Investigation effect of 12-week High-Intensity Interval Training FOXO1 Gene Expression of Subcutaneous Adipose Tissue and Insulin Resistance in Type 2 Diabetic Rats

Author
afzal almasi
Abstract
Background and Objectives: Studies have pointed to the possible role of FOXO1 in the pathogenesis of type 2 diabetes, due to the claim that it affects glycemic control and lipid metabolism. The aim of this study was to investigate the effect of 12 weeks of high-intensity interval (HIIT) on FOXO1 expression in subcutaneous adipose tissue, insulin resistance, insulin resistance, and blood glucose in type 2 diabetic rats.

Materials and Methods: This is a fundamental and experimental research. The statistical population of this study is all male Wistar rats of Pasteur Institute of Iran. Among them, 14 male Wistar 10 week old rats weighing 220 ± 20 gr Randomized method was used to participate in the study. After a fasting night (12 hours), rats were diabetic by injection of nicotinamide and streptozotocin and divided into 2 groups of HIIT training and control. 12-week exercises were performed in 5 sessions of 30 minutes per week in the running of the treadmill with 1-minute repetitions and 2-minute active rest. The untrained diabetic group did not attend any exercise program. 48 hours after the last training session, the rats were anesthetized and slaughtered. A t-test was used for statistical analysis.

Results: 12 weeks of periodic exercise decreased the relative expression of FOXO1 in comparison with the control group (P = 0.033). However, there was no significant difference in insulin resistance between the two groups (P = 0.921), but glucose and insulin decreased significantly with 12 weeks of periodic exercise (P = 0.001).

