Những thay đổi do tập thể dục gây ra đối với MCT1 trong cơ tim và cơ vân của chuột đái tháo đường do chế độ ăn nhiều chất béo và STZ

Journal of Physiology and Biochemistry - Tập 69 - Trang 865-877 - 2013
Rohollah Nikooie1, Hamid Rajabi2, Reza Gharakhanlu3, Fereshteh Atabi4, Kobra Omidfar5, Malihe Aveseh1, Bagher Larijani6
1Department of Exercise Physiology, Faculty of Physical Education and Sport Science, Shahid Bahonar University of Kerman, Kerman, Iran
2Department of Exercise Physiology, Faculty of Physical Education and Sport Science, Kharazmi University, Tehran, Iran
3Department of Exercise Physiology, Faculty of Physical Education and Sport Science, Tarbiat Modares University, Tehran, Iran
4Endocrinology and Metabolism Research Center, Tehran University of Medical Sciences, Tehran, Iran
5Biosensor Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
6Endocrinology and Metabolism Research Institute, Tehran University of Medical Sciences, Tehran, Iran

Tóm tắt

Chúng tôi giả thuyết rằng một phần tác dụng điều trị của việc tập luyện endurance đối với kháng insulin được trung gian bởi sự gia tăng của chất vận chuyển lactate ty thể trong cơ tim và cơ vân, cụ thể là monocarboxylate transporter 1 (MCT1). Do đó, chúng tôi đã kiểm tra tác động của 7 tuần tập luyện endurance lên sự biểu hiện mRNA và protein của MCT1 và MCT4 cùng với chaperone của chúng, CD147, trên cả màng sarcolemmal và màng ty thể, một cách riêng biệt, ở chuột khỏe mạnh và chuột đái tháo đường type 2. Đái tháo đường được kích thích bằng cách tiêm một liều nhỏ streptozotocin và cho ăn chế độ ăn giàu chất béo. Kháng insulin đã được xác nhận thông qua chỉ số kháng insulin ước lượng theo mô hình cân bằng nội môi và độ chính xác của việc tách hai màng đã được xác nhận qua các dấu hiệu kiểm soát tiêu cực (glucose transporter 1 và cytochrome c oxidase). Real-time PCR và western blotting được sử dụng để phân tích sự biểu hiện mRNA và protein tương ứng. Đái tháo đường đã làm giảm đáng kể mRNA của MCT1 và MCT4 cũng như sự biểu hiện của chúng trên màng sarcolemmal, trong khi sự giảm biểu hiện của MCT1 trên màng ty thể ít hơn. Tập luyện đã làm gia tăng sự biểu hiện mRNA và protein của MCT1 trên cả hai màng và làm giảm kháng insulin như một hậu quả thích nghi. Trong cả hai mô, sự gia tăng mRNA CD147 chỉ tương đồng với sự biểu hiện của MCT1. Phản ứng của MCT1 trên màng sarcolemmal và màng ty thể là khác nhau giữa cơ tim và cơ vân, điều này cho thấy động lực học lactate trong tế bào mang tính mô học, cho phép mỗi mô điều chỉnh sự trao đổi chất toàn cơ thể.

