway. [ABSTRACT FROM AUTHOR]
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قاعدة البيانات: Complementary Index
الوصف
تدمد:00121797
DOI:10.2337/db12-1025