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Abstract
Insulin resistance is a prevalent disorder among horses and is associated with abnormal adiposity, laminitis, equine metabolic syndrome, and pituitary pars intermedia dysfunction. The processes leading to equine insulin resistance and associated conditions remain subject for study. MicroRNAs (miRNAs) are involved in regulation of many biological processes and diseases. The current study aimed to investigate the circulating miRNA profile of insulin resistant horses and ponies. It was hypothesized that insulin resistant horses would have a different circulating miRNA profile compared to healthy ones. 12 Thoroughbred/ Thoroughbred-cross and 12 Welsh/Dartmoor non-pregnant mares were evaluated for insulin sensitivity using frequent sampling intravenous glucose tolerance test (FSIGTT). Serum samples were collected for miRNA profiling through RT-qPCR analysis. Horses and ponies were divided into insulin sensitive (IS) or insulin resistant (IR) groups and their miRNA profiles compared. Results demonstrated that 13 miRNAs were differently expressed between IR and IS horses, 15 between IR and IS ponies, 17 between horses and ponies, and 10 between IR and IS animals (horses and ponies combined) (p<0.05). Finally, 8 miRNAs were proposed as potential regulators of equine insulin resistance. miRNA profiling is a potential tool to evaluate insulin resistance and associated conditions.
References
Ardekani, A. M., & Naeini, M. M. (2010). The Role of MicroRNAs in Human Diseases. Avicenna Journal of Medical Biotechnology, 2(4), 161-179. http://dx.doi.org/10.1007/978-1-62703-748-8_3. PMid:23407304.
Bailey, S. R., Habershon-Butcher, J. L., Ransom, K. J., Elliott, J., & Menzies-Gow, N. J. (2008). Hypertension and insulin resistance in a mixed-breed population of ponies predisposed to laminitis. American Journal of Veterinary Research, 69(1), 122-129. http://dx.doi.org/10.2460/ajvr.69.1.122. PMid:18167097.
Bailey, S. R., Rycroft, A., & Elliott, J. (2002). Production of amines in equine cecal contents in an in vitro model of carbohydrate overload. Journal of Animal Science, 80(10), 2656-2662. http://dx.doi.org/10.2527/2002.80102656x. PMid:12413088.
Bamford, N. J., Potter, S. J., Harris, P. A., & Bailey, S. R. (2014). Breed differences in insulin sensitivity and insulinemic responses to oral glucose in horses and ponies of moderate body condition score. Domestic Animal Endocrinology, 47, 101-107. http://dx.doi.org/10.1016/j.domaniend.2013.11.001. PMid:24308928.
Becker, N., & Lockwood, C.M. “Pre-analytical variables in miRNA analysis.” Clinical Biochemistry . 46,10-11 (2013): 861-8. doi:10.1016/j.clinbiochem.2013.02.015
Borer, K. E., Berhane, Y., Menzies-Gow, N. J., Harris, P. A., & Elliott, J. (2009) Measurement of concentrations of insulin in equine serum that exceed the working range of radioimmunoassay kits. In: Proceedings of the 48th British Equine Veterinary Association Congress, Equine Veterinary Journal Ltd, Fordham. p 103.
Calvier, L., Chouvarine, P., Legchenko, E., Hoffmann, N., Geldner, J., Borchert, P., Jonigk, D., Mozes, M. M., & Hansmann, G. (2017). PPARγ Links BMP2 and TGFβ1 Pathways in Vascular Smooth Muscle Cells, Regulating Cell Proliferation and Glucose Metabolism. Cell Metabolism, 25(5), 1118-1134.e7. http://dx.doi.org/10.1016/j. cmet.2017.03.011. PMid:28467929.
Chartoumpekis, D. V., Zaravinos, A., Ziros, P.G., Iskrenova, R.P., Psyrogiannis, A.I., Kyriazopoulou, V.E. & Habeos, I.G. (2012) Differential expression of microRNAs in adipose tissue after long-term high-fat diet-induced obesity in mice. PLoS One 7(4):e34872. http://dx.doi.org/10.1371/journal.pone.0034872.
