Aims/hypothesis: Insulin resistance leads to oxidative stress and cardiac dysfunction. This study examined the impact of catalase on insulin-resistance-induced cardiac dysfunction, oxidative damage and insulin sensitivity.
Methods: Insulin resistance was initiated in FVB and catalase-transgenic mice by 12 weeks of sucrose feeding. Contractile and intracellular Ca2+ properties were evaluated in cardiomyocytes including peak shortening (PS), time-to-PS (TPS), time-to-90% relengthening (TR90), half-width duration (HWD), maximal velocity of shortening/relengthening (+/-dL/dt), fura-fluorescence intensity change (DeltaFFI) and intracellular Ca2+ clearance rate (tau). Reactive oxygen species (ROS) and protein damage were evaluated with dichlorodihydrofluorescein and protein carbonyl formation.
Results: Sucrose-fed mice displayed hyperinsulinaemia, impaired glucose tolerance and normal body weight. Myocytes from FVB sucrose-fed mice exhibited depressed PS and +/-dL/dt, prolonged TR90 and tau, and reduced DeltaFFI associated with normal TPS and HWD compared with those from starch-fed control mice. ROS and protein carbonyl formation were elevated in FVB sucrose-fed mice. Insulin sensitivity was reduced, evidenced by impaired insulin-stimulated 2-deoxy-D: -[3H]glucose uptake. Western blot analysis indicated that sucrose feeding: (1) inhibited insulin-stimulated phosphorylation of insulin receptor and Akt; (2) enhanced protein-tyrosine phosphatase 1B (PTP1B) expression; and (3) suppressed endothelial nitric oxide synthase (eNOS) and Na+-Ca2+ exchanger expression without affecting peroxisome proliferator-activated receptor gamma (PPARgamma), sarco(endo)plasmic reticulum Ca2+-ATPase isozyme 2a and phospholamban. Catalase ablated insulin-resistance-induced mechanical dysfunction, ROS production and protein damage, and reduced eNOS, but not insulin insensitivity. Catalase itself decreased resting FFI and enhanced expression of PTP1B and PPARgamma.
Conclusions/interpretation: These data indicate that catalase rescues insulin-resistance-induced cardiac dysfunction related to ROS production and protein oxidation but probably does not improve insulin sensitivity.