dc.contributor.author |
Zhang, L |
en |
dc.contributor.author |
Cannell, Mark |
en |
dc.contributor.author |
Phillips, Anthony |
en |
dc.contributor.author |
Cooper, Garth |
en |
dc.contributor.author |
Ward, Marie-Louise |
en |
dc.date.accessioned |
2012-03-14T19:34:57Z |
en |
dc.date.issued |
2008 |
en |
dc.identifier.citation |
Diabetes 57(8):2158-2166 01 Aug 2008 |
en |
dc.identifier.issn |
0012-1797 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/14346 |
en |
dc.description.abstract |
Objective: This study examines the extent to which the contractile deficit of diabetic cardiomyopathy is due to altered calcium metabolism. Methods: Measurements of isometric force and intracellular calcium ([Ca2+]i, fura-2/AM) were made in left ventricular trabeculae from streptozotocin (STZ)-induced diabetic rats and age-matched siblings. Results: At 1.5 mmol/L [Ca2+]o, 37 °C, and 5 Hz stimulation frequency, peak stress was depressed in diabetic rats (10 ±1 mN/mm2 vs 17 ±2 mN/mm2 control, P<0.05) with a slower time-to-peak stress (0.077 ±0.003s vs. 0.067 ±0.002s control, P<0.01) and time-to-90% relaxation (0.076 ±0.007s vs; 0.056 ±0.003s control, P<0.05). No difference was found between groups for either resting or peak Ca2+, but the Ca2+ transient was slower in time-to-peak (0.039 ±0.002s vs. 0.034 ±0.001s control) and decayed more slowly (time constant, 0.061 ±0.003s vs 0.049 ±0.003s control). Diabetic rats had a longer LV action potential (APD50, 0.098 ±0.005s vs. 0.062 ±0.005s control, P<0.0001). Western blotting showed that diabetic rats had a reduced expression of SERCA2a, with no difference in expression of the Na+/Ca2+-exchanger. Immunohistochemistry of LV free wall showed type I collagen was increased in diabetic rats (Diabetic: 7.1 ±0.1%; Control: 12.7 ±0.1%, P<0.01), and f-actin content reduced (Diabetic: 56.9 ±0.6%; Control: 61.7 ±0.4%, P<0.0001) with a disrupted structure. Conclusion: We find no evidence to support the idea that altered Ca2+ metabolism underlies the contractile deficit of diabetic cardiomyopathy. The slower action potential and reduced SERCA2a expression can explain the slower Ca2+ transient kinetics in diabetic rats, but not the contractile deficit. Instead, we suggest that the observed LV remodeling may play a crucial role. |
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dc.publisher |
American Diabetes Association |
en |
dc.relation.ispartofseries |
Diabetes |
en |
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. Details obtained from: http://www.sherpa.ac.uk/romeo/issn/0012-1797/ |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.title |
'Altered calcium homeostasis fails to explain the contractile deficit of diabetic cardiomyopthy.' |
en |
dc.type |
Journal Article |
en |
dc.identifier.doi |
10.2337/db08-0140 |
en |
pubs.issue |
8 |
en |
pubs.begin-page |
2158 |
en |
pubs.volume |
57 |
en |
dc.rights.holder |
Copyright: American Diabetes Association |
en |
dc.identifier.pmid |
18492789 |
en |
pubs.end-page |
2166 |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/RestrictedAccess |
en |
pubs.subtype |
Article |
en |
pubs.elements-id |
79778 |
en |
pubs.org-id |
Medical and Health Sciences |
en |
pubs.org-id |
Medical Sciences |
en |
pubs.org-id |
Physiology Division |
en |
pubs.org-id |
Science |
en |
pubs.org-id |
Biological Sciences |
en |
pubs.org-id |
Science Research |
en |
pubs.org-id |
Maurice Wilkins Centre (2010-2014) |
en |
pubs.record-created-at-source-date |
2010-09-01 |
en |
pubs.dimensions-id |
18492789 |
en |