Research Article

Exercise preserves pancreatic β-cell mass and function in obese OLETF rats

Jiawei Zhao, Zhihong Yang, Min He, Qinghua Wang and Renming Hu*

Published: 19 June, 2018 | Volume 2 - Issue 1 | Pages: 022-029

Although exercise has been proposed to be beneficial to type 2 diabetes, its effects on β-cell function and mass remain unclear. In the present study, the effects of long-term swimming training on the function and mass of β-cells in diabetic OLETF rats were examined. At 44 weeks of age after developing diabetes, the OLETF rats were divided into two groups: a control group and an exercise group. The exercise group had a daily swimming for 12 weeks. While not found with the control rats, in the obese OLETF rats, the exercise reduced the weight gain which was associated with improved glucose tolerance and elevated circulating insulin levels as determined by the oral glucose tolerance test and insulin ELISA. The exercise improved plasma total cholesterol and triglyceride levels, and also significantly increased the islet β-cell mass and pancreatic insulin content associated with decreased β-cell apoptosis and elevated activation of the serine/threonine kinase, Akt. The present studies suggest that exercise improves diabetes symptoms via enhancement of the β-cell mass and function through decreasing glucolipotoxicity and reducing β-cell apoptosis by activating Akt in obese OLETF rats.

Read Full Article HTML DOI: 10.29328/journal.acem.1001007 Cite this Article Read Full Article PDF


