Exercise training alleviates MCT1 and MCT4 reductions in heart and skeletal muscles of STZ-induced diabetic rats

Enoki, Taisuke; Yoshida, Yuko; Hatta, Hideo; Bonen, Arend

doi:10.1152/japplphysiol.01155.2002

Cited by 40 publications

(46 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In our earlier study (10), after 1 wk of STZ-induced diabetes, we found that inhibition of lactate oxidation was not accompanied by decreased expression of monocarboxylate transporter-1 (MCT-1) expression or lactate dehydrogenase isoform expression (10); however, after longer periods of STZ-induced diabetes, MCT-1 expression in heart was reduced by ϳ30% (17). It was also shown that MCT-1 expression is reduced in skeletal muscle from obese, nondiabetic Zucker rats (38).…”

Section: Discussionmentioning

confidence: 99%

Impact of altered substrate utilization on cardiac function in isolated hearts from Zucker diabetic fatty rats

Wang

Lloyd²,

Zeng³

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

Self Cite

107

109

View full text Add to dashboard Cite

The goal of this study was to determine whether changes in cardiac metabolism in Type 2 diabetes are associated with contractile dysfunction or impaired response to ischemia. Hearts from Zucker diabetic fatty (ZDF) and lean control rats were isolated and perfused with glucose, lactate, pyruvate, and palmitate. The rates of glucose, lactate, pyruvate, and palmitate oxidation rates and glycolysis were determined during baseline perfusion and low-flow ischemia (LFI; 0.3 ml/min for 30 min) and after LFI and reperfusion. Under all conditions, ATP synthesis from palmitate was increased and synthesis from lactate was decreased in the ZDF group, whereas the contribution from glucose was unchanged. During baseline perfusion, the rate of glycolysis was lower in the ZDF group; however, during LFI and reperfusion, there were no differences between groups. Despite these metabolic shifts, there were no differences in oxygen consumption or ATP production rates between the groups under any perfusion conditions. Cardiac function was slightly depressed before LFI in the ZDF group, but during reperfusion, function was improved relative to the control group despite the increased dependence on fatty acids for energy production. These data suggest that in this model of diabetes, the shift from carbohydrates to fatty acids for oxidative energy production did not increase myocardial oxygen consumption and was not associated with impaired response to ischemia and reperfusion. contractile dysfunction; ischemia; nuclear magnetic resonance spectroscopy; carbohydrate metabolism DIABETES IS LINKED TO OBESITY, dyslipidemia, and hypertension (16,34,40,41), all of which are independent risk factors for cardiovascular disease (33,34,43); however, there is growing evidence to support the existence of a specific diabetic cardiomyopathy that is independent of other risk factors for heart disease (8 -11, 14, 21, 39, 42-44, 47, 48, 51). One of the earliest changes that occurs after the onset of experimentally induced diabetes is in the regulation of cardiac metabolism, typically characterized by increased fatty acid oxidation and decreased carbohydrate use (9). It has been suggested (26) that this shift in metabolism may play a role in the development of diabetic cardiomyopathy, which leads to both impaired contractile function as well as increased susceptibility to ischemic injury. For example, Belke et al. (2) found that increasing GLUT4 expression in hearts from diabetic db/db mice not only reversed the metabolic defects but also normalized cardiac function. However, treatment with a peroxisome proliferatoractivated receptor-␥ agonist in the same animal model of diabetes normalized the changes in cardiac metabolism, but contractile function remained depressed (5). Thus the potential role of altered substrate utilization in the development of cardiac dysfunction in diabetes remains to be determined.The increase in cardiac fatty acid utilization that occurs with diabetes is proposed to be detrimental because fatty acids are less-efficient fuels that...

show abstract

Section: Discussionmentioning

confidence: 99%

Impact of altered substrate utilization on cardiac function in isolated hearts from Zucker diabetic fatty rats

Wang

Lloyd²,

Zeng³

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

Self Cite

107

109

View full text Add to dashboard Cite

show abstract

“…For the analysis of MCT, proteins were isolated from muscles as our laboratory has described previously (4,5,16,36,47,48). MCTs were detected with Western blotting.…”

Section: Mct Proteinsmentioning

confidence: 99%

“…It is now confirmed that there is a family of eight or more MCTs (21). MCT isoforms are expressed in a tissue-specific manner (2, 5, 15-18, 20, 26, 28, 36, 38 -40, 42, 47, 49), and MCTs are also coexpressed within the same tissue (2,4,5,16,29,42,47,49). These latter observations suggest that MCTs may have different roles and/or transport capacities.…”

mentioning

confidence: 99%

“…Glycolytic muscle fibers express considerable quantities of MCT4, whereas MCT1 is predominantly present in oxidative muscle fibers in both slow-and fast-twitch muscles (2,5,12,16,36,42,47). It has been suggested that this MCT distribution among different types of muscle fibers may indicate that MCT1 is primarily involved with taking lactate up into the myocyte, whereas MCT4 may be primarily involved with extruding lactate (2,5,33).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Relationship between skeletal muscle MCT1 and accumulated exercise during voluntary wheel running