Chen, G. Q., Lian, W. J., Wang, G. M., Wang, S., Yang, Y. Q., & Zhao, Z. W. (2012). Altered microRNA expression in skeletal muscle results from high-fat diet-induced insulin resistance in mice. Molecular Medicine Reports, 5(5), 1362-1368. http://dx.doi.org/10.3892/mmr.2012.824. PMid:22395471.
Collares, C. V., Evangelista, A. F., Xavier, D. J., Rassi, D. M., Arns, T., Foss-Freitas, M. C., Foss, M. C., Puthier, D., Sakamoto-Hojo, E. T., Passos, G. A., & Donadi, E. A. (2013). Identifying common and specific microRNAs expressed in peripheral blood mononuclear cell of type 1, type 2, and gestational diabetes mellitus patients. BMC Research Notes, 6(1), 491. http://dx.doi.org/10.1186/1756-0500-6-491. PMid:24279768.
Cui, X., You, L., Zhu, L., Wang, X., Zhou, Y., Li, Y., Wen, J., Xia, Y., Wang, X., Ji, C., & Guo, X. (2018). Change in circulating microRNA profile of obese children indicates future risk of adult diabetes. Metabolism: Clinical and Experimental, 78, 95-105. http://dx.doi.org/10.1016/j.metabol.2017.09.006. PMid:28966078.
da Costa Santos, H., Hess, T., Bruemmer, J., & Splan, R. (2018). Possible role of microRNA in equine insulin resistance: A pilot study. Journal of Equine Veterinary Science, 63, 74-79. http://dx.doi.org/10.1016/j.jevs.2017.10.024.
DeFronzo, R. A., Tobin, J. D., & Andres, R. (1979). Glucose clamp technique: A method for quantifying insulin secretion and resistance. The American Journal of Physiology, 237(3), E214-E223. http://dx.doi.org/10.1152/ ajpendo.1979.237.3.E214. PMid:382871.
Donaldson, M. T., McDonnell, S. M., Schanbacher, B. J., Lamb, S. V., McFarlane, D., & Beech, J. (2005). Variation in plasma adrenocorticotropic hormone concentration and dexamethasone suppression test results with season, age, and sex in healthy ponies and horses. Journal of Veterinary Internal Medicine, 19(2), 217-222. http://dx.doi.org/10.1111/j.1939-1676.2005.tb02685.x. PMid:15822567.
Dou, L., Zhao, T., Wang, L., Huang, X., Jiao, J., Gao, D., Zhang, H., Shen, T., Man, Y., Wang, S., & Li, J. (2013). miR- 200s contribute to interleukin-6 (IL-6)-induced insulin resistance in hepatocytes. The Journal of Biological Chemistry, 288(31), 22596-22606. http://dx.doi.org/10.1074/jbc.M112.423145. PMid:23798681.
Eder, K., Baffy, N., Falus, A., & Fulop, A. K. (2009). The major inflammatory mediator interleukin-6 and obesity. Inflammation Research: Official Journal of the European Histamine Research Society ... [et al.], 58(11), 727-736. https://doi.org/10.1007/s00011-009-0060-4.
Erener, S., Marwaha, A., Tan, R., Panagiotopoulos, C., & Kieffer, T. J. (2017). Profiling of circulating microRNAs in children with recent onset of type 1 diabetes. JCI Insight, 2(4), e89656. http://dx.doi.org/10.1172/jci.insight.89656. PMid:28239651.
Esau, C., Davis, S., Murray, S. F., Yu, X. X., Pandey, S. K., Pear, M., Watts, L., Booten, S. L., Graham, M., McKay, R., Subramaniam, A., Propp, S., Lollo, B. A., Freier, S., Bennett, C. F., Bhanot, S., & Monia, B. P. (2006). miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting. Cell Metabolism, 3(2), 87-98. http:// dx.doi.org/10.1016/j.cmet.2006.01.005. PMid:16459310.
Frank, N., Geor, R. J., Bailey, S. R., Durham, A. E., & Johnson, P. J., & American College of Veterinary Internal Medicine (2010). Equine metabolic syndrome. Journal of Veterinary Internal Medicine, 24(3), 467-475. http:// dx.doi.org/10.1111/j.1939-1676.2010.0503.x. PMid:20384947.
