Exercise-induced changes of MCT1 in cardiac and skeletal muscles of diabetic rats induced by high-fat diet and STZ

Nikooie, Rohollah; Rajabi, Hamid; Reza, Gharakhanlu; Atabi, Fereshteh; Omidfar, Kobra; Aveseh, Malihe; Larijani, Bagher

doi:10.1007/s13105-013-0263-6

Cited by 28 publications

(20 citation statements)

References 47 publications

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“…Only this high dose of STZ induced weight loss, and produced a plasma metabolite profile that included hyperketonaemia, hyperlipidaemia, and hypoinsulinaemia. This is in agreement with other studies that have used high doses of STZ in isolation or in combination with high-fat feeding [19,36-39], with these high doses also causing abnormalities in liver morphology and function [25]. In contrast, the lower doses of STZ investigated in the present study avoided these extreme phenotypes, instead presenting with hyperglycaemia in the absence of ketosis, normoinsulinaemia and with maintenance of body weight.…”

Section: Discussionsupporting

confidence: 93%

Cardiac metabolism in a new rat model of type 2 diabetes using high-fat diet with low dose streptozotocin

Mansor

Gonzalez

Cole

et al. 2013

Cardiovasc Diabetol

121

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BackgroundTo study the pathogenesis of diabetic cardiomyopathy, reliable animal models of type 2 diabetes are required. Physiologically relevant rodent models are needed, which not only replicate the human pathology but also mimic the disease process. Here we characterised cardiac metabolic abnormalities, and investigated the optimal experimental approach for inducing disease, in a new model of type 2 diabetes.Methods and resultsMale Wistar rats were fed a high-fat diet for three weeks, with a single intraperitoneal injection of low dose streptozotocin (STZ) after fourteen days at 15, 20, 25 or 30 mg/kg body weight. Compared with chow-fed or high-fat diet fed control rats, a high-fat diet in combination with doses of 15–25 mg/kg STZ did not change insulin concentrations and rats maintained body weight. In contrast, 30 mg/kg STZ induced hypoinsulinaemia, hyperketonaemia and weight loss. There was a dose-dependent increase in blood glucose and plasma lipids with increasing concentrations of STZ. Cardiac and hepatic triglycerides were increased by all doses of STZ, in contrast, cardiac glycogen concentrations increased in a dose-dependent manner with increasing STZ concentrations. Cardiac glucose transporter 4 protein levels were decreased, whereas fatty acid metabolism-regulated proteins, including uncoupling protein 3 and pyruvate dehydrogenase (PDH) kinase 4, were increased with increasing doses of STZ. Cardiac PDH activity displayed a dose-dependent relationship between enzyme activity and STZ concentration. Cardiac insulin-stimulated glycolytic rates were decreased by 17% in 15 mg/kg STZ high-fat fed diabetic rats compared with control rats, with no effect on cardiac contractile function.ConclusionsHigh-fat feeding in combination with a low dose of STZ induced cardiac metabolic changes that mirror the decrease in glucose metabolism and increase in fat metabolism in diabetic patients. While low doses of 15–25 mg/kg STZ induced a type 2 diabetic phenotype, higher doses more closely recapitulated type 1 diabetes, demonstrating that the severity of diabetes can be modified according to the requirements of the study.

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Section: Discussionsupporting

confidence: 93%

Cardiac metabolism in a new rat model of type 2 diabetes using high-fat diet with low dose streptozotocin

Mansor

Gonzalez

Cole

et al. 2013

Cardiovasc Diabetol

121

View full text Add to dashboard Cite

show abstract

“…Our results indicated that MCT4 expression and its location on plasma membrane were decreased under HG and IL-1b condition in HUVECs. Nikooie et al demonstrated that diabetes dramatically reduced MCT4 mRNA and their expression on sarcolemmal membrane [26]. Thus, the decrease of MCT4 may be involved in inflammation and metabolic changes (hyperglycemia).…”

Section: Discussionmentioning

confidence: 99%

High glucose and interleukin 1β-induced apoptosis in human umbilical vein endothelial cells involves in down-regulation of monocarboxylate transporter 4

