|
|
||||||||
-hydroxybutyrate impairs insulin
action in primary cultures of adult cardiomyocytes
1 Department of Medicine, Research Center, Centre Hospitalier de l'Université de Montréal, University of Montreal, Montreal H2W 1T8; and 2 Department of Medicine, Clinical Research Institute of Montreal, University of Montreal, Montreal, Canada H2W 1R7
Type 1 and type 2 diabetic patients often show elevated plasma ketone body
concentrations. Because ketone bodies compete with other energetic
substrates and reduce their utilization, they could participate in the
development of insulin resistance in the heart. We have examined the
effect of elevated levels of ketone bodies on insulin action in primary
cultures of adult cardiomyocytes. Cardiomyocytes were cultured with the
ketone body
-hydroxybutyrate (
-OHB) for 4 or 16 h, and
insulin-stimulated glucose uptake was evaluated. Although short-term
exposure to ketone bodies was not associated with any change in insulin
action, our data demonstrated that preincubation with
-OHB for
16 h markedly reduced insulin-stimulated glucose uptake in
cardiomyocytes. This effect is concentration dependent and persists for
at least 6 h after the removal of
-OHB from the media. Ketone
bodies also decreased the stimulatory effect of phorbol 12-myristate
13-acetate and pervanadate on glucose uptake. This diminution could not
be explained by a change in either GLUT-1 or GLUT-4 protein content in
cardiomyocytes. Chronic exposure to
-OHB was associated with
impaired protein kinase B activation in response to insulin and
pervanadate. These results indicate that prolonged exposure to ketone
bodies altered insulin action in cardiomyocytes and suggest that this
substrate could play a role in the development of insulin resistance in
the heart.
insulin resistance; ketone bodies; glucose uptake; protein kinase B; heart
This article has been cited by other articles:
![]() |
R. C. Waterman, E. E. Grings, T. W. Geary, A. J. Roberts, L. J. Alexander, and M. D. MacNeil Influence of seasonal forage quality on glucose kinetics of young beef cows J Anim Sci, October 1, 2007; 85(10): 2582 - 2595. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Pelletier and L. Coderre Ketone bodies alter dinitrophenol-induced glucose uptake through AMPK inhibition and oxidative stress generation in adult cardiomyocytes Am J Physiol Endocrinol Metab, May 1, 2007; 292(5): E1325 - E1332. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. C. Waterman, J. E. Sawyer, C. P. Mathis, D. E. Hawkins, G. B. Donart, and M. K. Petersen Effects of supplements that contain increasing amounts of metabolizable protein with or without Ca-propionate salt on postpartum interval and nutrient partitioning in young beef cows J Anim Sci, February 1, 2006; 84(2): 433 - 446. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Tardif, N. Julien, J.-L. Chiasson, and L. Coderre Stimulation of glucose uptake by chronic vanadate pretreatment in cardiomyocytes requires PI 3-kinase and p38 MAPK activation Am J Physiol Endocrinol Metab, June 1, 2003; 284(6): E1055 - E1064. [Abstract] [Full Text] [PDF] |
||||
![]() |
Z. Zou, S. Sasaguri, K. G. Rajesh, and R. Suzuki dl-3-Hydroxybutyrate administration prevents myocardial damage after coronary occlusion in rat hearts Am J Physiol Heart Circ Physiol, November 1, 2002; 283(5): H1968 - H1974. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |