The Resistance Training Reverses Insulin Resistance in Rats with Periodontitis

Abstract

The present study, aimed to evaluate the effects of resistance training (RT) on glycemia, insulinemia, insulin sensitivity, insulin signaling (IS), and tumor necrosis factor-α (TNF-α) levels in rats with periodontitis. 40 male Wistar rats were distributed into 4 groups: sedentary control group (SCN), exercised control group (ExCN), sedentary ligature-induced periodontal disease group (SPD), and exercised ligature-induced periodontal disease group (ExPD). 28 days after inducing periodontitis the RT started (14-week). Glycemia, insulin, TNF-α levels, and insulin sensitivity were analyzed using various methods. IS was evaluated by measuring tyrosine phosphorylated pp185 in insulin-sensitive tissues (western blot method). Higher levels of insulin, HOMA-IR, and TNF-α, and a decrease in insulin sensitivity were observed in the SPD group, which also had decreased levels of insulin-stimulated tyrosine phosphorylated pp185 in muscle and adipose tissue, when compared to the other groups. The ExPD group had increased levels of insulin-stimulated tyrosine phosphorylated pp185 compared to the SPD group, but showed no significant difference when compared to the SCN and ExCN groups. RT reversed both the insulin resistance (IR) and the IS alterations in rats with induced periodontitis, and decreased the insulin and TNF-α levels. Therefore, the results of show the importance of RT in preventing or reversing IR in rats with periodontitis.

Keywords: Periodontitis, Diabetes Mellitus, Insulin resistance, Tumor necrosis factor-alpha, Resistance training

References

Association, A. D. (2020). 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes—2020. https://doi.org/10.2337/dc20-S002

Astolphi, RD, Curbete, MM, Colombo, NH, Shirakashi, DJ, Chiba, FY, Prieto, AK, Cintra, LT, Bomfim, SR, Ervolino, E., & Sumida, DH (2013). Periapical lesions decrease insulin signal and cause insulin resistance. J Endod, 39(5), 648-652. https://doi.org/10.1016/j.joen.2012.12.031

Bharti, P., Katagiri, S., Nitta, H., Nagasawa, T., Kobayashi, H., Takeuchi, Y., Izumiyama, H., Uchimura, I., Inoue, S., & Izumi, Y. (2013). Periodontal treatment with topical antibiotics improves glycemic control in association with elevated serum adiponectin in patients with type 2 diabetes mellitus. Obes Res Clin Pract, 7(2), e129-e138. https://doi.org/10.1016/j.orcp.2011.11.005

Cabral-Santos, C., de Lima Junior, EA, Fernandes, IMDC, Pinto, RZ, Rosa-Neto, JC, Bishop, NC, & Lira, FS (2019). Interleukin-10 responses from acute exercise in healthy subjects: A systematic review. J Cell Physiol, 234(7), 9956-9965. https://doi.org/10.1002/jcp.27920

Campos, RM, de Mello, MT, Tock, L., Silva, PL, Masquio, DC, de Piano, A., Sanches, PL, Carnier, J., Corgosinho, FC, Foschini, D., Tufik, S., & Dâmaso, AR (2014). Aerobic plus resistance training improves bone metabolism and inflammation in adolescents who are obese. J Strength Cond Res, 28(3), 758-766. https://doi.org/10.1519/JSC.0b013e3182a996df

Carvalho, C.R., Brenelli, S. L., Silva, A. C., Nunes, A. L., Velloso, L. A., & Saad, M. J. (1996). Effect of aging on insulin receptor, insulin receptor substrate-1, and phosphatidylinositol 3-kinase in liver and muscle of rats. Endocrinology, 137(1), 151-159. https://doi.org/10.1210/endo.137.1.8536607

Carvalho-Filho, M. A., Carvalheira, J. B., Velloso, L. A., & Saad, M. J. (2007). [Insulin and angiotensin II signaling pathways cross-talk: implications with the association between diabetes mellitus, arterial hypertension and cardiovascular disease]. Arq Bras Endocrinol Metabol, 51(2), 195-203. https://doi.org/10.1590/s0004-27302007000200008

Chehoud, K. A., Chiba, F. Y., Sassaki, K. T., Garbin, C. A., Sumida, D. H (2008). Effects of fluoride intake on insulin sensitivity and insulin signal transduction. Fluoride, 41, 270-275. https://www.fluorideresearch.org/414/files/FJ2008_v41_n4_p270-275.pdf

