Daneshvar Medicine

Daneshvar Medicine

The effect of eight-week high intensity interval training (HIIT) and caffeine consumption on glycogen synthase expression and hepatic glycogen levels in diabetic rats

Document Type : Original Article

Authors
Moin Norozi 1
Abbas Sadeghi 2
Mohadesh Faal Pakdehi 3
Ghasem Torabi 4
1 Allameh Qazvini Institute of Higher Education, Qazvin, Iran
2 Department of Sports Sciences, Faculty of Social Sciences, Imam Khomeini International University, Qazvin, Iran
3 Department of Sports Sciences, Faculty of Social Sciences, Imam Khomeini International University
4 Department of Sports Sciences Ayatollah Amoli University, Amol, Iran
10.22070/daneshmed.2021.14819.1101
Abstract
Background and Objective: Diabetes is a common metabolic disease that leads to impaired hepatic glycogen synthesis. The present study investigates the effect of eight weeks of intense intermittent exercise (HIIT) and caffeine consumption on glycogen synthase (GYS2) expression and liver glycogen levels in diabetic rats.
Materials and Methods: In an experimental clinical-intervention study, 50 streptozotocin-induced diabetic rats were divided into 5 equal groups of control (C), diabetic (D), supplemental diabetic (D + CAF), diabetic with exercise (D + T), supplement and exercise (D + CAF + T). The training program consisted of eight weeks, 5 sessions per week (6 to 12 2-minute sessions with an intensity of 85-90% of the maximum speed) and 70 mg/kg of caffeine were injected five days a week. After anesthesia, liver tissue was extracted and the expression levels of (GYS2) and liver glycogen were assessed. Data analysis was performed by independent t-test and two-way ANOVA at a significant level of (P<0.05).
Results: Induction of diabetes significantly reduced hepatic glycogen and GYS2 expression (P<0.001). Also, caffeine consumption (P<0.01) and HIIT (P=0.024) both significantly increased GYS2, which had a greater effect of caffeine with a 44% effect size. Also, HIIT (P=0.529) and caffeine (P=0.761) neither alone, nor in combination (P=0.12) caused a significant increase in hepatic glycogen.
Conclusion: According to results, it is possible to suggest HIIT and caffeine consumption as an effective intervention to improve (GYS2) expression. However, a clear statement requires further research in this area.
Keywords
High intensity interval training (HIIT)
Caffeine
Diabetes
Glycogen
Glycogen synthase
  1. Association AD. Prevention or delay of type 2 diabetes: standards of medical care in diabetes—2019. Diabetes Care 2019;42(Supplement 1):S29-S33.
  2. Wang L, Liu Q, Wang M, Du Y, Tan X, Xu B, et al. Effects of fasting on liver glycogen structure in rats with type 2 diabetes. Carbohydrate Polymers 2020;237:116144.
  3. Fan X, Tao J, Zhou Y, Hou Y, Wang Y, et al. Investigations on the effects of ginsenoside-Rg1 on glucose uptake and metabolism in insulin resistant HepG2 cells. European Journal of Pharmacology 2019; 843:277-84.
  4. Irimia JM, Meyer CM, Peper CL, Zhai L, Bock CB, Previs SF, et al. Impaired glucose tolerance and predisposition to the fasted state in liver glycogen synthase knock-out mice. Journal of Biological Chemistry. 2010; 285(17):12851-61.
  5. Kollberg G, Tulinius M, Gilljam T, Östman-Smith I, Forsander G, Jotorp P, et al. Cardiomyopathy and exercise intolerance in muscle glycogen storage disease 0. New England Journal of Medicine 2007; 357(15):1507-14.
  6. Chown EE, Wang P, Zhao X, Crowder JJ, Strober JW, Sullivan MA, et al. GYS1 or PPP1R3C deficiency rescues murine adult polyglucosan body disease. Annals of Clinical and Translational Neurology 2020; 7(11):2186-98.
  7. Arko JJ, Debeljak M, Tansek MZ, Battelino T, Groselj U. A patient with glycogen storage disease type 0 and a novel sequence variant in GYS2: a case report and literature review. Journal of International Medical Research 2020; 48(8):0300060520936857.
  8. Roach PJ, Depaoli-Roach AA, Hurley TD, Tagliabracci VS. Glycogen and its metabolism: some new developments and old themes. Biochemical Journal 2012; 441(3):763-87.
  9. Huang X, Vaag A, Hansson M, Weng J, Laurila ES, Groop L. Impaired insulin-stimulated expression of the glycogen synthase gene in skeletal muscle of type 2 diabetic patients is acquired rather than inherited. The Journal of Clinical Endocrinology & Metabolism 2000; 85(4):1584-90.