Yoshida

Hatta²,

Kato³

et al. 2004

Journal of Applied Physiology

Self Cite

View full text Add to dashboard Cite

. Relationship between skeletal muscle MCT1 and accumulated exercise during voluntary wheel running. J Appl Physiol 97: 527-534, 2004. First published April 23, 2004 10.1152/japplphysiol.01347.2003.-We examined whether the quantity of exercise performed influences the expression of monocarboxylate transporter (MCT) 1 and MCT4 in mouse skeletal muscles (plantaris, tibialis anterior, soleus) and heart. Wheel running exercise (1, 3, and 6 wk) was used, which results in marked variations in self-selected running activity. Differences in muscle MCT1 and MCT4 among animals, before the initiation of running, were not related to the quantity of exercise performed on the first day of wheel running. No changes in MCT4 were observed over the course of the study (P Ͼ 0.05). After 6 wk of running, were there significant increases in heart (50%; P Ͻ 0.05) and muscle MCT1 (31-60%; P Ͻ 0.05) but not after 1 and 3 wk (P Ͼ 0.05). Because skeletal muscle MCT1 and running distances varied considerably, we examined the relationship between these two parameters. Within the first week of training, MCT1 was negatively correlated with the accumulated running distance (r ϭ Ϫ0.70, P Ͻ 0.05). On further analysis, it appears that, in the first week, excessive running (Ͼ20 km/wk) represses MCT1 (Ϫ16.1%; P Ͻ 0.05), whereas more modest amounts of running (Ͻ20 km/wk) increase MCT1 (ϩ37%; P Ͻ 0.05). After 3 wk of running, a positive relationship was observed between MCT1 and running distance (r ϭ ϩ0.76), although there is a threshold that must be exceeded before an increase over the control animals occurs. Finally, in week 6, when MCT1 was increased in the tibialis anterior and plantaris muscles, there were no correlations with the accumulated running distances. These studies have shown that mild exercise training fails to increase MCT4 and that changes in MCT1 are complex, depending not only the accumulated exercise but also on the stage of training. lactate; plantaris; soleus; tibialis anterior; heart; distance; monocarboxylate transporter LACTATE IS NOT ONLY AN END product of glycolysis but also an oxidizable substrate. This monocarboxylate is produced primarily in fast-twitch skeletal muscle fibers, and it is oxidized in the heart and in oxidative muscle fibers. The productionoxidation cycle of lactate requires exchange of this substrate between muscle fibers and other muscles (2, 5, 49), as well as other tissues, including heart (4, 27, 28), liver (8), kidney (18,26,44), and adipose tissue (20), where lactate can be metabolized. The extrusion of lactate from the muscle cell and its uptake by other muscle cells occur via a facilitated transport system involving monocarboxylate transport (MCT) proteins. It is now confirmed that there is a family of eight or more MCTs (21). MCT isoforms are expressed in a tissue-specific manner (2, 5, 15-18, 20, 26, 28, 36, 38 -40, 42, 47, 49), and MCTs are also coexpressed within the same tissue (2,4,5,16,29,42,47,49). These latter observations suggest that MCTs may have different roles and/or transport capa...

show abstract

“…When glucose disposal is stimulated with insulin, plasma lactate concentration increases and the concentration is positively correlated with the rate of glucose disposal [16]. In STZ induced diabetes (which is a model of type 1 diabetes) resting blood lactate is reported to be elevated [17,18], and STZ induced diabetes in rats has also been found to decrease skeletal muscle lactate transport [17]. Studies have shown that mono-carboxylate transporters (MCT) dependent lactate-H + flux is facilitated by bicarbonate transporters and carbonic anhydrase enzyme in various cells and tissue [19,20].…”

Section: Introductionmentioning

confidence: 99%

Carbonic Anhydrase: A New Therapeutic Target for Managing Diabetes

Ismail¹,

Amodu²

2016

J Metabolic Synd

View full text Add to dashboard Cite

show abstract

Exercise training alleviates MCT1 and MCT4 reductions in heart and skeletal muscles of STZ-induced diabetic rats

Cited by 40 publications

References 39 publications

Impact of altered substrate utilization on cardiac function in isolated hearts from Zucker diabetic fatty rats

Impact of altered substrate utilization on cardiac function in isolated hearts from Zucker diabetic fatty rats

Relationship between skeletal muscle MCT1 and accumulated exercise during voluntary wheel running

Carbonic Anhydrase: A New Therapeutic Target for Managing Diabetes

Contact Info

Product

Resources

About