You are not logged in.

In vivo cardiac glucose metabolism in the high-fat fed mouse: comparison of euglycemic-hyperinsulinemic clamp derived measures of glucose uptake with a dynamic metabolomic flux profiling approach

Kowalski, Greg M., De Souza, David P., Risis, Steve, Burch, Micah L., Hamley, Steven, Kloehn, Joachim, Selathurai, Ahrathy, Lee-Young, Robert S., Tull, Dedreia, O'Callaghan, Sean, McConville, Malcolm J. and Bruce, Clinton R 2015, In vivo cardiac glucose metabolism in the high-fat fed mouse: comparison of euglycemic-hyperinsulinemic clamp derived measures of glucose uptake with a dynamic metabolomic flux profiling approach, Biochemical and biophysical research communications, vol. 463, no. 4, pp. 818-824, doi: 10.1016/j.bbrc.2015.06.019.

Attached Files
Name Description MIMEType Size Downloads

Title In vivo cardiac glucose metabolism in the high-fat fed mouse: comparison of euglycemic-hyperinsulinemic clamp derived measures of glucose uptake with a dynamic metabolomic flux profiling approach
Author(s) Kowalski, Greg M.ORCID iD for Kowalski, Greg M. orcid.org/0000-0002-1599-017X
De Souza, David P.
Risis, Steve
Burch, Micah L.
Hamley, Steven
Kloehn, Joachim
Selathurai, AhrathyORCID iD for Selathurai, Ahrathy orcid.org/0000-0003-2349-3496
Lee-Young, Robert S.
Tull, Dedreia
O'Callaghan, Sean
McConville, Malcolm J.
Bruce, Clinton RORCID iD for Bruce, Clinton R orcid.org/0000-0002-0515-3343
Journal name Biochemical and biophysical research communications
Volume number 463
Issue number 4
Start page 818
End page 824
Total pages 7
Publisher Elsevier
Place of publication Amsterdam, The Netherlands
Publication date 2015-07-13
ISSN 0006-291X
1090-2104
Keyword(s) Cardiac insulin resistance
Gas-chromatography mass spectrometry
Metabolomics
Stable isotopes
Summary Rationale Cardiac metabolism is thought to be altered in insulin resistance and type 2 diabetes (T2D). Our understanding of the regulation of cardiac substrate metabolism and insulin sensitivity has largely been derived from ex vivo preparations which are not subject to the same metabolic regulation as in the intact heart in vivo. Studies are therefore required to examine in vivo cardiac glucose metabolism under physiologically relevant conditions. Objective To determine the temporal pattern of the development of cardiac insulin resistance and to compare with dynamic approaches to interrogate cardiac glucose and intermediary metabolism in vivo. Methods and results Studies were conducted to determine the evolution of cardiac insulin resistance in C57Bl/6 mice fed a high-fat diet (HFD) for between 1 and 16 weeks. Dynamic in vivo cardiac glucose metabolism was determined following oral administration of [U-13C] glucose. Hearts were collected after 15 and 60 min and flux profiling was determined by measuring 13C mass isotopomers in glycolytic and tricarboxylic acid (TCA) cycle intermediates. Cardiac insulin resistance, determined by euglycemic-hyperinsulinemic clamp, was evident after 3 weeks of HFD. Despite the presence of insulin resistance, in vivo cardiac glucose metabolism following oral glucose administration was not compromised in HFD mice. This contrasts our recent findings in skeletal muscle, where TCA cycle activity was reduced in mice fed a HFD. Similar to our report in muscle, glucose derived pyruvate entry into the TCA cycle in the heart was almost exclusively via pyruvate dehydrogenase, with pyruvate carboxylase mediated anaplerosis being negligible after oral glucose administration. Conclusions Under experimental conditions which closely mimic the postprandial state, the insulin resistant mouse heart retains the ability to stimulate glucose metabolism.
Language eng
DOI 10.1016/j.bbrc.2015.06.019
Field of Research 090899 Food Sciences not elsewhere classified
111603 Systems Physiology
Socio Economic Objective 929999 Health not elsewhere classified
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2015, Elsevier
Persistent URL http://hdl.handle.net/10536/DRO/DU:30075918

Document type: Journal Article
Collection: School of Exercise and Nutrition Sciences
Connect to link resolver
 
Unless expressly stated otherwise, the copyright for items in DRO is owned by the author, with all rights reserved.

Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 0 times in TR Web of Science
Scopus Citation Count Cited 8 times in Scopus
Google Scholar Search Google Scholar
Access Statistics: 125 Abstract Views, 3 File Downloads  -  Detailed Statistics
Created: Thu, 17 Sep 2015, 12:33:31 EST

Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.