Chen, Z., Tian, R., She, Z., Cai, J., & Li, H. (2020). Role of oxidative stress in the pathogenesis of nonalcoholic fatty liver disease. Free Radic Biol Med, 152, 116-141. https://doi.org/10.1016/j.freeradbiomed.2020.02.025

Cho, Y., Ariga, M., Uchijima, Y., Kimura, K., Rho, J. Y., Furuhata, Y., Hakuno, F., Yamanouchi, K., Nishihara, M., & Takahashi, S. (2006). The novel roles of liver for compensation of insulin resistance in human growth hormone transgenic rats. Endocrinology, 147(11), 5374-5384. https://doi.org/10.1210/en.2006-0518

Colombo, N. H., Shirakashi, D. J., Chiba, F. Y., Coutinho, M. S., Ervolino, E., Garbin, C. A., Machado, U. F., & Sumida, D. H. (2012). Periodontal disease decreases insulin sensitivity and insulin signaling. J Periodontol, 83(7), 864-870. https://doi.org/10.1902/jop.2011.110349

Dağ, A., Firat, E. T., Arikan, S., Kadiroğlu, A. K., & Kaplan, A. (2009). The effect of periodontal therapy on serum TNF-alpha and HbA1c levels in type 2 diabetic patients. Aust Dent J, 54(1), 17-22. https://doi.org/10.1111/j.1834-7819.2008.01083.x

del Aguila, L. F., Claffey, K. P., & Kirwan, J. P. (1999). TNF-alpha impairs insulin signaling and insulin stimulation of glucose uptake in C2C12 muscle cells. Am J Physiol, 276(5), E849-855. https://doi.org/10.1152/ajpendo.1999.276.5.E849

Delevatti, R. S., Bracht, C. G., Lisboa, S. D. C., Costa, R. R., Marson, E. C., Netto, N., & Kruel, L. F. M. (2019). The Role of Aerobic Training Variables Progression on Glycemic Control of Patients with Type 2 Diabetes: a Systematic Review with Meta-analysis. Sports Med Open, 5(1), 22. https://doi.org/10.1186/s40798-019-0194-z

Demmer, R. T., Squillaro, A., Papapanou, P. N., Rosenbaum, M., Friedewald, W. T., Jacobs, D. R., & Desvarieux, M. (2012). Periodontal infection, systemic inflammation, and insulin resistance: results from the continuous National Health and Nutrition Examination Survey (NHANES) 1999-2004. Diabetes Care, 35(11), 2235-2242. https://doi.org/10.2337/dc12-0072

Dubé, J. J., Allison, K. F., Rousson, V., Goodpaster, B. H., & Amati, F. (2012). Exercise dose and insulin sensitivity: relevance for diabetes prevention. Med Sci Sports Exerc, 44(5), 793-799. https://doi.org/10.1249/MSS.0b013e31823f679f

Engebretson, S., Chertog, R., Nichols, A., Hey-Hadavi, J., Celenti, R., & Grbic, J. (2007). Plasma levels of tumour necrosis factor-alpha in patients with chronic periodontitis and type 2 diabetes. J Clin Periodontol, 34(1), 18-24. https://doi.org/10.1111/j.1600-051X.2006.01017.x

Falcão-Tebas, F., Marin, E. C., Kuang, J., Bishop, D. J., & McConell, G. K. (2020). Maternal exercise attenuates the lower skeletal muscle glucose uptake and insulin secretion caused by paternal obesity in female adult rat offspring. J Physiol. https://doi.org/10.1113/JP279582

Feinstein, R., Kanety, H., Papa, M. Z., Lunenfeld, B., & Karasik, A. (1993). Tumor necrosis factor-alpha suppresses insulin-induced tyrosine phosphorylation of insulin receptor and its substrates. J Biol Chem, 268(35), 26055-26058. https://www.jbc.org/content/268/35/26055.long

Ferrari, F., Bock, P. M., Motta, M. T., & Helal, L. (2019). Biochemical and Molecular Mechanisms of Glucose Uptake Stimulated by Physical Exercise in Insulin Resistance State: Role of Inflammation. Arq Bras Cardiol, 113(6), 1139-1148. https://doi.org/10.5935/abc.20190224

