Type 2 diabetes mellitus in obesity promotes prolongation of cardiomyocyte contractile function, impaired Ca2+ handling and protein carbonylation damage

• Published in: Journal of diabetes and its complications 2023-08, Vol.37 (8), p.108559-108559, Article 108559
• Main Authors: Coelho, Priscila M., Simmer, Luísa M., da Silva, Daniel S., dos Santos, Matheus C., Kitagawa, Rodrigo R., Pezzin, Mateus F., Correa, Camila R., Leite, Jéssica G., Leopoldo, André S., Lima-Leopoldo, Ana Paula
• Format: Article
• Language: English
• Subjects: Calcium handling; Contractile function; Oxidative stress; Type 2 diabetes mellitus in obesity
• ISSN: 1056-8727; 1873-460X
• DOI: 10.1016/j.jdiacomp.2023.108559

To investigate whether the obesity associated to T2DM presented cardiomyocyte myocardial contractility dysfunction due to damage in Ca2+ handling, concomitantly with increased biomarkers of oxidative stress. Male Wistar rats were randomized into two groups: control (C): fed with standard diet; and obese (Ob) that fed a saturated high-fat. After the characterization of obesity (12 weeks), the Ob animals were submitted to T2DM induction with a single dose of intraperitoneal (i.p.) injection of streptozotocin (30 mg/kg). Thus, remained Ob rats that were characterized as to the presence (T2DMOb; n = 8) and/or absence (Ob; n = 10) of T2DM. Cardiac remodeling was measured by post-mortem morphological, isolated cardiomyocyte contractile function, as well as by intracellular Ca2+-handling analysis. T2DMOb presented a significant reduction of all fat pads, total body fat and adiposity index. T2DMOb group presented a significant increase in protein carbonylation and superoxide dismutase (SOD) activity, respectively. T2DMOb promoted elevations in fractional shortening (15.6 %) and time to 50 % shortening (5.8 %), respectively. Time to 50 % Ca2+ decay was prolonged in T2DMOb, suggesting a possible impairment in Ca2+recapture and/or removal. Type 2 diabetes mellitus in obesity promotes prolongation of cardiomyocyte contractile function with protein carbonylation damage and impaired Ca2+ handling. •Overweight and obesity are important risk factors for the T2DM development•Oxidative stress, and its implications for excitation–contraction coupling•Increased reactive oxygen species in obesity can contribute to Ca2+ handling damage and cardiac dysfunction