'Altered calcium homeostasis fails to explain the contractile deficit of diabetic cardiomyopthy.'

Show simple item record

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. en
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

Files in this item

There are no files associated with this item.

Find Full text

This item appears in the following Collection(s)

Show simple item record


Search ResearchSpace