Document Type : Research Paper I Open Access I Released under (CC BY-NC) license
Authors
1 PhD Student in Exercise Physiology
2 Associate Professor, Department of Sport Physiology, Ayatollah Amoli Branch, Islamic Azad University
Abstract
Aim: : In type 2 diabetes patients, the level of incretins is reduced. Incretins play an important role in glucose homeostasis. The aim of this study was to examine the effect of aerobic training along with Momordica charantia L on serum incretin levels in man with type 2 diabetes.
Method: In this study, 36 men with type 2 diabetes (age 53.08±5.15 years, wight 78.08±6.53kg and BMI 26.22±1.2218 kg/square meters) were selected and were randomly divided into four groups (Control-Water, Control-Momordica charantia, Control-Training and Momordica charantia+Training). The training groups participated in a progressive aerobic training for eight weeks, three sessions a week (running with 40% to 70% of the reserved heart rate and for 15 to 45 min). The groups of Control-Momordica charantia and Momordica charantia+Training were provided 2000 mg of Momordica charantia (In 500 mg capsules) for eight weeks (Twice a day before breakfast and dinner). Two days before and after the protocol, blood samples were taken in fasting state.
Results: The results showed that the GLP-1 I and GIP Increased significantly in all experimental group compared to the control group. (Respectively p=0.000 and p=0.000), Also a significant increase in GLP-1 in Momordica charantia+Training compared to the Momordica charantia and GLP-1 in Momordica charantia+Training compared to the Momordica charantia and Training. Other results showed a significant increase in GLP-1 and GIP in all experimental groups compared to pre-tes (p≤0.05).
Conclusion: It seems that aerobic training and Momordica charantia and combination of both, It improves the factors affecting glycemic control in men with type 2 diabetes.
Keywords
- Abbasi, D. A., Eshaghi, R., Ahmadi, M., & Kohanpour, M. A. (2017). The Effect of a Resistance Training Period on Serum Levels of GIucagon-Like Peptide -1, Dipeptidyl Peptidyl Peptidase-4 and Insulin Resistance in Obese Men.Physiologhy of sport and physical activity. 10(1), 21-29.
- Abraham, K. A., Kearney, M. L., Reynolds, L. J., & Thyfault, J. P. (2016). Red wine enhances glucose-dependent insulinotropic peptide (GIP) and insulin responses in type 2 diabetes during an oral glucose tolerance test. Diabetology international, 7(2), 173-180.
- Ahmed, I., Adeghate, E., Sharma, A., Pallot, D., & Singh, J. (1998). Effects of Momordica charantia fruit juice on islet morphology in the pancreas of the streptozotocin-diabetic rat. Diabetes research and clinical practice, 40(3), 145-151.
- Allen, J. M., Mailing, L. J., Niemiro, G. M., Moore, R., Cook, M. D., White, B. A., . . . Woods, J. A. (2018). Exercise alters gut microbiota composition and function in lean and obese humans. Med Sci Sports Exerc, 50(4), 747-757.
- Association, A. D. (2014). Standards of medical care in diabetes—2014. Diabetes Care, 37(Supplement 1), S14-S80.
- Bhat, G. A., Khan, H. A., Alhomida, A. S., Sharma, P., Singh, R., & Paray, B. A. (2018). GLP-I secretion in healthy and diabetic Wistar rats in response to aqueous extract of Momordica charantia. BMC complementary and alternative medicine, 18(1), 162.
- Broom, D. R., Batterham, R. L., King, J. A., & Stensel, D. J. (2009). Influence of resistance and aerobic exercise on hunger, circulating levels of acylated ghrelin, and peptide YY in healthy males. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 296(1), R29-R35.
- Brown, J., Dryburgh, J., Ross, S., & Dupre, J. (1975). Identification and actions of gastric inhibitory polypeptide. Paper presented at the Proceedings of the 1974 Laurentian Hormone Conference.
- Brubaker, P., & Drucker, D. (2002). Structure-function of the glucagon receptor family of G protein-coupled receptors: the glucagon, GIP, GLP-1, and GLP-2 receptors. Receptors and Channels, 8(3-4), 179-188.
10. Cheng, H.-L., Huang, H.-K., Chang, C.-I., Tsai, C.-P., & Chou, C.-H. (2008). A cell-based screening identifies compounds from the stem of Momordica charantia that overcome insulin resistance and activate AMP-activated protein kinase. Journal of Agricultural and Food Chemistry, 56(16), 6835-6843.
11. Christensen, M., Vedtofte, L., Holst, J. J., Vilsbøl, T., & Knop, F. K. (2011). Glucose-dependent insulinotropic polypeptide: a bifunctional glucose-dependent regulator of glucagon and insulin secretion in humans. Diabetes, DB_110979.
