期刊
DIABETES & VASCULAR DISEASE RESEARCH
卷 14, 期 5, 页码 423-433出版社
SAGE PUBLICATIONS LTD
DOI: 10.1177/1479164117710390
关键词
Diabetes; diabetic cardiomyopathy; insulin; diastolic dysfunction; cardiac remodelling; myocardial inflammation
资金
- Diabetes Australia
- Victorian Government of Australia's Operational Infrastructure Support Program
- National Health and Medical Research Council (NHMRC) of Australia [ID1059960, ID1059660]
- Career Development Fellowship from the NHMRC
- Heart Foundation (of Australia) Future Leader Fellowship
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.
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