Journal
CARDIOVASCULAR DIABETOLOGY
Volume 12, Issue -, Pages -Publisher
BMC
DOI: 10.1186/1475-2840-12-19
Keywords
Diabetic cardiomyopathy; Arrhythmia; Lipotoxicity; Conduction velocity; Gap junctions; Type 2 diabetes; Zucker Diabetic Fatty (ZDF) rats
Funding
- Danish National Research Foundation
- Novo-Nordisk Foundation
- A.P. Moller Foundation for the Advancement of Medical Science
- Danish Council for Independent Research
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Background: Diabetes increases the risk of cardiovascular complications including arrhythmias, but the underlying mechanisms remain to be established. Decreased conduction velocity (CV), which is an independent risk factor for re-entry arrhythmias, is present in models with streptozotocin (STZ) induced type 1 diabetes. Whether CV is also disturbed in models of type 2 diabetes is currently unknown. Methods: We used Zucker Diabetic Fatty (ZDF) rats, as a model of type 2 diabetes, and their lean controls Zucker Diabetic Lean (ZDL) rats to investigate CV and its response to the anti-arrhythmic peptide analogue AAP10. Gap junction remodeling was examined by immunofluorescence and western blotting. Cardiac histomorphometry was examined by Masson's Trichrome staining and intracellular lipid accumulation was analyzed by Bodipy staining. Results: CV was significantly slower in ZDF rats (56 +/- 1.9 cm/s) compared to non-diabetic controls (ZDL, 66 +/- 1.6 cm/s), but AAP10 did not affect CV in either group. The total amount of Connexin43 (Cx43) was identical between ZDF and ZDL rats, but the amount of lateralized Cx43 was significantly increased in ZDF rats (42 +/- 12 %) compared to ZDL rats (30 +/- 8%), p<0.04. Judged by electrophoretic mobility, Cx43 phosphorylation was unchanged between ZDF and ZDL rats. Also, no differences in cardiomyocyte size or histomorphometry including fibrosis were observed between groups, but the volume of intracellular lipid droplets was 4.2 times higher in ZDF compared to ZDL rats (p<0.01). Conclusion: CV is reduced in type 2 diabetic ZDF rats. The CV disturbance may be partly explained by increased lateralization of Cx43, but other factors are likely also involved. Our data indicates that lipotoxicity potentially may play a role in development of conduction disturbances and arrhythmias in type 2 diabetes.
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