12. Cicero, A. F., & Tartagni, E. (2012). Antidiabetic properties of berberine: from cellular pharmacology to clinical effects. Hospital Practice, 40(2), 56-63.
13. Cortez-Navarrete, M., Martínez-Abundis, E., Pérez-Rubio, K. G., González-Ortiz, M., & Villar, M. M.-d. (2018). Momordica charantia Administration Improves Insulin Secretion in Type 2 Diabetes Mellitus. Journal of medicinal food, 21(7),672-677.
14. Drucker, D. J. (2006). The biology of incretin hormones. Cell metabolism, 3(3), 153-165.
15. Drucker, D. J., Philippe, J., Mojsov, S., Chick, W. L., & Habener, J. F. (1987). Glucagon-like peptide I stimulates insulin gene expression and increases cyclic AMP levels in a rat islet cell line. Proceedings of the National Academy of Sciences, 84(10), 3434-3438.
16. Efird, J., Choi, Y., Davies, S., Mehra, S., Anderson, E., & Katunga, L. (2014). Potential for improved glycemic control with dietary Momordica charantia in patients with insulin resistance and pre-diabetes. International journal of environmental research and public health, 11(2), 2328-2345.
17. Elahi, D., Andersen, D. K., Muller, D. C., Tobin, J. D., Brown, J. C., & Andres, R. (1984). The enteric enhancement of glucose-stimulated insulin release: the role of GIP in aging, obesity, and non-insulin-dependent diabetes mellitus. Diabetes, 33(10), 950-957.
18. Eshghi, S. R. T., Bell, G. J., & Boulé, N. G. (2013). Effects of aerobic exercise with or without metformin on plasma incretins in type 2 diabetes. Canadian journal of diabetes, 37(6), 375-380.
19. Fernandes, N. P., Lagishetty, C. V., Panda, V. S., & Naik, S. R. (2007). An experimental evaluation of the antidiabetic and antilipidemic properties of a standardized Momordica charantia fruit extract. BMC complementary and alternative medicine, 7(1), 29.
20. Gromada, J., Bokvist, K., Ding, W.-G., Holst, J. J., Nielsen, J. H., & Rorsman, P. (1998). Glucagon-like peptide 1 (7-36) amide stimulates exocytosis in human pancreatic β-cells by both proximal and distal regulatory steps in stimulus-secretion coupling. Diabetes, 47 (1), 57-65.
21. Habicht, S. D., Kind, V., Rudloff, S., Borsch, C., Mueller, A. S., Pallauf, J., . . . Krawinkel, M. B. (2011). Quantification of antidiabetic extracts and compounds in bitter gourd varieties. Food chemistry, 126(1), 172-176.
22. Hamasaki, H. (2018). Exercise and glucagon-like peptide-1: Does exercise potentiate the effect of treatment? World journal of diabetes, 9(8), 138.
23. Hansotia, T., Maida, A., Flock, G., Yamada, Y., Tsukiyama, K., Seino, Y., & Drucker, D. J. (2007). Extrapancreatic incretin receptors modulate glucose homeostasis, body weight, and energy expenditure. The Journal of clinical investigation, 117(1), 143-152.
24. Heiskanen, M. A., Motiani, K. K., Mari, A., Saunavaara, V., Eskelinen, J.-J., Virtanen, K. A., . . . Kalliokoski, K. K. (2018.(Exercise training decreases pancreatic fat content and improves beta cell function regardless of baseline glucose tolerance: a randomised controlled trial. Diabetologia, 61(8), 1817-1828.
25. Holst, J. J., & Gromada, J. (2004). Role of incretin hormones in the regulation of insulin secretion in diabetic and nondiabetic humans. American Journal of Physiology-Endocrinology and Metabolism, 287(2), E199-E206.
26. Holst, J. J., Knop, F. K., Vilsbøll, T., Krarup, T., & Madsbad, S. (2011). Loss of incretin effect is a specific, important, and early characteristic of type 2 diabetes. Diabetes Care, 34(Supplement 2), S251-S257.
27. Iwasaki, K., Harada, N., Sasaki, K., Yamane, S., Iida, K., Suzuki, K., . . . Joo, E. (2015). Free fatty acid receptor GPR120 is highly expressed in enteroendocrine K cells of the upper small intestine and has a critical role in GIP secretion after fat ingestion. Endocrinology, 156(3), 837-846.
28. Joseph, B., & Jini, D. (2013). Antidiabetic effects of Momordica charantia (bitter melon) and its medicinal potency. Asian Pacific Journal of Tropical Disease, 3(2), 93-102.