Freestone, J. F., Shoemaker, K., Bessin, R., & Wolfsheimer, J. K. (1992). Insulin and glucose response following oral glucose administration in well-conditioned ponies. Equine Veterinary Journal. Supplement, 24(11), 13-17. http://dx.doi.org/10.1111/j.2042-3306.1992.tb04764.x. PMid:9109953.
Frost, R. J., & Olson, E. N. (2011). Control of glucose homeostasis and insulin sensitivity by the Let-7 family of microRNAs. Proceedings of the National Academy of Sciences of the United States of America, 108(52), 21075- 21080. http://dx.doi.org/10.1073/pnas.1118922109. PMid:22160727.
Gallagher, I. J., Scheele, C., Keller, P., Nielsen, A. R., Remenyi, J., Fischer, C. P., Roder, K., Babraj, J., Wahlestedt, C., Hutvagner, G., Pedersen, B. K., & Timmons, J. A. (2010). Integration of microRNA changes in vivo identifies novel molecular features of muscle insulin resistance in type 2 diabetes. Genome Medicine, 2(2), 9. http:// dx.doi.org/10.1186/gm130. PMid:20353613.
Garner, H. E., Hutcheson, D. P., Coffman, J. R., Hahn, A. W., & Salem, C. (1977). Lactic acidosis: A factor associated with equine laminitis. Journal of Animal Science, 45(5), 1037-1041. http://dx.doi.org/10.2527/jas1977.4551037x. PMid:599094.
Geor, R. J. (2010). Current concepts on the pathophysiology of pasture-associated laminitis. The Veterinary Clinics of North America. Equine Practice, 26(2), 265-276. http://dx.doi.org/10.1016/j.cveq.2010.06.001. PMid:20699174.
Geor, R. J. (2013). Endocrine and metabolic physiology. In R. J. Geor, P. A. Harris & M. Coenen (Eds.), Equine Applied and Clinical Nutrition: Health, Welfare and Performance (pp. 33-63). Filadélfia: W. B. Saunders Company. http:// dx.doi.org/10.1016/B978-0-7020-3422-0.00002-X.
Herrera, B. M., Lockstone, H. E., Taylor, J. M., Ria, M., Barrett, A., Collins, S., Kaisaki, P., Argoud, K., Fernandez, C., Travers, M. E., Grew, J. P., Randall, J. C., Gloyn, A. L., Gauguier, D., McCarthy, M. I., & Lindgren, C. M. (2010). Global microRNA expression profiles in insulin target tissues in a spontaneous rat model of type 2 diabetes. Diabetologia, 53(6), 1099-1109. http://dx.doi.org/10.1007/s00125-010-1667-2. PMid:20198361.
Hoffman, R. M., Boston, R. C., Stefanovski, D., Kronfeld, D. S., & Harris, P. A. (2003). Obesity and diet affect glucose dynamics and insulin sensitivity in Thoroughbred geldings. Journal of Animal Science, 81(9), 2333-2342. http://dx.doi.org/10.2527/2003.8192333x. PMid:12968709.
Jeffcott, L. B., Field, J. R., McLean, J. G., & O’Dea, K. (1986). Glucose tolerance and insulin sensitivity in ponies and Standardbred horses. Equine Veterinary Journal, 18(2), 97-101. http://dx.doi.org/10.1111/j.2042-3306.1986. tb03556.x. PMid:3516677.
Jiang, L. Q., Franck, N., Egan, B., Sjögren, R. J., Katayama, M., Duque-Guimaraes, D., Arner, P., Zierath, J. R., & Krook, A. (2013). Autocrine role of interleukin-13 on skeletal muscle glucose metabolism in type 2 diabetic patients involves microRNA let-7. American Journal of Physiology. Endocrinology and Metabolism, 305(11), E1359-E1366. http://dx.doi.org/10.1152/ajpendo.00236.2013. PMid:24105413.
Kahn, B. B., & Flier, J. S. (2000). Obesity and insulin resistance. The Journal of Clinical Investigation, 106(4), 473- 481. http://dx.doi.org/10.1172/JCI10842. PMid:10953022.
