| First Author | Dong F | Year | 2006 |
| Journal | Diabetologia | Volume | 49 |
| Issue | 6 | Pages | 1421-33 |
| PubMed ID | 16586065 | Mgi Jnum | J:111486 |
| Mgi Id | MGI:3654213 | Doi | 10.1007/s00125-006-0230-7 |
| Citation | Dong F, et al. (2006) Cardiac overexpression of catalase rescues cardiac contractile dysfunction induced by insulin resistance: role of oxidative stress, protein carbonyl formation and insulin sensitivity. Diabetologia 49(6):1421-33 |
| abstractText | 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 Ca(2+) properties were evaluated in cardiomyocytes including peak shortening (PS), time-to-PS (TPS), time-to-90% relengthening (TR(90)), half-width duration (HWD), maximal velocity of shortening/relengthening (+/-dL/dt), fura-fluorescence intensity change (DeltaFFI) and intracellular Ca(2+) 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 TR(90) 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: -[(3)H]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(+)-Ca(2+) exchanger expression without affecting peroxisome proliferator-activated receptor gamma (PPARgamma), sarco(endo)plasmic reticulum Ca(2+)-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. |