29. Keller, A. C., Ma, J., Kavalier, A., He, K., Brillantes, A.-M. B., & Kennelly, E. J. (2011). Saponins from the traditional medicinal plant Momordica charantia stimulate insulin secretion in vitro. Phytomedicine, 19(1), 32-37.
30. Kelly, K. R., Brooks, L. M., Solomon, T. P., Kashyap, S. R., O'Leary, V. B., & Kirwan, J. P. (2009). The glucose-dependent insulinotropic polypeptide and glucose-stimulated insulin response to exercise training and diet in obesity. American Journal of Physiology-Endocrinology and Metabolism, 296(6), E1269-E1274.
31. Kim, D.-I., Park, M.-J., Choi, J.-H., Lim, S.-K., Choi, H.-J., & Park, S.-H. (2015). Hyperglycemia-induced GLP-1R downregulation causes RPE cell apoptosis. The international journal of biochemistry & cell biology, 59, 41-51.
32. Kim, S.-J., Winter, K., Nian, C., Tsuneoka, M., Koda, Y., & McIntosh, C. H. (2005). GIP stimulation of pancreatic beta-cell survival is dependent upon phosphatidylinositol 3-kinase (PI3-K)/protein kinase B (PKB) signaling, inactivation of the forkhead transcription factor Foxo1 and downregulation of bax expression. Journal of Biological Chemistry, 280(23), 22297-22307.
33. Kjems, L. L., Holst, J. J., Vølund, A., & Madsbad, S. (2003). The influence of GLP-1 on glucose-stimulated insulin secretion: effects on β-cell sensitivity in type 2 and nondiabetic subjects. Diabetes, 52(2), 380-386.
34. Knop, F. K., Vilsboll, T., & Holst, J. J. (2009). Incretin-based therapy of type 2 diabetes mellitus. Current Protein and Peptide Science, 10(1), 46-55.
35. Kreymann, B., Ghatei, M., Williams, G., & Bloom, S. (1987). Glucagon-like peptide-1 7-36: a physiological incretin in man. The Lancet, 330(8571), 1300-1304.
36. Lee, S. S., Yoo, J. H., & So, Y. S. (2015). Effect of the low-versus high-intensity exercise training on endoplasmic reticulum stress and GLP-1 in adolescents with type 2 diabetes mellitus. Journal of physical therapy science, 27(10), 3063-3068.
37. Liu, J., Hu, Y., Zhang, H., Xu, Y., & Wang, G. (2016). Exenatide treatment increases serum irisin levels in patients with obesity and newly diagnosed type 2 diabetes. Journal of Diabetes and its Complications, 30(8), 1555-1559.
38. Mahomoodally, M., Gurib-Fakim, A., & Subratty, A. (2007). Effect of exogenous ATP on Momordica charantia Linn.(Cucurbitaceae) induced inhibition of d-glucose, l-tyrosine and fluid transport across rat everted intestinal sacs in vitro. Journal of ethnopharmacology, 110(2), 257-263.
39. Moher, D., Dulberg, C. S., & Wells, G. A. (1994). Statistical power, sample size, and their reporting in randomized controlled trials. Jama, 272(2), 122-124.
40. Moran-Ramos, S., Tovar, A. R., & Torres, N. (2012). Diet: friend or foe of enteroendocrine cells: how it interacts with enteroendocrine cells. Advances in Nutrition, 3(1), 8-20.
41. Näslund, E., Bogefors, J., Skogar, S., Grybäck, P., Jacobsson, H., Holst, J. J., & Hellström, P. M. (1999). GLP-1 slows solid gastric emptying and inhibits insulin, glucagon, and PYY release in humans. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 277(3), R910-R916.
42. Nejati, R., Attarzadeh Hosseini, S. R., Bijeh, N., & Raouf Saeb, A. (2019). The effects of twelve weeks of combined exercises on GLP-1 and insulin resistance in women with type 2 diabetes. The Journal of Shahid Sadoughi University of Medical Sciences, 27(1), 1187-1201.
43. O’Connor, A. M., Pola, S., Ward, B. M., Fillmore, D., Buchanan, K. D., & Kirwan, J. P. (2006). The gastroenteroinsular response to glucose ingestion during postexercise recovery. American Journal of Physiology-Endocrinology and Metabolism, 290(6), E1155-E1161.
44. Park, S. H., Yoon, J. H., Seo, D. Y., Kim, T. N., Ko, J. R., & Han, J. (2019). Resistance Exercise Training Attenuates the Loss of Endogenous GLP-1 Receptor in the Hypothalamus of Type 2 Diabetic Rats. International journal of environmental research and public health, 16(5), 830.