Kameswaran, V., Bramswig, N. C., McKenna, L. B., Penn, M., Schug, J., Hand, N. J., Chen, Y., Choi, I., Vourekas, A., Won, K. J., Liu, C., Vivek, K., Naji, A., Friedman, J. R., & Kaestner, K. H. (2014). Epigenetic regulation of the DLK1-MEG3 microRNA cluster in human type 2 diabetic islets. Cell Metabolism, 19(1), 135-145. http://dx.doi. org/10.1016/j.cmet.2013.11.016. PMid:24374217.
Karagkouni, D., Paraskevopoulou, M. D., Chatzopoulos, S., Vlachos, I. S., Tastsoglou, S., Kanellos, I., Papadimitriou, D., Kavakiotis, I., Maniou, S., Skoufos, G., Vergoulis, T., Dalamagas, T., & Hatzigeorgiou, A. G. (2018). DIANA-TarBase v8: A decade-long collection of experimentally supported miRNA-gene interactions. Nucleic Acids Research, 46(D1), D239-D245. http://dx.doi.org/10.1093/nar/gkx1141. PMid:29156006.
Karolina, D. S., Armugam, A., Tavintharan, S., Wong, M. T., Lim, S. C., Sum, C. F., & Jeyaseelan, K. (2011). MicroRNA 144 impairs insulin signaling by inhibiting the expression of insulin receptor substrate 1 in type 2 diabetes mellitus. PLoS One, 6(8), e22839. http://dx.doi.org/10.1371/journal.pone.0022839. PMid:21829658.
Kato, M., Putta, S., Wang, M., Yuan, H., Lanting, L., Nair, I., Gunn, A., Nakagawa, Y., Shimano, H., Todorov, I., Rossi, J. J., & Natarajan, R. (2009). TGF-beta activates Akt kinase through a microRNA-dependent amplifying circuit targeting PTEN. Nature Cell Biology, 11(7), 881-889. http://dx.doi.org/10.1038/ncb1897. PMid:19543271.
Klöting, N., Berthold, S., Kovacs, P., Schön, M. R., Fasshauer, M., Ruschke, K., Stumvoll, M., & Blüher, M. (2009). MicroRNA expression in human omental and subcutaneous adipose tissue. PLoS One, 4(3), e4699. http:// dx.doi.org/10.1371/journal.pone.0004699. PMid:19259271.
Kronfeld, D., & Harris, P. (2003). Equine grain-associated disorders. The Compendium on Continuing Education for the Practicing Veterinarian, 25, 974-983.
Lecchi, C., Dalla Costa, E., Lebelt, D., Ferrante, V., Canali, E., Ceciliani, F., Stucke, D., & Minero, M. (2018). Circulating miR-23b-3p, miR-145-5p and miR-200b-3p are potential biomarkers to monitor acute pain associated with laminitis in horses. Animal: an International Journal of Animal Bioscience, 12(2), 366-375. https://doi.org/10.1017/ S1751731117001525.
Lewis, S. L., Holl, H. M., Streeter, C., Posbergh, C., Schanbacher, B. J., Place, N. J., Mallicote, M. F., Long, M. T., & Brooks, S. A. (2017). Genomewide association study reveals a risk locus for equine metabolic syndrome in the Arabian horse. Journal of Animal Science, 95(3), 1071-1079. http://dx.doi.org/10.2527/jas2016.1221. PMid:28380523.
Li, A., Qiu, M., Zhou, H., Wang, T., & Guo, W. (2017). PTEN, insulin resistance and cancer. Current Pharmaceutical Design, 23(25), 3667-3676. http://dx.doi.org/10.2174/1381612823666170704124611. PMid:28677502.
Li, Z. Y., Na, H. M., Peng, G., Pu, J., & Liu, P. (2011). Alteration of microRNA expression correlates to fatty acid-mediated insulin resistance in mouse myoblasts. Molecular BioSystems, 7(3), 871-877. http://dx.doi.org/10.1039/ C0MB00230E. PMid:21183973.
Lindåse, S., Müller, C., Nostell, K., & Bröjer, J. (2018). Evaluation of glucose and insulin response to haylage diets with different content of nonstructural carbohydrates in 2 breeds of horses. Domestic Animal Endocrinology, 64, 49-58. http://dx.doi.org/10.1016/j.domaniend.2018.03.006. PMid:29751248.