Từ khóa

#MCT1 #MCT4 #CD147 #kháng insulin #tập luyện thể dục #chuột đái tháo đường

Tài liệu tham khảo

Andrew PH, Nigel TP (1999) The proton-linked monocarboxylate transporter (MCT) family: structure, function and regulation. Biochem J 343:281–299 Becker-immermann K, Berger M, Berchtold P, Gries FA, Herberg L, Schewenen M (1982) Treadmill training improves intravenous glucose tolerance and insulin sensitivity in fatty Zuckerrats. Diabetologia 22:468–474 Benton CR, Yoshida Y, Lally J, Han XX, Hatta H, Bonen A (2008) PGC-1α increases skeletal muscle lactate uptake by increasing the expression of MCT1 but not MCT2 or MCT4. Physiol Genomics 35:45–54 Bloomgarden MD (2005) Concepts of Insulin Resistance. Metab Syndr Relat Disord 3:284–293 Bonen A (2001) The expression of lactate transporters (MCT1 and MCT4) in heart and muscle. Eur J Appl Physiol 86:6–11 Bonen A, Mio T, Dragana M, Catherine H, John JH, Andrew P (2000) Isoform-specific regulation of the lactate transporters MCT1 and MCT4 by contractile activity. Am J Physiol Endocrinol Metab 279:E1131–E1138 Brooks GA (2009) Cell-cell and intracellular lactate shuttles. J Physiol 23:5591–5600 Brooks GA, Dubouchaud H, Brown M, Sicurello JP, Butz CE (1999) Role of mitochondrial lactate dehydrogenase and lactate oxidation in the intracellular lactate shuttle. J Physiol 96:1129–1134 Brooks GA, Brown MA, Butz CE, Sicurello JP, Dubouchaud H (1999) Cardiac and skeletal muscle mitochondria have a monocarboxylate transporter MCT1. J Appl Physiol 87(5):1713–1718 Butz CE, McClelland GB, Brooks GA (2004) MCT1 confirmed in rat striated muscle mitochondria. J Appl Physiol 97:1059–1066 Choi CS, Kim YB, LeeFN ZJM, Kahn BB, Youn JH (2002) Lactate induces insulin resistance in skeletal muscle by suppressing glycolysis and impairing insulin signaling. Am J Physiol Endocrinol Metab 283:E233–E240 Defronzo RA, Simonson D, Ferrannini E (1982) Hepatic and peripheral insulin resistance: a common feature of type 2 (non-insulin dependent) and type 1 (insulin dependent) diabetes mellitus. Diabetologia 23:313–319 Deora AA, Philp N, Hu J, Bok D, Rodriguez-Boulan E (2005) Mechanisms regulating tissue-specific polarity of monocarboxylate transporters and their chaperone CD147 in kidney and retinal epithelia. PNAS 45:16245–16250 DiGirolamo M, Newby FD, Lovejoy J (1992) Lactate production in adipose tissue: a regulated function with extraadipose implications. FASEB J 6:2405–2412 Dubouchaud H, Butterfield GE, Wolfel EE, Bergman BC, Brooks GA (2000) Endurance training, expression and physiology of LDH, MCT1 and MCT4 in skeletal muscle. Am J Physiol Endocrinol Metab 278:E571–E579 Dubouchaud H, Granier P, Mercier J, Le Peuch C, Prefaut C (1996) Lactate uptake by skeletal muscle sarcolemmal vesicles decreases after 4 wk of hindlimb unweighting in rats. J Appl Physiol 80:416–421 Enoki T, Yoshida Y, Hatta H, Bonen A (2003) Exercise training alleviates MCT1 and MCT4 reductions in heart and skeletal muscles of STZ induced diabetic rats. J Appl Physiol 94:2433–2438 Enoki T, Yoshida Y, Lally J, Hatta H, Bonen A (2006) Testosterone increases lactate transport, monocarboxylate transporter MCT1 and MCT4 in rat skeletal muscle. J Physiol 1:433–443 Frøsig C, Rose AJ, Treebak JT, Kiens B, Richter EA, Wojtaszewski JF (2007) Effects of endurance exercise training on insulin signaling in human skeletal muscle: interactions at the level of PI3-K, Akt and AS160. Diabetes 56:2093–2102 Goodyear LJ, Hirshman MF, Knutson SM, Horton ED, Horton ES (1974) Effect of exercise training on glucose homeostasis in normal and insulin-deficient diabetic rats. J Appl Physiol 65:844–851 Gutmann L, Wahlefeld AW (1974) l-lactate determination with lactate dehydrogenase and NAD. Meth Enzym Anal 1464–1472 Hashimoto T, Hussien R, Cho HS, Kaufer D, Brooks GA (2008) Evidence for the mitochondrial lactate oxidation complex in rat neurons: demonstration of an essential component of brain lactate shuttles. PLoS One 3(8):e2915 Kelley KM, Hamann JJ, Navarre C, Gladden LB (2002) Lactate metabolism in resting and contracting canine skeletal muscle with elevated lactate concentration. J Appl Physiol 93:865–872 Kirk P, Wilson MC, Heddle C, Brown MH, Barclay AN, Halestrap AP (2000) CD147 is tightly associated with lactate transporters MCT1 and MCT4 and facilitates their cell surface expression. EMBO J 19(15):3896–904 Kraniou GN, Cameron-Smith D, Hargreaves M (2006) Acute exercise and GLUT4 expression in human skeletal muscle: influence of exercise intensity. J Appl Physiol 101:934–937 Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2−Delta Delta C(T). Method 25:402–408 Liu H, Colavitti R, Rovira II, Finkel T (2005) Redox-dependent transcriptional regulation. Circ Res 97:967–974 