Wang

Yan

et al. 2015

Biochemical and Biophysical Research Communications

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Hyperglycaemia and inflammatory can induce apoptosis in vascular endothelial cells, which contributes to the development of vascular complications in diabetes. Endothelial cells depend on glycolysis for their energy metabolism, and monocarboxylate transporters (MCTs) regulate intracellular pH by mediating the influx and efflux of lactate. Here, we evaluate the role of MCT4 in high glucose (HG) and interleukin 1β (IL-1β)-induced apoptosis in human umbilical vein endothelial cells (HUVECs). We demonstrate that aortic endothelium damage is severe in db/db mice by using scanning ion conductance microscopy (SICM). HG and IL-1β decrease MCT4 and its location on plasma membrane, as well as increase lactic acid accumulation and apoptosis in HUVECs. Knockdown of MCT4 blocks lactate efflux to result in lactic acid accumulation and pH dropping, which is involved in triggering apoptosis in HUVECs.

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“…2000 ng of total RNA was added to each 40 μl cDNA synthesis reaction, which was reverse transcribed to cDNA using iScript Reverse Transcription Supermix (BioRad). Primer sequences, annealing temperatures and product sizes for quantitative real-time PCR are shown in Table 1 (14,15). Primers were validated by running endpoint PCR with 250 nM forward and reverse primers, 1 μl of cDNA and iTaq Universal SYBR Green Supermix (BioRad) following the manufacturer's instructions.…”

Section: Animals Estrus Staging and Tissue Collectionmentioning

confidence: 99%

Sex Hormones Regulate Rat Hepatic Monocarboxylate Transporter Expression and Membrane Trafficking

Cao

Felmlee

2017

J Pharm Pharm Sci

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-Purpose: Monocarboxylate transporters (MCTs) are involved in the transport of monocarboxylates such as ketone bodies, lactate, and pharmaceutical agents. CD147 functions as an ancillary protein for MCT1 and MCT4 for plasma membrane trafficking. Sex differences in MCT1 and MCT4 have been observed in muscle and reproductive tissues; however, there is a paucity of information on MCT sex differences in tissues involved in drug disposition. The objective of the present study was to quantify hepatic MCT1, MCT4 and CD147 mRNA, total cellular and membrane protein expression in males, over the estrous cycle in females and in ovariectomized (OVX) females. Method: Liver samples were collected from females at the four estrous cycle stages (proestrus, estrus, metestrus, diestrus), OVX females and male Sprague-Dawley rats (N = 3 -5). Estrus cycle stage of females was determined by vaginal lavage. mRNA and protein (total and membrane) expression of MCT1, MCT4 and CD147 was evaluated by qPCR and western blot analysis. Results: MCT1 mRNA and membrane protein expression varied with estrous cycle stage, with OVX females having higher expression than males, indicating that female sex hormones may play a role in MCT1 regulation. MCT4 membrane expression varied with estrous cycle stage with expression significantly lower than males. MCT4 membrane expression in OVX females was also lower than males, suggesting that androgens play a role in membrane expression of MCT4. Males had higher membrane CD147 expression, whereas there was no difference in whole cell protein and mRNA levels suggesting that androgens are involved in regulating CD147 membrane localization. Conclusions: This study demonstrates hepatic expression and membrane localization of MCT1, MCT4 and CD147 are regulated by sex hormones. Sex differences in hepatic MCT expression may lead to altered drug disposition, so it is critical to elucidate the underlying mechanisms in the sex hormone-dependent regulation of MCT expression.

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Exercise-induced changes of MCT1 in cardiac and skeletal muscles of diabetic rats induced by high-fat diet and STZ

Cited by 28 publications

References 47 publications

Cardiac metabolism in a new rat model of type 2 diabetes using high-fat diet with low dose streptozotocin

Cardiac metabolism in a new rat model of type 2 diabetes using high-fat diet with low dose streptozotocin

High glucose and interleukin 1β-induced apoptosis in human umbilical vein endothelial cells involves in down-regulation of monocarboxylate transporter 4

Sex Hormones Regulate Rat Hepatic Monocarboxylate Transporter Expression and Membrane Trafficking

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