Liu, W., Bi, P., Shan, T., Yang, X., Yin, H., Wang, Y. X., Liu, N., Rudnicki, M. A., & Kuang, S. (2013). miR-133a regulates adipocyte browning in vivo. PLOS Genetics, 9(7), e1003626. http://dx.doi.org/10.1371/journal.pgen.1003626. PMid:23874225.
Locke, J. M., da Silva Xavier, G., Dawe, H. R., Rutter, G. A., & Harries, L. W. (2014). Increased expression of miR- 187 in human islets from individuals with type 2 diabetes is associated with reduced glucose-stimulated insulin secretion. Diabetologia, 57(1), 122-128. http://dx.doi.org/10.1007/s00125-013-3089-4. PMid:24149837.
Longland, A. C., & Byrd, B. M. (2006). Pasture nonstructural carbohydrates and equine laminitis. The Journal of Nutrition, 136(7, Suppl), 2099S-2102S. http://dx.doi.org/10.1093/jn/136.7.2099S. PMid:16772510.
Mao, Y., Mohan, R., Zhang, S., & Tang, X. (2013). MicroRNAs as pharmacological targets in diabetes. Pharmacological Research, 75, 37-47. http://dx.doi.org/10.1016/j.phrs.2013.06.005. PMid:23810798.
Massart, J., Katayama, M., & Krook, A. (2016). microManaging glucose and lipid metabolism in skeletal muscle: Role of microRNAs. Biochimica et Biophysica Acta, 1861(12, 12 Pt B), 2130-2138. http://dx.doi.org/10.1016/j. bbalip.2016.05.006. PMid:27183241.
McFarlane, D., Paradis, M. R., Zimmel, D., Sykes, B., Brorsen, B. W., Sanchez, A., & Vainio, K. (2011). The effect of geographic location, breed, and pituitary dysfunction on seasonal adrenocorticotropin and α-melanocyte-stimulating hormone plasma concentrations in horses. Journal of Veterinary Internal Medicine, 25(4), 872-881. http://dx.doi.org/10.1111/j.1939-1676.2011.0745.x. PMid:21745243.
McGowan, C. M., Frost, R., Pfeiffer, D. U., & Neiger, R. (2004). Serum insulin concentrations in horses with equine Cushing’s syndrome: Response to a cortisol inhibitor and prognostic value. Equine Veterinary Journal, 36(3), 295-298. http://dx.doi.org/10.2746/0425164044877288. PMid:15147141.
Meshkani, R., & Adeli, K. (2009). Hepatic insulin resistance, metabolic syndrome and cardiovascular disease. Clinical Biochemistry, 42(13-14), 1331-1346. http://dx.doi.org/10.1016/j.clinbiochem.2009.05.018. PMid:19501581.
Mestdagh, P., Van Vlierberghe, P., De Weer, A., Muth, D., Westermann, F., Speleman, F., & Vandesompele, J. (2009). A novel and universal method for microRNA RT-qPCR data normalization. Genome Biology, 10(6), R64. http:// dx.doi.org/10.1186/gb-2009-10-6-r64. PMid:19531210.
Metson, A. J., Gibson, E. J., Hunt, J. L. & Saunders, W. M. H. (1979) Seasonal variations in chemical composition of pasture. New Zealand Journal of Agricultural Research, 22(2), 309-318. http://dx.doi.org/10.1080/002882 33.1979.10430752.
Morgan, R., Keen, J., & McGowan, C. (2015). Equine metabolic syndrome. The Veterinary Record, 177(7), 173-179. http://dx.doi.org/10.1136/vr.103226. PMid:26273009.
Nakanishi, N., Nakagawa, Y., Tokushige, N., Aoki, N., Matsuzaka, T., Ishii, K., Yahagi, N., Kobayashi, K., Yatoh, S., Takahashi, A., Suzuki, H., Urayama, O., Yamada, N., & Shimano, H. (2009). The up-regulation of microRNA-335 is associated with lipid metabolism in liver and white adipose tissue of genetically obese mice. Biochemical and Biophysical Research Communications, 385(4), 492-496. http://dx.doi.org/10.1016/j.bbrc.2009.05.058. PMid:19460359.
Nakashima, N., Sharma, P. M., Imamura, T., Bookstein, R., & Olefsky, J. M. (2000). The tumor suppressor PTEN negatively regulates insulin signaling in 3T3-L1 adipocytes. The Journal of Biological Chemistry, 275(17), 12889-12895. http://dx.doi.org/10.1074/jbc.275.17.12889. PMid:10777587.