Figueira, F. R., Umpierre, D., Casali, K. R., Tetelbom, P. S., Henn, N. T., Ribeiro, J. P., & Schaan, B. D. (2013). Aerobic and combined exercise sessions reduce glucose variability in type 2 diabetes: crossover randomized trial. PLoS One, 8(3), e57733. https://doi.org/10.1371/journal.pone.0057733

Geirsdottir, O. G., Arnarson, A., Briem, K., Ramel, A., Jonsson, P. V., & Thorsdottir, I. (2012). Effect of 12-week resistance exercise program on body composition, muscle strength, physical function, and glucose metabolism in healthy, insulin-resistant, and diabetic elderly Icelanders. J Gerontol A Biol Sci Med Sci, 67(11), 1259-1265. https://doi.org/10.1093/gerona/gls096

Geloneze, B., & Tambascia, M. A. (2006). [Laboratorial evaluation and diagnosis of insulin resistance]. Arq Bras Endocrinol Metabol, 50(2), 208-215. https://doi.org/10.1590/s0004-27302006000200007

Hayashi, J., Hasegawa, A., Hayashi, K., Suzuki, T., Ishii, M., Otsuka, H., Yatabe, K., Goto, S., Tatsumi, J., & Shin, K. (2017). Effects of periodontal treatment on the medical status of patients with type 2 diabetes mellitus: a pilot study. BMC Oral Health, 17(1), 77. https://doi.org/10.1186/s12903-017-0369-2

Hayashi, T., Hirshman, M. F., Kurth, E. J., Winder, W. W., & Goodyear, L. J. (1998). Evidence for 5' AMP-activated protein kinase mediation of the effect of muscle contraction on glucose transport. Diabetes, 47(8), 1369-1373. https://doi.org/10.2337/diab.47.8.1369

Ho, S. S., Dhaliwal, S. S., Hills, A. P., & Pal, S. (2013). Effects of chronic exercise training on inflammatory markers in Australian overweight and obese individuals in a randomized controlled trial. Inflammation, 36(3), 625-632. https://doi.org/10.1007/s10753-012-9584-9

Hornberger, T. A., & Farrar, R. P. (2004). Physiological hypertrophy of the FHL muscle following 8 weeks of progressive resistance exercise in the rat. Can J Appl Physiol, 29(1), 16-31. https://doi.org/10.1139/h04-002

Hotamisligil, G. S., Murray, D. L., Choy, L. N., & Spiegelman, B. M. (1994). Tumor necrosis factor alpha inhibits signaling from the insulin receptor. Proc Natl Acad Sci U S A, 91(11), 4854-4858. https://doi.org/10.1073/pnas.91.11.4854

Hotamisligil, G. S., Peraldi, P., Budavari, A., Ellis, R., White, M. F., & Spiegelman, B. M. (1996). IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-alpha- and obesity-induced insulin resistance. Science, 271(5249), 665-668. https://doi.org/10.1126/science.271.5249.665

Hussey, S. E., McGee, S. L., Garnham, A., Wentworth, J. M., Jeukendrup, A. E., & Hargreaves, M. (2011). Exercise training increases adipose tissue GLUT4 expression in patients with type 2 diabetes. Diabetes Obes Metab, 13(10), 959-962. https://doi.org/10.1111/j.1463-1326.2011.01426.x

Jung, Y. S., Shin, M. H., Kweon, S. S., Lee, Y. H., Kim, O. J., Kim, Y. J., Chung, H. J., & Kim, O. S. (2015). Periodontal disease associated with blood glucose levels in urban Koreans aged 50 years and older: the Dong-gu study. Gerodontology, 32(4), 267-273. https://doi.org/10.1111/ger.12107

Katagiri, S., Nitta, H., Nagasawa, T., Izumi, Y., Kanazawa, M., Matsuo, A., Chiba, H., Fukui, M., Nakamura, N., Oseko, F., Kanamura, N., Inagaki, K., Noguchi, T., Naruse, K., Matsubara, T., Miyazaki, S., Miyauchi, T., Ando, Y., Hanada, N., & Inoue, S. (2013). Effect of glycemic control on periodontitis in type 2 diabetic patients with periodontal disease. J Diabetes Investig, 4(3), 320-325. https://doi.org/10.1111/jdi.12026