Conclusion: 12 weeks of HIIT training leads to a decrease in blood glucose levels, despite the lack of insulin resistance in type 2 diabetic rats. This improvement can be attributed somewhat to signaling pathways dependent on changes in the expression of FOXO1 independent of insulin resistance.
Keywords
FOXO1
Type 2 Diabetes
Insulin Resistance
Rats
Lazar MA. How obesity causes diabetes: not a tall tale. Science 2005;307(5708):373-5.
Ruchat S-M, Rankinen T, Weisnagel S, Rice T, Rao D, Bergman R, et al. Improvements in glucose homeostasis in response to regular exercise are influenced by the PPARG Pro12Ala variant: results from the HERITAGE Family Study. Diabetologia 2010;53(4):679-89.
Schick EE. The effect of FoxO1 on glycemic control and skeletal muscle glucose uptake and lipid metabolism [Dissertation]. The University of Toledo, 2014.
Jing E, Gesta S, Kahn CR. SIRT2 regulates adipocyte differentiation through FoxO1 acetylation/deacetylation. Cell Metab 2007;6(2):105-14.
Calnan D, Brunet A. The foxO code. Oncogene 2008;27(16):2276-88.
Chakrabarti P, Kandror KV. FoxO1 controls insulin-dependent adipose triglyceride lipase (ATGL) expression and lipolysis in adipocytes. J Biol Chem 2009;284(20):13296-300.
Fan W, Imamura T, Sonoda N, Sears DD, Patsouris D, Kim JJ, et al. FOXO1 transrepresses peroxisome proliferator-activated receptor γ transactivation, coordinating an insulin-induced feed-forward response in adipocytes. J BIOL CHEM 2009;284(18):12188-97.
Sanchez AM. FoxO transcription factors and endurance training: a role for FoxO1 and FoxO3 in exercise‐induced angiogenesis. J Physiol 2015;593(2):363-4.
Azad M, Khaledi N, Hedayati M. Effect of acute and chronic eccentric exercise on FOXO1 mRNA expression as fiber type transition factor in rat skeletal muscles. Gene 2016;584(2):180-4.
Gibala MJ. High-intensity interval training: New insights. Sports Science Exchange 2007;20(2):1-5.
Shaban N, Kenno KA, Milne KJ. The effects of a 2 week modified high intensity interval training program on the homeostatic model of insulin resistance (HOMA-IR) in adults with type 2 diabetes. J Sports Med Phys Fitness 2014;54(2):203-9.
Karstoft K, Winding K, Knudsen SH, James NG, Scheel MM, Olesen J, et al. Mechanisms behind the superior effects of interval vs continuous training on glycaemic control in individuals with type 2 diabetes: a randomised controlled trial. Diabetologia 2014;57(10):2081-93.
Wei M, Ong L, Smith MT, Ross FB, Schmid K, Hoey AJ, et al. The streptozotocin‐diabetic rat as a model of the chronic complications of human diabetes. Heart Lung Circ 2003;12(1):44-50.
Ghaffari m, salemi z, goodarzi m, ghaasemi m, rafee e: comparison of serum visfatin levels in restricted diet rats, type2 diabetic rats and insulin resistance rats with normal rats. J Fasa Univ Med Sci 2015;5(3):435-43.
Takhshid MA, Ghasemi M: Methods for assessing insulin sensitivity and resistance. Journal of Laboratory & Diagnosis 2014;6(23):8-13.
Sheu WHH, Chang TM, Lee WJ, Ou HC, Wu CM, Tseng LN, et al. Effect of weight loss on proinflammatory state of mononuclear cells in obese women. Obesity 2008;16(5):1033-8.
Goldhaber-Fiebert JD, Goldhaber-Fiebert SN, Tristán ML, Nathan DM. Randomized controlled community-based nutrition and exercise intervention improves glycemia and cardiovascular risk factors in type 2 diabetic patients in rural Costa Rica. Diabetes care 2003;26(1):24-9.
Ligtenberg PC, Hoekstra JB, Bol E, Zonderland ML, Erkelens DW. Effects of physical training on metabolic control in elderly type 2 diabetes mellitus patients. Clin Sci 1997;93(2):127-35.
Vancea DMM, Vancea JN, Pires MIF, Reis MA, Moura RB, Dib SA. Effect of frequency of physical exercise on glycemic control and body composition in type 2 diabetic patients. Arq Bras Cardiol 2009;92(1):23-30.
Steckling FM, Farinha JB, Santos DL, Bresciani G, Mortari JA, Stefanello ST, et al. High Intensity Interval Training Reduces the Levels of Serum Inflammatory Cytokine on Women with Metabolic Syndrome. Exp Clin Endocrinol Diabetes 2016;124(10):597-601.
Koebnick C, Wagner K, Garcia A, Gruendel S, Lahmann P, Weickert M, et al. Increase in serum resistin during weight loss in overweight subjects is related to lipid metabolism. Int J Obes 2006;30(7):1097-103.
Leggate M, Carter WG, Evans MJ, Vennard RA, Sribala-Sundaram S, Nimmo MA. Determination of inflammatory and prominent proteomic changes in plasma and adipose tissue after high-intensity intermittent training in overweight and obese males. J Appl Physiol 2012;112(8):1353-60.
Lakhdar N, Saad HB, Denguezli M, Zaouali M, Zbidi A, Tabka Z, et al. Effects of intense cycling training on plasma leptin and adiponectin and its relation to insulin resistance. Neuro Endocrinol Lett 2013;34(3):229-35.
Abd El-Kader S, Gari A, Salah El-Den A. Impact of moderate versus mild aerobic exercise training on inflammatory cytokines in obese type 2 diabetic patients: a randomized clinical trial. Afr Health Sci 2013;13(4):857-63.
Okamoto H, Hribal ML, Lin HV, Bennett WR, Ward A, Accili D. Role of the forkhead protein FoxO1 in β cell compensation to insulin resistance. J Clin Invest 2006; 116(3):775-82.
Frøsig C, Rose AJ, Treebak JT, Kiens B, Richter EA, Wojtaszewski JF. Effects of endurance exercise training on insulin signaling in human skeletal muscle: interactions at the level of phosphatidylinositol 3-kinase, Akt, and AS160. Diabetes 2007;56(8):2093-102.
Tjønna AE, Lee SJ, Rognmo Ø, Stølen TO, Bye A, Haram PM, et al. Aerobic interval training versus continuous moderate exercise as a treatment for the metabolic syndrome: a pilot study. Circulation 2008;118(4):346-54.