Nirmalan, N., & Nirmalan, M. (2017). Hormonal control of metabolism: Regulation of plasma glucose. Anaesthesia and Intensive Care Medicine, 18(10), 502-507. http://dx.doi.org/10.1016/j.mpaic.2017.06.019.
Nulton, L. (2014). Cross-kingdom microRNA detection and influence of diet on endogenous equine micrornas [Master thesis, Colorado State University]. 2000-2019 - CSU Theses and Dissertations. https://mountainscholar.org/ handle/10217/100538
Ortega, F. J., Mercader, J. M., Catalán, V., Moreno-Navarrete, J. M., Pueyo, N., Sabater, M., Gómez-Ambrosi, J., Anglada, R., Fernández-Formoso, J. A., Ricart, W., Frühbeck, G., & Fernández-Real, J. M. (2013). Targeting the circulating microRNA signature of obesity. Clinical Chemistry, 59(5), 781-792. http://dx.doi.org/10.1373/ clinchem.2012.195776. PMid:23396142.
Ortega, F. J., Mercader, J. M., Moreno-Navarrete, J. M., Rovira, O., Guerra, E., Esteve, E., Xifra, G., Martínez, C., Ricart, W., Rieusset, J., Rome, S., Karczewska-Kupczewska, M., Straczkowski, M., & Fernández-Real, J. M. (2014). Profiling of circulating microRNAs reveals common microRNAs linked to type 2 diabetes that change with insulin sensitization. Diabetes Care, 37(5), 1375-1383. http://dx.doi.org/10.2337/dc13-1847. PMid:24478399.
Pacholewska, A., Mach, N., Mata, X., Vaiman, A., Schibler, L., Barrey, E., & Gerber, V. (2016). Novel equine tissue miRNAs and breed-related miRNA expressed in serum. BMC Genomics, 17(1), 831. http://dx.doi.org/10.1186/ s12864-016-3168-2. PMid:27782799.
Pando, R., Even-Zohar, N., Shtaif, B., Edry, L., Shomron, N., Phillip, M., & Gat-Yablonski, G. (2012). MicroRNAs in the growth plate are responsive to nutritional cues: Association between miR-140 and SIRT1. The Journal of Nutritional Biochemistry, 23(11), 1474-1481. http://dx.doi.org/10.1016/j.jnutbio.2011.09.010. PMid:22402365.
Pescador, N., Pérez-Barba, M., Ibarra, J. M., Corbatón, A., Martínez-Larrad, M. T., & Serrano-Ríos, M. (2013). Serum circulating microRNA profiling for identification of potential type 2 diabetes and obesity biomarkers. PLoS One, 8(10), e77251. http://dx.doi.org/10.1371/journal.pone.0077251. PMid:24204780.
Pfeifer, M. A., Halter, J. B., & Porte Junior, D. (1981). Insulin secretion in diabetes mellitus. The American Journal of Medicine, 70(3), 579-588. http://dx.doi.org/10.1016/0002-9343(81)90579-9. PMid:7011013.
Piñero, J., Queralt-Rosinach, N., Bravo, À., Deu-Pons, J., Bauer-Mehren, A., Baron, M., Sanz, F., & Furlong, L. I. (2015). DisGeNET: a discovery platform for the dynamical exploration of human diseases and their genes. Database: The Journal of Biological Databases and Curation, 2015, bav028. https://doi.org/10.1093/database/bav028.
Piñero, J., Bravo, À., Queralt-Rosinach, N., Gutiérrez-Sacristán, A., Deu-Pons, J., Centeno, E., García-García, J., Sanz, F., & Furlong, L. I. (2017). DisGeNET: A comprehensive platform integrating information on human disease-associated genes and variants. Nucleic Acids Research, 45(D1), D833-D839. http://dx.doi.org/10.1093/ nar/gkw943. PMid:27924018.