  10. Nilsson E, Jansson PA, Perfilyev A, Volkov P, Pedersen M, Svensson MK, et al. Altered DNA methylation and differential expression of genes influencing metabolism and inflammation in adipose tissue from subjects with type 2 diabetes. Diabetes 2014 ;63(9):2962-76.
  11. Orho M, Bosshard NU, Buist NR, Gitzelmann R, Aynsley-Green A, Blümel P, et al. Mutations in the liver glycogen synthase gene in children with hypoglycemia due to glycogen storage disease type 0. The Journal of Clinical Investigation 1998;102(3):507-15.
  12. Doi R, Oishi K, Ishida N. CLOCK regulates circadian rhythms of hepatic glycogen synthesis through transcriptional activation of Gys2. Journal of Biological Chemistry 2010; 285(29):22114-21.
  13. Kleinert M, Sylow L, Richter EA. Regulation of glycogen synthase in muscle and its role in Type 2 diabetes. Diabetes Management 2013; 3(1):81.
  14. Weng TP, Huang SC, Chuang YF, Wang JS. Effects of interval and continuous exercise training on CD4 lymphocyte apoptotic and autophagic responses to hypoxic stress in sedentary men. PloS One 2013;8(11):e80248.
  15. Kraniou Y, Cameron-Smith D, Misso M, Collier G, Hargreaves M. Effects of exercise on GLUT-4 and glycogenin gene expression in human skeletal muscle. Journal of Applied Physiology 2000;88(2):794-6.
  16. Wedick NM, Brennan AM, Sun Q, Hu FB, Mantzoros CS, van Dam RM. Effects of caffeinated and decaffeinated coffee on biological risk factors for type 2 diabetes: a randomized controlled trial. Nutrition Journal 2011;10(1):1-9.
  17. Magkos F, Kavouras SA. Caffeine use in sports, pharmacokinetics in man, and cellular mechanisms of action. Critical Reviews in Food Science and Nutrition 2005;45(7-8):535-62.
  18. Akash MS, Rehman K, Chen S. Effects of coffee on type 2 diabetes mellitus. Nutrition 2014;30(7-8):755-63.
  19. MacKenzie T, Comi R, Sluss P, Keisari R, Manwar S, Kim J, et al. Metabolic and hormonal effects of caffeine: randomized, double-blind, placebo-controlled crossover trial. Metabolism 2007;56(12):1694-8.
  20. Gilboe DP, Nuttall FQ. The synergistic action of caffeine or adenosine on glucose stimulation of liver glycogen synthase phosphatase activity. FEBS letters 1984;170(2):365-9.
  21. Sasidharan SR, Joseph JA, Anandakumar S, Venkatesan V, Ariyattu Madhavan CN, Agarwal A. An experimental approach for selecting appropriate rodent diets for research studies on metabolic disorders. BioMed Research International 2013.
  22. Francis SH, Sekhar KR, Ke H, Corbin JD. Inhibition of cyclic nucleotide phosphodiesterases by methylxanthines and related compounds. Methylxanthines 2011:93-133.
  23. Wahren J, Ekberg K. Splanchnic regulation of glucose production. Annual Review of Nutrition 2007; 27:329-45.
  24. Akash MS, Rehman K, Liaqat A. Tumor necrosis factor‐alpha: role in development of insulin resistance and pathogenesis of type 2 diabetes mellitus. Journal of Cellular Biochemistry 2018;119(1):105-10.
  25. Jensen J, Lai YC. Regulation of muscle glycogen synthase phosphorylation and kinetic properties by insulin, exercise, adrenaline and role in insulin resistance. Archives of Physiology and Biochemistry 2009;115(1):13-21.
  26. Dela F, Ingersen A, Andersen NB, Nielsen MB, Petersen HH, Hansen CN, Larsen S, et al. Effects of one‐legged high‐intensity interval training on insulin‐mediated skeletal muscle glucose homeostasis in patients with type 2 diabetes. Acta Physiologica 2019;226(2):e13245.
  27. Hinds TD, Creeden JF, Gordon DM, Spegele AC, Britton SL, Koch LG, et al. Rats genetically selected for high aerobic exercise capacity have elevated plasma bilirubin by upregulation of hepatic biliverdin reductase-A (BVRA) and suppression of UGT1A1. Antioxidants 2020;9(9):889.
  28. Kyun S, Yoo C, Hashimoto T, Tomi H, Teramoto N, Kim J, et al. Effects of exogenous lactate administration on fat metabolism and glycogen synthesis factors in rats. Physical Activity and Nutrition 2020;24(2):1.
  29. Christ-Roberts CY, Pratipanawatr T, Pratipanawatr W, Berria R, Belfort R, Mandarino LJ. Increased insulin receptor signaling and glycogen synthase activity contribute to the synergistic effect of exercise on insulin action. Journal of Applied Physiology 2003;95(6):2519-29.
