AIMS/HYPOTHESIS: Diabetic cardiomyopathy (DCM) is common in type 2 diabetes. In DCM, insulin resistance may alter cardiac substrate supply and utilisation leading to changes in myocardial metabolism and cardiac function. In rats, exposure to excessive alimentary fat, inducing a type 2 diabetic phenotype, may result in myocardial insulin resistance and cardiac functional changes resembling DCM. MATERIALS AND METHODS: Rats received high-fat (HFD) or low-fat (LFD) diets for 7 weeks. Prior to killing, insulin or saline was injected i.p. Contractile function and insulin signalling were assessed in papillary muscles and ventricular lysates, respectively. RESULTS: Fasting and post-load blood glucose levels were increased in HFD- vs LFD-rats (all p < 0.02). Mean heart weight, but not body weight, was increased in HFD-rats (p < 0.01). HFD-hearts showed structural changes and triglyceride accumulation. HFD-muscles developed higher baseline and maximum forces, but showed impaired recovery from higher workloads. Insulin-associated modulation of Ca2+-induced force augmentation was abolished in HFD-muscles. HFD reduced insulin-stimulated IRS1-associated phosphatidylinositol 3'-kinase activity and phosphorylation of protein kinase B, glycogen synthase kinase-3beta, endothelial nitric oxide synthase, and forkhead transcription factors by 40-60% (all p < 0.05). Insulin-mediated phosphorylation of phospholamban, a critical regulator of myocardial contractility, was decreased in HFD-hearts (p < 0.05). CONCLUSIONS/ INTERPRETATION: HFD induced a hypertrophy-like cardiac phenotype, characterised by a higher basal contractile force, an impaired recovery from increased workloads and decreased insulin-mediated protection against Ca2+ overload. Cardiac dysfunction was associated with myocardial insulin resistance and phospholamban hypophosphorylation. Our data suggest that myocardial insulin resistance, resulting from exposure to excessive alimentary fat, may contribute to the pathogenesis of diabetes-related heart disease.
AIMS/HYPOTHESIS: Diabetic cardiomyopathy (DCM) is common in type 2 diabetes. In DCM, insulin resistance may alter cardiac substrate supply and utilisation leading to changes in myocardial metabolism and cardiac function. In rats, exposure to excessive alimentary fat, inducing a type 2 diabetic phenotype, may result in myocardial insulin resistance and cardiac functional changes resembling DCM. MATERIALS AND METHODS:Rats received high-fat (HFD) or low-fat (LFD) diets for 7 weeks. Prior to killing, insulin or saline was injected i.p. Contractile function and insulin signalling were assessed in papillary muscles and ventricular lysates, respectively. RESULTS: Fasting and post-load blood glucose levels were increased in HFD- vs LFD-rats (all p < 0.02). Mean heart weight, but not body weight, was increased in HFD-rats (p < 0.01). HFD-hearts showed structural changes and triglyceride accumulation. HFD-muscles developed higher baseline and maximum forces, but showed impaired recovery from higher workloads. Insulin-associated modulation of Ca2+-induced force augmentation was abolished in HFD-muscles. HFD reduced insulin-stimulated IRS1-associated phosphatidylinositol 3'-kinase activity and phosphorylation of protein kinase B, glycogen synthase kinase-3beta, endothelial nitric oxide synthase, and forkhead transcription factors by 40-60% (all p < 0.05). Insulin-mediated phosphorylation of phospholamban, a critical regulator of myocardial contractility, was decreased in HFD-hearts (p < 0.05). CONCLUSIONS/ INTERPRETATION: HFD induced a hypertrophy-like cardiac phenotype, characterised by a higher basal contractile force, an impaired recovery from increased workloads and decreased insulin-mediated protection against Ca2+ overload. Cardiac dysfunction was associated with myocardial insulin resistance and phospholamban hypophosphorylation. Our data suggest that myocardial insulin resistance, resulting from exposure to excessive alimentary fat, may contribute to the pathogenesis of diabetes-related heart disease.
Authors: M F Allard; R B Wambolt; S L Longnus; M Grist; C P Lydell; H L Parsons; B Rodrigues; J L Hall; W C Stanley; G P Bondy Journal: Am J Physiol Endocrinol Metab Date: 2000-09 Impact factor: 4.310
Authors: Regis R Lamberts; Mattie H P Van Rijen; Pieter Sipkema; Paul Fransen; Stanislas U Sys; Nico Westerhof Journal: Am J Physiol Heart Circ Physiol Date: 2002-10 Impact factor: 4.733
Authors: Sihem Boudina; Heiko Bugger; Sandra Sena; Brian T O'Neill; Vlad G Zaha; Olesya Ilkun; Jordan J Wright; Pradip K Mazumder; Eric Palfreyman; Timothy J Tidwell; Heather Theobald; Oleh Khalimonchuk; Benjamin Wayment; Xiaoming Sheng; Kenneth J Rodnick; Ryan Centini; Dong Chen; Sheldon E Litwin; Bart E Weimer; E Dale Abel Journal: Circulation Date: 2009-02-23 Impact factor: 29.690
Authors: Gábor Koncsos; Zoltán V Varga; Tamás Baranyai; Kerstin Boengler; Susanne Rohrbach; Ling Li; Klaus-Dieter Schlüter; Rolf Schreckenberg; Tamás Radovits; Attila Oláh; Csaba Mátyás; Árpád Lux; Mahmoud Al-Khrasani; Tímea Komlódi; Nóra Bukosza; Domokos Máthé; László Deres; Monika Barteková; Tomáš Rajtík; Adriana Adameová; Krisztián Szigeti; Péter Hamar; Zsuzsanna Helyes; László Tretter; Pál Pacher; Béla Merkely; Zoltán Giricz; Rainer Schulz; Péter Ferdinandy Journal: Am J Physiol Heart Circ Physiol Date: 2016-08-12 Impact factor: 4.733
Authors: Jordan J Wright; Jaetaek Kim; Jonathan Buchanan; Sihem Boudina; Sandra Sena; Kyriaki Bakirtzi; Olesya Ilkun; Heather A Theobald; Robert C Cooksey; Kostantin V Kandror; E Dale Abel Journal: Cardiovasc Res Date: 2009-01-15 Impact factor: 10.787
Authors: Jian Liu; Peipei Wang; Samuel L Douglas; Joshua M Tate; Simon Sham; Steven G Lloyd Journal: Am J Physiol Heart Circ Physiol Date: 2016-05-06 Impact factor: 4.733