Prabu, P., Rome, S., Sathishkumar, C., Aravind, S., Mahalingam, B., Shanthirani, C. S., Gastebois, C., Villard, A., Mohan, V., & Balasubramanyam, M. (2015). Circulating MiRNAs of ‘Asian Indian Phenotype’ Identified in Subjects with Impaired Glucose Tolerance and Patients with Type 2 Diabetes. PLoS One, 10(5), e0128372. http://dx.doi.org/10.1371/journal.pone.0128372. PMid:26020947.
Rasmussen, J. J., Schou, M., Selmer, C., Johansen, M. L., Gustafsson, F., Frystyk, J., Dela, F., Faber, J., & Kistorp, C. (2017). Insulin sensitivity in relation to fat distribution and plasma adipocytokines among abusers of anabolic androgenic steroids. Clinical Endocrinology, 87(3), 249-256. http://dx.doi.org/10.1111/cen.13372. PMid:28500659.
Reczko, M., Maragkakis, M., Alexiou, P., Grosse, I., & Hatzigeorgiou, A. G. (2012). Functional microRNA targets in protein coding sequences. Bioinformatics (Oxford, England), 28(6), 771-776. http://dx.doi.org/10.1093/ bioinformatics/bts043. PMid:22285563.
Sah, S. P., Singh, B., Choudhary, S., & Kumar, A. (2016). Animal models of insulin resistance: A review. Pharmacological reports: PR, 68(6), 1165-1177. https://doi.org/10.1016/j.pharep.2016.07.010.
Shan, Q., Zheng, G., Zhu, A., Cao, L., Lu, J., Wu, D., Zhang, Z., Fan, S., Sun, C., Hu, B., & Zheng, Y. (2016). Epigenetic modification of miR-10a regulates renal damage by targeting CREB1 in type 2 diabetes mellitus. Toxicology and Applied Pharmacology, 306, 134-143. http://dx.doi.org/10.1016/j.taap.2016.06.010. PMid:27292126.
Shao, Y., Ren, H., Lv, C., Ma, X., Wu, C., & Wang, Q. (2017). Changes of serum Mir-217 and the correlation with the severity in type 2 diabetes patients with different stages of diabetic kidney disease. Endocrine, 55(1), 130-138. http://dx.doi.org/10.1007/s12020-016-1069-4. PMid:27522360.
Sun, J., Li, Z. P., Zhang, R. Q., & Zhang, H. M. (2017). Repression of miR-217 protects against high glucose-induced podocyte injury and insulin resistance by restoring PTEN-mediated autophagy pathway. Biochemical and Biophysical Research Communications, 483(1), 318-324. http://dx.doi.org/10.1016/j.bbrc.2016.12.145. PMid:28017719.
Tai, M. M. (1994). A mathematical model for the determination of total area under glucose tolerance and other metabolic curves. Diabetes Care, 17(2), 152-154. http://dx.doi.org/10.2337/diacare.17.2.152. PMid:8137688.
Tijsen, A. J., Creemers, E. E., Moerland, P. D., de Windt, L. J., van der Wal, A. C., Kok, W. E., & Pinto, Y. M. (2010). MiR423-5p as a circulating biomarker for heart failure. Circulation Research, 106(6), 1035-1039. http://dx.doi. org/10.1161/CIRCRESAHA.110.218297. PMid:20185794.
Trajkovski, M., Hausser, J., Soutschek, J., Bhat, B., Akin, A., Zavolan, M., Heim, M. H., & Stoffel, M. (2011). MicroRNAs 103 and 107 regulate insulin sensitivity. Nature, 474(7353), 649-653. http://dx.doi.org/10.1038/nature10112. PMid:21654750.
Treiber, K. H., Kronfeld, D. S., Hess, T. M., Boston, R. C., & Harris, P. A. (2005). Use of proxies and reference quintiles obtained from minimal model analysis for determination of insulin sensitivity and pancreatic beta-cell responsiveness in horses. American Journal of Veterinary Research, 66(12), 2114-2121. http://dx.doi. org/10.2460/ajvr.2005.66.2114. PMid:16379656.
Vick, M. M., Adams, A. A., Murphy, B. A., Sessions, D. R., Horohov, D. W., Cook, R. F., Shelton, B. J., & Fitzgerald, B. P. (2007). Relationships among inflammatory cytokines, obesity, and insulin sensitivity in the horse. Journal of Animal Science, 85(5), 1144-1155. http://dx.doi.org/10.2527/jas.2006-673. PMid:17264235.
