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Title: | Insulin replacement limits progression of diabetic cardiomyopathy in the low-dose streptozotocin-induced diabetic rat. | Authors: | Dusting G.J.;Cao A.H.;Hood S.G.;Huynh K.;Kiriazis H.;Du X.-J.;Julius T.L.;Figtree G.A.;Kaye D.M.;Ritchie R.H.;Tate M.;Deo M. | Institution: | (Tate, Deo, Cao, Huynh, Julius, Ritchie) Heart Failure Pharmacology Laboratory, Baker IDI Heart, Diabetes Institute, PO Box 6492, Melbourne, VIC 3004, Australia (Cao) Centre for Inflammatory Diseases, Monash University, Monash Medical Centre, Clayton, VIC, Australia (Hood) Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia (Kiriazis, Du) Experimental Cardiology Laboratory, Baker IDI Heart, Diabetes Institute, Melbourne, VIC, Australia (Figtree) North Shore Heart Research Group, Kolling Institute, University of Sydney, Sydney, NSW, Australia (Dusting) Centre for Eye Research Australia, University of Melbourne, East Melbourne, VIC, Australia (Kaye) Heart Failure Research Group, Baker IDI Heart, Diabetes Institute, Melbourne, VIC, Australia (Kaye, Ritchie) Department of Medicine, Monash University, Clayton, VIC, Australia | Issue Date: | 29-Sep-2017 | Copyright year: | 2017 | Publisher: | SAGE Publications Ltd (E-mail: info@sagepub.co.uk) | Place of publication: | United Kingdom | Publication information: | Diabetes and Vascular Disease Research. 14 (5) (pp 423-433), 2017. Date of Publication: 01 Sep 2017. | Journal: | Diabetes and Vascular Disease Research | Abstract: | Diabetic cardiomyopathy is a major contributor to the increasing burden of heart failure globally. Effective therapies remain elusive, in part due to the incomplete understanding of the mechanisms underlying diabetes-induced myocardial injury. The objective of this study was to assess the direct impact of insulin replacement on left ventricle structure and function in a rat model of diabetes. Male Sprague-Dawley rats were administered streptozotocin (55 mg/kg i.v.) or citrate vehicle and were followed for 8 weeks. A subset of diabetic rats were allocated to insulin replacement (6 IU/day insulin s.c.) for the final 4 weeks of the 8-week time period. Diabetes induced the characteristic systemic complications of diabetes (hyperglycaemia, polyuria, kidney hypertrophy) and was accompanied by marked left ventricle remodelling (cardiomyocyte hypertrophy, left ventricle collagen content) and diastolic dysfunction (transmitral E/A, left ventricle-dP/dt). Importantly, these systemic and cardiac impairments were ameliorated markedly following insulin replacement, and moreover, markers of the diabetic cardiomyopathy phenotype were significantly correlated with the extent of hyperglycaemia. In summary, these data suggest that poor glucose control directly contributes towards the underlying features of experimental diabetic cardiomyopathy, at least in the early stages, and that adequate replacement ameliorates this.Copyright © The Author(s) 2017. | DOI: | http://monash.idm.oclc.org/login?url=http://dx.doi.org/10.1177/1479164117710390 | Link to associated publication: | Click here for full text options | PubMed URL: | 28565941 [http://www.ncbi.nlm.nih.gov/pubmed/?term=28565941] | ISSN: | 1479-1641 | URI: | https://repository.monashhealth.org/monashhealthjspui/handle/1/38736 | Type: | Article | Subjects: | hemodynamic parameters animal experiment animal model animal tissue article controlled study *diabetic cardiomyopathy heart left ventricle dP-dt heart muscle fibrosis heart ventricle hypertrophy heart ventricle remodeling hyperglycemia kidney hypertrophy male nonhuman oxidative stress polyuria rat *streptozotocin-induced diabetes mellitus/dt [Drug Therapy] streptozotocin-induced diabetes mellitus/dt [Drug Therapy] collagen/ec [Endogenous Compound] glucose/ec [Endogenous Compound] *insulin zinc suspension/dt [Drug Therapy] *insulin zinc suspension/pd [Pharmacology] *insulin zinc suspension/sc [Subcutaneous Drug Administration] interleukin 10/ec [Endogenous Compound] interleukin 6/ec [Endogenous Compound] monocyte chemotactic protein 1/ec [Endogenous Compound] tumor necrosis factor/ec [Endogenous Compound] E A ratio heart muscle fibrosis heart ventricle hypertrophy heart ventricle remodeling hemodynamic parameters hyperglycemia kidney hypertrophy male nonhuman oxidative stress streptozotocin-induced diabetes mellitus / drug therapy *streptozotocin-induced diabetes mellitus / *drug therapy polyuria animal experiment animal model animal tissue Article controlled study *diabetic cardiomyopathy heart left ventricle dP-dt rat |
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