Lombardi AM, Fabris R, Bassetto F, SerrR LA, Federspil G, Girard J, Vettor R (1999) Hyperlactatemia reduces muscle glucose uptake and GLUT-4 mRNA while increasing (E1a)PDH gene expression in rat. Am J Physiol Endocrinol Metab 39:E922–E929 Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419 McCullagh KJ, Bonen A (1995) Reduced lactate transport in denervated rat skeletal muscle. Am J Physiol Regul Integr Comp Physiol 268:R884–R888 Metz L, Sirvent P, Py G, Brun JF, Fédou C, Raynaud E, Mercier J (2005) Relationship between blood lactate concentration and substrate utilization during exercise in type 2 diabetic postmenopausal women metabolism. Clin Exp 54:1102–1107 Miyamoto S, Chiorini JA, Urcelay E, Safer B (1996) Regulation of gene expression for translation initiation factor eIF-2 alpha: importance of the 3′ untranslatedregion. Biochem J 315:791–798 Mondon CE, Jones IR, Azhar S, Hollenbeck CB, Reaven GM (1992) Lactate production and pyruvate dehydrogenase activity in fat and skeletal muscle from diabetic rats. Diabetes 41:1547–1554 O’Gorman DJ, Karlsson HK, McQuaid S, Yousif O, Rahman Y, Gasparro D, Glund S, Chibalin AV, Zierath JR, Nolan JJ (2006) Exercise training increases insulin-stimulated glucose disposal and GLUT4 (SLC2A4) protein content in patients with type 2 diabetes. Diabetologia 49:2983–2992 Pérez de Heredia F, Wood IS, Trayhurn P (2010) Hypoxia stimulates lactate release and modulates monocarboxylate transporter (MCT1, MCT2, and MCT4) expression in human adipocytes. Pflugers Arch-Eur J Physiol 459:509–518 Philp NJ, Ochrietor JD, Rudoy C, Muramatsu T, Linser PJ (2003) Loss of MCT1, MCT3, and MCT4 expression in the retinal pigment epithelium and neural retina of the 5A11/basigin-null mouse. Invest Ophthalmol Vis Sci 44:1305–1311 Randle PJ, Garland PB, Hales CN, Newsholme EA (1963) The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet 1:785–789 Reed MJ, Meszaros K, Entes LJ, Claypool MD, Pinkett JG, Gadbois TM, Reaven GM (2000) A new rat model of type 2 diabetes: the fat-fed, streptozotocin-treated rat. Metabolism 49:1390–1394 Russell AP, Feilchenfeldt J, Schreiber S, Praz M, Crettenand A, Gobelet C, Meier CA, Bell DR, Kralli A, Giacobino JP, Deriaz O (2003) Endurance training in humans leads to fiber type-specific increases in levels of peroxisome proliferator-activated receptor-gamma coactivator-1 and peroxisome proliferator-activated receptor-alpha in skeletal muscle. Diabetes 52:2874–2881 Schneiderhan W, Scheler M, Holzmann KH, Marx M, Gschwend JE, Bucholz M, Gress TM, Seufferlein T, Adler G, Oswald F (2009) CD147 silencing inhibits lactate transport and reduces malignant potential of pancreatic cancer cells in in vivo and in vitro models. Gut 58:1391–1398 Schwoch C, Pasoow H (1984) preparation and properties of human erythrocyte ghosts. Mol Cell Biochem 152(2):197–218 Sharma AK, Srinivasan BP (2009) Triple verses glimepiride plus metformin therapy on cardiovascular risk biomarkers and diabetic cardiomyopathy in insulin resistance type 2 diabetes mellitus rats. Eur J Pharm Sci 38:433–444 Srinivasan K, Viswanad B, Asrat L, Kaul CL, Ramarao P (2005) Combination of high-fat diet-fed and low-dose streptozotocin-treated rat: a model for type 2 diabetes and pharmacological screening Srinivasan. Pharmacol Res 52:313–320 Terada S, Tabata I (2004) Effects of acute bouts of running and swimming exercise on PGC-1alpha protein expression in rat epitrochlearis and soleus muscle. Am J Physiol Endocrinol Metab 286:E208–E216 Ullah MS, Davies AJ, Halestrap AP (2006) The plasma membrane lactate transporter MCT4, but not MCT1, is up-regulated by hypoxia through a HIF-1-dependent mechanism. J Biol Chem 281:9030–9037 Valenti D, de Bari L, Atlante A, Passarella S (2002) l-lactate transport into rat heart mitochondria and reconstruction of the l-lactate/pyruvate shuttle. Biochem J 364:101–104 Vettor R, Lombardi AM, Fabris R, Pagano C, Cusin I, Rohner JF, Federspil G, Jeanrenaud B (1997) Lactate Infusion in anesthetized rats produces insulin resistance in heart and skeletal muscles. Metabolism 46:684–690 Wincey C, Marks V (1961) A micro-method for measuring glucose using the autoanalyzer and glucose-oxidase. J Clin Pathol 14:558–559 Wright DC, Geiger PC, Han DH, Jones TE, Holloszy JO (2007) Calcium induces increases in peroxisome proliferator-activated receptor gamma coactivator-1alpha and mitochondrial biogenesis by a pathway leading to p38 mitogen activated protein kinase activation. J Biol Chem 82:18793–18799 Zhang F, Ye C, Li G, Ding W, Zhou W, Zhu H, Chen G, Luo T, Guang M, Liu Y, Zhang D, Zheng S, Yang J, Gu Y, Xie X, Luo M (2003) The rat model of type 2 diabetic mellitus and its glycometabolism character. Exp Anim 52(5):401–407