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Effects of exercise training combined with insulin treatment on cardiac NOS1 signaling pathways in type 1 diabetic rats

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Abstract

This study examined the effects of a dual treatment combining insulin treatment and exercise training on basal cardiac function and signaling pathways involving β3-AR, NOS1, and RyR2 in type 1 diabetic rats. Male Wistar rats were assigned into a diabetic group receiving no treatment (D), an insulin-treated diabetic (Ins), a trained diabetic (TD), and a trained insulin-treated diabetic (TIns) group. Control group (C) was included in order to confirm the deleterious effects of diabetes. Insulin treatment and/or treadmill exercise training were conducted for 8 weeks. Basal cardiac function was evaluated by Langendorff technique. Cardiac protein expression of β3-AR, NOS1, and RyR2 was assessed using Western blots. Diabetes induced a decrease of both basal diastolic and systolic (±dP/dt) cardiac function (P < 0.05). Moreover, diabetes was associated with an increase of β3-AR and NOS1 and a decrease of RyR2 expression (P < 0.05). Although combined treatment was not able to normalize –dP/dt, it succeeded to normalize +dP/dt of diabetic rats. Combined treatment led to an overexpression of RyR2. Effects of this combined treatment on +dP/dt and RyR2 were greater than the effects of insulin and exercise training, applied solely. Treatments, applied solely or in combination, resulted in a complete normalization of β3-AR and in a down-regulation of NOS1 because this protein expression in all treated diabetic rats became lower than control values (P < 0.01). Our study shows that unlike single treatments, dual treatment combining insulin treatment and exercise training was able to normalize basal systolic function of diabetic rats by a specific regulation of β3-AR–NOS1–RyR2 signaling pathways.

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Acknowledgments

We gratefully thank Pr François Carré and Pr Eric Bellisant for their hospitality, and the Biostatistical PhD Audrey Lavenu for her statistical assistance, from the laboratory of Pharmacology (Faculty of Medicine, Rennes 1). We thank Mrs. Catherine Lemeslif and Christine Dutais from the laboratory of Medical Physiology (Faculty of Medicine, Rennes 1) for their technical assistance. We also thank Dawn C. Harrison and Will Loh (School of Clinical Sciences, University of Liverpool, UK) for their helpful advice for the English translation.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Laboratory Movement Sport and Health Sciences, UFR APS, University of Rennes 2, Avenue Charles Tillon, 35044, Rennes cedex, France

    Solène Le Douairon Lahaye, Amélie Rebillard, Mohamed Sami Zguira, Ludivine Malardé, Bernard Saïag, Arlette Gratas-Delamarche & Françoise Rannou Bekono

  2. INSERM, U642, Department of Biology and Sports Medicine Service of Functional Explorations, University of Rennes 1, LTSI; INSERM-CIC-IT 804, CHU Rennes, Rennes, France

    François Carré

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  1. Solène Le Douairon Lahaye
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  2. Amélie Rebillard
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Correspondence to Solène Le Douairon Lahaye.

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Le Douairon Lahaye, S., Rebillard, A., Zguira, M.S. et al. Effects of exercise training combined with insulin treatment on cardiac NOS1 signaling pathways in type 1 diabetic rats. Mol Cell Biochem 347, 53–62 (2011). https://doi.org/10.1007/s11010-010-0611-6

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