Kennedy, JW, Hirshman, MF, Gervino, EV, Ocel, JV, Forse, RA, Hoenig, SJ, Aronson, D., Goodyear, LJ, & Horton, ES (1999). Acute exercise induces GLUT4 translocation in skeletal muscle of normal human subjects and subjects with type 2 diabetes. Diabetes, 48(5), 1192-1197. https://doi.org/10.2337/diabetes.48.5.1192

Lauterbach, M. A., & Wunderlich, F. T. (2017). Macrophage function in obesity-induced inflammation and insulin resistance. Pflugers Arch, 469(3-4), 385-396. https://doi.org/10.1007/s00424-017-1955-5

Machado, A. C., Quirino, M. R., & Nascimento, L. F. (2005). Relation between chronic periodontal disease and plasmatic levels of triglycerides, total cholesterol and fractions. Braz Oral Res, 19(4), 284-289. https://doi.org/10.1590/s1806-83242005000400009

Mackenzie, R., Maxwell, N., Castle, P., Elliott, B., Brickley, G., & Watt, P. (2012). Intermittent exercise with and without hypoxia improves insulin sensitivity in individuals with type 2 diabetes. J Clin Endocrinol Metab, 97(4), E546-555. https://doi.org/10.1210/jc.2011-2829

Malone, J. I., & Hansen, B. C. (2019). Does obesity cause type 2 diabetes mellitus (T2DM)? Or is it the opposite? Pediatr Diabetes, 20(1), 5-9. https://doi.org/10.1111/pedi.12787

Marinho, R., Ropelle, ER, Cintra, DE, De Souza, CT, Da Silva, AS, Bertoli, FC, Colantonio, E., D'Almeida, V., & Pauli, JR (2012). Endurance exercise training increases APPL1 expression and improves insulin signaling in the hepatic tissue of diet-induced obese mice, independently of weight loss. J Cell Physiol, 227(7), 2917-2926. https://doi.org/10.1002/jcp.23037

Mattera, MSLC, Chiba, FY, Lopes, FL, Tsosura, TVS, Peres, MA, Brito, VGB, de Oliveira, SHP, Pereira, RF, Marani, F., Dos Santos, RM, Belardi, BE, Tessarin, GWL, Benites, ML, Ervolino, E., Heimann, JC, & Sumida, DH (2019). Effect of maternal periodontitis on GLUT4 and inflammatory pathway in adult offspring. J Periodontol. https://doi.org/10.1002/JPER.18-0568

Mavros, Y., Kay, S., Anderberg, KA, Baker, MK, Wang, Y., Zhao, R., Meiklejohn, J., Climstein, M., O'Sullivan, A., de Vos, N., Baune, BT, Blair, SN, Simar, D., Rooney, K., Singh, N., & Fiatarone Singh, MA (2013). Changes in insulin resistance and HbA1c are related to exercise-mediated changes in body composition in older adults with type 2 diabetes: interim outcomes from the GREAT2DO trial. Diabetes Care, 36(8), 2372-2379. https://doi.org/10.2337/dc12-2196

Mealey, B. L., & Ocampo, G. L. (2007). Diabetes mellitus and periodontal disease. Periodontol 2000, 44, 127-153. https://doi.org/10.1111/j.1600-0757.2006.00193.x

Oliveira, AG, Carvalho, BM, Tobar, N., Ropelle, ER, Pauli, JR, Bagarolli, RA, Guadagnini, D., Carvalheira, JB, & Saad, MJ (2011). Physical exercise reduces circulating lipopolysaccharide and TLR4 activation and improves insulin signaling in tissues of DIO rats. Diabetes, 60(3), 784-796. https://doi.org/10.2337/db09-1907

Panveloski-Costa, A. C., Pinto Júnior, D. A., Brandão, B. B., Moreira, R. J., Machado, U. F., & Seraphim, P. M. (2011). [Resistive training reduces inflammation in skeletal muscle and improves the peripheral insulin sensitivity in obese rats induced by hyperlipidic diet]. Arq Bras Endocrinol Metabol, 55(2), 155-163. https://doi.org/10.1590/S0004-27302011000200008