  30. Khosravi M, Tayebi SM, Safari H. Single and concurrent effects of endurance and resistance training on pulmonary function. Iranian Journal of Basic Medical Sciences 2013;16(4):628.
  31. Wang Y, Wen L, Zhou S, Zhang Y, Wang XH, He YY, et al. Effects of four weeks intermittent hypoxia intervention on glucose homeostasis, insulin sensitivity, GLUT4 translocation, insulin receptor phosphorylation, and Akt activity in skeletal muscle of obese mice with type 2 diabetes. PLoS One 2018;13(9):e0203551.
  32. Hingst JR, Bruhn L, Hansen MB, Rosschou MF, Birk JB, Fentz J, et al. Exercise-induced molecular mechanisms promoting glycogen supercompensation in human skeletal muscle. Molecular Metabolism 2018;16:24-34.
  33. Jensen J, Tantiwong P, Stuenæs JT, Molina-Carrion M, DeFronzo RA, Sakamoto K, et al. Effect of acute exercise on glycogen synthase in muscle from obese and diabetic subjects. American Journal of Physiology-Endocrinology and Metabolism 2012;303(1):E82-9.
  34. Christ-Roberts CY, Pratipanawatr T, Pratipanawatr W, Berria R, Belfort R, Kashyap S, et al. Exercise training increases glycogen synthase activity and GLUT4 expression but not insulin signaling in overweight nondiabetic and type 2 diabetic subjects. Metabolism 2004;53(9):1233-42.
  35. da Silva DE, Grande AJ, Roever L, Tse G, Liu T, Biondi-Zoccai G, et al. High-intensity interval training in patients with type 2 diabetes mellitus: a systematic review. Current Atherosclerosis Reports 2019;21(2):8.
  36. Wormgoor SG, Dalleck LC, Zinn C, Harris NK. Effects of high-intensity interval training on people living with type 2 diabetes: a narrative review. Canadian Journal of Diabetes 2017;41(5):536-47.
  37. James DE, Kraegen EW. The effect of exercise training on glycogen, glycogen synthase and phosphorylase in muscle and liver. European Journal of Applied Physiology and Occupational Physiology 1984;52(3):276-81.
  38. Fuchs CJ, Gonzalez JT, Beelen M, Cermak NM, Smith FE, Thelwall PE, et al. Sucrose ingestion after exhaustive exercise accelerates liver, but not muscle glycogen repletion compared with glucose ingestion in trained athletes. Journal of Applied Physiology 2016; 120(11):1328-34.
  39. Muller GY, de Amo AH, Vedovelli KS, Mariano IR, Bueno GC, Furlan JP, et al. Resistance High-Intensity Interval Training (HIIT) Improves Acute Gluconeogenesis from Lactate in Mice. American Journal of Sports Science 2019;7(2):53-9.
  40. Tarigan EB, Herawati D, Giriwono PE. Komponen bioaktif kopi berpotensi sebagai antidiabetes/the potency of bioactive compounds of coffee as antidiabetis. Perspektif 2020;19(1):41-52.
  41. Loureiro LM, Reis CE, da Costa TH. Effects of coffee components on muscle glycogen recovery: a systematic review. International Journal of Sport Nutrition and Exercise Metabolism 2018;28(3):284-93.
  42. Gilboe DP, Nuttall FQ. Stimulation of liver glycogen particle synthase D phosphatase activity by caffeine, AMP, and glucose 6-phosphate. Archives of Biochemistry and Biophysics 1982;219(1):179-85.
  43. Battram DS, Shearer J, Robinson D, Graham TE. Caffeine ingestion does not impede the resynthesis of proglycogen and macroglycogen after prolonged exercise and carbohydrate supplementation in humans. Journal of Applied Physiology 2004;96(3):943-50.
  44. Pedersen DJ, Lessard SJ, Coffey VG, Churchley EG, Wootton AM, Ng T, et al. High rates of muscle glycogen resynthesis after exhaustive exercise when carbohydrate is coingested with caffeine. Journal of Applied Physiology. 2008 ;105(1):7-13.
  45. Alkhatib A, Hsieh MJ, Kuo CH, Hou CW. Caffeine optimizes hiit benefits on obesity-associated metabolic adversity in women. Medicine and Science in Sports and Exercise 2020 ;52(8):1793-1800.
  46. Taylor C, Higham D, Close GL, Morton JP. The effect of adding caffeine to postexercise carbohydrate feeding on subsequent high-intensity interval-running capacity compared with carbohydrate alone. International Journal of Sport Nutrition and Exercise Metabolism 2011;21(5):410-6.
Daneshvar Medicine
Volume 29, Issue 5 - Serial Number 156
November and December 2021
Pages 41-55