Vlachos, I. S., Zagganas, K., Paraskevopoulou, M. D., Georgakilas, G., Karagkouni, D., Vergoulis, T., Dalamagas, T., & Hatzigeorgiou, A. G. (2015). DIANA-miRPath v3.0: Deciphering microRNA function with experimental support. Nucleic Acids Research, 43(W1), W460-W466. http://dx.doi.org/10.1093/nar/gkv403. PMid:25977294.
Wang, C., Wan, S., Yang, T., Niu, D., Zhang, A., Yang, C., Cai, J., Wu, J., Song, J., Zhang, C. Y., Zhang, C., & Wang, J. (2016). Increased serum microRNAs are closely associated with the presence of microvascular complications in type 2 diabetes mellitus. Scientific Reports, 6(1), 20032. http://dx.doi.org/10.1038/srep20032. PMid:26831044.
Wilcox, G. (2005). Insulin and insulin resistance. The Clinical biochemist. Reviews / Australian Association of Clinical Biochemists, 26(2), 19-39. PMid:16278749.
Williams, M. D., & Mitchell, G. M. (2012). MicroRNAs in insulin resistance and obesity. Experimental Diabetes Research, 2012, 484696. http://dx.doi.org/10.1155/2012/484696. PMid:22851965.
Witwer, K. W. (2012). XenomiRs and miRNA homeostasis in health and disease: Evidence that diet and dietary miRNAs directly and indirectly influence circulating miRNA profiles. RNA Biology, 9(9), 1147-1154. http:// dx.doi.org/10.4161/rna.21619. PMid:22951590.
Yang, W. M., Jeong, H. J., Park, S. W., & Lee, W. (2015). Obesity-induced miR-15b is linked causally to the development of insulin resistance through the repression of the insulin receptor in hepatocytes. Molecular Nutrition & Food Research, 59(11), 2303-2314. http://dx.doi.org/10.1002/mnfr.201500107. PMid:26179126.
[[Q12: Q12]]Yang, W. M., Jeong, H. J., Park, S. Y., & Lee, W. (2014). Saturated fatty acid-induced miR-195 impairs insulin signaling and glycogen metabolism in HepG2 cells. FEBS Letters, 588(21), 3939-3946. http://dx.doi. org/10.1016/j.febslet.2014.09.006. PMid:25240198.
Yang, W. M., Min, K. H., & Lee, W. (2016). MicroRNA expression analysis in the liver of high fat diet-induced obese mice. Data in Brief, 9, 1155-1159. http://dx.doi.org/10.1016/j.dib.2016.11.081. PMid:27995171.
Yi, F., Shang, Y., Li, B., Dai, S., Wu, W., Cheng, L., & Wang, X. (2017). MicroRNA-193-5p modulates angiogenesis through IGF2 in type 2 diabetic cardiomyopathy. Biochemical and Biophysical Research Communications, 491(4), 876-882. http://dx.doi.org/10.1016/j.bbrc.2017.07.108. PMid:28735866.
Ying, W., Tseng, A., Chang, R. C. A., Wang, H., Lin, Y. L., Kanameni, S., Brehm, T., Morin, A., Jones, B., Splawn, T., Criscitiello, M., Golding, M. C., Bazer, F. W., Safe, S., & Zhou, B. (2016). MiR-150 regulates obesity-Associated insulin resistance by controlling B cell functions. Scientific Reports, 6(20176), 20176. http://dx.doi.org/10.1038/ srep20176. PMid:26833392.
Zhou, M., Wang, Q., Sun, J., Li, X., Xu, L., Yang, H., Shi, H., Ning, S., Chen, L., Li, Y., He, T., & Zheng, Y. (2009). In silico detection and characteristics of novel microRNA genes in the Equus caballus genome using an integrated ab initio and comparative genomic approach. Genomics, 94(2), 125-131. http://dx.doi.org/10.1016/j. ygeno.2009.04.006. PMid:19406225.
Zhu, H., & Leung, S. W. (2015). Identification of microRNA biomarkers in type 2 diabetes: A meta-analysis of controlled profiling studies. Diabetologia, 58(5), 900-911. http://dx.doi.org/10.1007/s00125-015-3510-2. PMid:25677225.
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