Pauli, JR, Ropelle, ER, Cintra, DE, Carvalho-Filho, MA, Moraes, JC, De Souza, CT, Velloso, LA, Carvalheira, JB, & Saad, MJ (2008). Acute physical exercise reverses S-nitrosation of the insulin receptor, insulin receptor substrate 1 and protein kinase B/Akt in diet-induced obese Wistar rats. J Physiol, 586(2), 659-671. https://doi.org/10.1113/jphysiol.2007.142414

Petersen, A. M., & Pedersen, B. K. (2005). The anti-inflammatory effect of exercise. J Appl Physiol (1985), 98(4), 1154-1162. https://doi.org/10.1152/japplphysiol.00164.2004

Phillips, M. D., Flynn, M. G., McFarlin, B. K., Stewart, L. K., & Timmerman, K. L. (2010). Resistance training at eight-repetition maximum reduces the inflammatory milieu in elderly women. Med Sci Sports Exerc, 42(2), 314-325. https://doi.org/10.1249/MSS.0b013e3181b11ab7

Pontes Andersen, C. C., Buschard, K., Flyvbjerg, A., Stoltze, K., & Holmstrup, P. (2006). Periodontitis deteriorates metabolic control in type 2 diabetic Goto-Kakizaki rats. J Periodontol, 77(3), 350-356. https://doi.org/10.1902/jop.2006.050184

Shoelson, S. E., Lee, J., & Goldfine, A. B. (2006). Inflammation and insulin resistance. J Clin Invest, 116(7), 1793-1801. https://doi.org/10.1172/JCI29069

Sun, W. L., Chen, L. L., Zhang, S. Z., Wu, Y. M., Ren, Y. Z., & Qin, G. M. (2011). Inflammatory cytokines, adiponectin, insulin resistance and metabolic control after periodontal intervention in patients with type 2 diabetes and chronic periodontitis. Intern Med, 50(15), 1569-1574. https://doi.org/10.2169/internalmedicine.50.5166

van der Poll, T., Coyle, S. M., Moldawer, L. L., & Lowry, S. F. (1996). Changes in endotoxin-induced cytokine production by whole blood after in vivo exposure of normal humans to endotoxin. J Infect Dis, 174(6), 1356-1360. https://doi.org/10.1093/infdis/174.6.1356

Whyte, L. J., Ferguson, C., Wilson, J., Scott, R. A., & Gill, J. M. (2013). Effects of single bout of very high-intensity exercise on metabolic health biomarkers in overweight/obese sedentary men. Metabolism, 62(2), 212-219. https://doi.org/10.1016/j.metabol.2012.07.019

Wu, Y., Wu, T., Wu, J., Zhao, L., Li, Q., Varghese, Z., Moorhead, J. F., Powis, S. H., Chen, Y., & Ruan, X. Z. (2013). Chronic inflammation exacerbates glucose metabolism disorders in C57BL/6J mice fed with high-fat diet. J Endocrinol, 219(3), 195-204. https://doi.org/10.1530/JOE-13-0160

Yaribeygi, H., Farrokhi, F. R., Butler, A. E., & Sahebkar, A. (2019). Insulin resistance: Review of the underlying molecular mechanisms. J Cell Physiol, 234(6), 8152-8161. https://doi.org/10.1002/jcp.27603

Zhang, J., Gao, Z., Yin, J., Quon, M. J., & Ye, J. (2008). S6K directly phosphorylates IRS-1 on Ser-270 to promote insulin resistance in response to TNF-(alpha) signaling through IKK2. J Biol Chem, 283(51), 35375-35382. https://doi.org/10.1074/jbc.M806480200

Published
2021-02-13
How to Cite
Mota, M. S. de O. da, Mattera, M. S. de L. C., Tsosura, T. V. S., Chiba, F. Y., Pereira, R. F., Bonilha, J. C., Ervolino, E., Belardi, B. E., Santos, R. M. dos, Tavares, B. S., Dourado, N. G., Carnevalli, A. C. N., Santelli, J. O., Sampaio, H. M., Oliveira, R. A. F. de, & Matsushita, D. H. (2021). The Resistance Training Reverses Insulin Resistance in Rats with Periodontitis. Lecturas: Educación Física Y Deportes, 25(273), 97-113. https://doi.org/10.46642/efd.v25i273.2371
Section
Research Articles