45. Pedersen, B. K. (2009). The diseasome of physical inactivity–and the role of myokines in muscle–fat cross talk. The Journal of physiology, 587(23), 5559-5568.
46. Peter, E. L., Kasali, F. M., Deyno, S., Mtewa, A., Nagendrappa, P. B., Tolo, C. U., . . . Sesaazi, D. (2018). Momordica charantia L. lowers elevated glycaemia in Type 2 Diabetes Mellitus Patients: Systematic review and Meta-analysis. Journal of ethnopharmacology, 1;231:311-324.
47. Reimann, F., Tolhurst, G., & Gribble, F. M. (2012). G-protein-coupled receptors in intestinal chemosensation. Cell metabolism, 15(4), 421-431.
48. Salera, M., Giacomoni, P., Pironi, L., Cornia, G., Capelli, M., Marinin, A., . . . Barbara, L. (1982). Gastric inhibitory polypeptide release after oral glucose: relationship to glucose intolerance, diabetes mellitus, and obesity. The Journal of Clinical Endocrinology & Metabolism, 55(2), 329-336.
49. Shaabani, M., Abolfathi, F., & Alizadeh, A. A. (2016). Serum Glucagon-Like Peptide-1 Changes in Women with Type 2 Diabetes Following a Four Weeks Aerobic Exercise. Iranian Journal of Diabetes and Obesity, 8(2), 61-66.
50. Shao, W., Wang, D., Chiang, Y.-T., Ip, W., Zhu, L., Xu, F., . . . Zhang, H. (2013). The Wnt signaling pathway effector TCF7L2 controls gut and brain proglucagon gene expression and glucose homeostasis. Diabetes, 62(3), 789-800.
51. Solomon, T. P., Haus, J. M., Kelly, K. R., Rocco, M., Kashyap, S. R., & Kirwan, J. P. (2010). Improved pancreatic beta-cell function in type 2 diabetics following lifestyle-induced weight loss is related to glucose-dependent insulinotropic polypeptide. Diabetes Care, 33(7): 1561–1566.
52. Tahrani, A. A., Bailey, C. J., Del Prato, S., & Barnett, A. H. (2011). Management of type 2 diabetes: new and future developments in treatment. The Lancet, 378(9786), 182-197.
53. Todd, J., & Bloom, S. (2007). Incretins and other peptides in the treatment of diabetes. Diabetic medicine, 24(3), 223-232.
54. Tsukiyama, K., Yamada, Y., Yamada, C., Harada, N., Kawasaki, Y., Ogura, M., . . . Sato, M. (2006). Gastric inhibitory polypeptide as an endogenous factor promoting new bone formation after food ingestion. Molecular Endocrinology, 20(7), 1644-1651.
55. Uebanso, T., Arai, H., Taketani, Y., Fukaya, M., Yamamoto, H., Mizuno, A., . . . Takeda, E. (2007). Extracts of Momordica charantia suppress postprandial hyperglycemia in rats. Journal of nutritional science and vitaminology, 53(6), 482-488.
56. Ueda, S.-y., Miyamoto, T., Nakahara, H., Shishido, T., Usui, T., Katsura, Y., . . . Fujimoto, S. (2013). Effects of exercise training on gut hormone levels after a single bout of exercise in middle-aged Japanese women. Springerplus, 2(1), 83.
57. Unwin, N., Whiting, D., Gan, D., Jacqmain, O., & Ghyoot, G. (2009). IDF diabetes atlas: International Diabetes Federation.
58. Wadkar, K., Magdum, C., Patil, S., & Naikwade, N. (2008). Anti-diabetic potential and Indian medicinal plants. Journal of herbal medicine and toxicology, 2(1), 45-50.
59. Wang, Z. Q., Zhang, X. H., Yu, Y., Poulev, A., Ribnicky, D., Floyd, Z. E., & Cefalu, W. T. (2011). Bioactives from bitter melon enhance insulin signaling and modulate acyl carnitine content in skeletal muscle in high-fat diet-fed mice. The Journal of nutritional biochemistry, 22(11), 1064-1073.
60. Zhang, Y., Li, X., Li, J., Zhang, Q., Chen, X., Liu, X., . . . Hu, Y. (2016). The anti-hyperglycemic efficacy of a lipid-lowering drug Daming capsule and the underlying signaling mechanisms in a rat model of diabetes mellitus. Scientific reports, 6, 34284.
61. Zimmet, P., Alberti, K., & Shaw, J. (2001). Global and societal implications of the diabetes epidemic. Nature, 414(6865), 782.