Exercise; Diabetes; Islets; β-cell mass


  1. Manson JE, Rimm EB, Stampfer MJ, Colditz GA, Willett WC, et al. Physical activity and incidence of non-insulin-dependent diabetes mellitus in women. Lancet. 1991; 338: 774-778. Ref.: https://tinyurl.com/y8dz94fg
  2. Pan XR, Li GW, Hu YH, Wang JX, Yang WY, et al. Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance. The Da Qing IGT and Diabetes Study. Diabetes Care. 1997; 20:537- 544. Ref.: https://tinyurl.com/y9657hcr
  3. Pold R, Jensen LS, Jessen N, Buhl ES, Schmitz O, et al. Long-term AICAR administration and exercise prevents diabetes in ZDF rats. Diabetes. 2005; 54: 928-934. Ref.: https://tinyurl.com/yad8kvje
  4. Mizuno A, Noma Y, Kuwajima M, Murakami T, Zhu M, et al. Changes in islet capillary angioarchitecture coincide with impaired B-cell function but not with insulin resistance in male Otsuka-Long-Evans-Tokushima fatty rats: dimorphism of the diabetic phenotype at an advanced age. Metabolism. 1999; 48:477- 483. Ref.: https://tinyurl.com/y9ldt4of
  5. Tomoyuki Nishimoto, Yuichiro Amano, Ryuichi Tozawa, Eiichiro Ishikawa, Yoshimi Imura, et al. Lipid-lowering properties of TAK-475, a squalene synthase inhibitor, in vivo and in vitro. Br J Pharmacol. 2003; 139: 911- 918. Ref.: https://tinyurl.com/yd7w9u2m
  6. Wang Q, Brubaker PL. Glucagon-like peptide-1 treatment delays the onset of diabetes in 8 week-old db/db mice. Diabetologia. 2002; 45: 1263-1273. Ref.: https://tinyurl.com/ydyxthup
  7. Scaglia L, Cahill CJ, Finegood DT, Bonner-Weir S. Apoptosis participates in the remodeling of the endocrine pancreas in the neonatal rat. Endocrinology. 1997; 138: 1736-1741. Ref.: https://tinyurl.com/ybpyqusq
  8. Beck-Nielsen H, Pedersen O, Lindskov HO. Normalization of the insulin sensitivity and the cellular insulin binding during treatment of obese diabetics for one year. Acta Endocrinol (Copenh). 1979; 90: 103-112. Ref.: https://tinyurl.com/y74zrm7u
  9. Freidenberg GR, Reichart D, Olefsky JM, Henry RR. Reversibility of defective adipocyte insulin receptor kinase activity in non-insulin-dependent diabetes mellitus. Effect of weight loss. J Clin Invest. 1988; 82: 1398-1406. Ref.: https://tinyurl.com/yb8kyl4z
  10. Manson JE, Nathan DM, Krolewski AS, Stampfer MJ, Willett WC, et al. A prospective study of exercise and incidence of diabetes among US male physicians. JAMA. 1992; 268: 63-67. Ref.: https://tinyurl.com/y9ztz3as
  11. Crawford DA, Jeffery RW, French SA. Television viewing, physical inactivity and obesity. Int J Obes Relat Metab Disord. 1999; 23: 437-440. Ref.: https://tinyurl.com/yddx4l6q
  12. Martínez-González MA, Martínez JA, Hu FB, Gibney MJ, Kearney J, et al. Physical inactivity, sedentary lifestyle and obesity in the European Union. Int J Obes Relat Metab Disord. 1999; 23: 1192-1201. Ref.: https://tinyurl.com/ybwsdbqq
  13. Youngren JF, Keen S, Kulp JL, Tanner CJ, Houmard JA, et al. Enhanced muscle insulin receptor autophosphorylation with short-term aerobic exercise training. Am J Physiol Endocrinol Metab. 2001; 280: 528-533. Ref.: https://tinyurl.com/ydf5dmb4
  14. Holten MK, Zacho M, Gaster M, Juel C, Wojtaszewski JF, et al. Strength training increases insulin-mediated glucose uptake, GLUT4 content, and insulin signaling in skeletal muscle in patients with type 2 diabetes. Diabetes. 2004; 53: 294-305. Ref.: https://tinyurl.com/y9srdo59
  15. Saltin B, Helge JW. Metabolic capacity of skeletal muscles and health. Ugeskr Laeger. 2000; 162: 2159-2164. Ref.: https://tinyurl.com/y9hrawkw
  16. Ivy JL, Zderic TW, Fogt DL. Prevention and treatment of non-insulin-dependent diabetes mellitus. Exerc Sport Sci Rev. 1999; 27: 1-35. Ref.: https://tinyurl.com/ybnh39mu
  17. Donath MY, Ehses JA, Maedler K, Schumann DM, Ellingsgaard H, et al. Mechanisms of beta-cell death in type 2 diabetes. Diabetes. 2005; 2: 108-113. Ref.: https://tinyurl.com/y7jdlfgo
  18. Bonner-Weir S. Life and death of the pancreatic beta cells. Trends Endocrinol Metab. 2000; 11: 375-378. Ref.: https://tinyurl.com/ybfhnrtp
  19. Pick A, Clark J, Kubstrup C, Levisetti M, Pugh W, et al. Role of apoptosis in failure of beta-cell mass compensation for insulin resistance and beta-cell defects in the male Zucker diabetic fatty rat. Diabetes. 1998; 47: 358- 364. Ref.: https://tinyurl.com/y9w6edoh
  20. Butler AE, Janson J, Bonner-Weir S, Ritzel R, Rizza RA , et al. Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. Diabetes. 2003; 52: 102-110. Ref.: https://tinyurl.com/y75wps4e
  21. El-Assaad W, Buteau J, Peyot ML, Nolan C, Roduit R, et al. Saturated fatty acids synergize with elevated glucose to cause pancreatic beta-cell death. Endocrinology. 2003; 144: 4154-4163. Ref.: https://tinyurl.com/y7cyyt4t
  22. Dickson LM, Rhodes CJ. Pancreatic beta-cell growth and survival in the onset of type 2 diabetes: a role for protein kinase B in the Akt? Am J Physiol Endocrinol Metab. 2004; 287: 192-198. Ref.: https://tinyurl.com/y7m4gn56
  23. Qi J, Yang B, Ren C, Fu J, Zhang J. Swimming Exercise Alleviated Insulin Resistance by Regulating Tripartite Motif Family Protein 72 Expression and AKT Signal Pathway in Sprague-Dawley Rats Fed with High-Fat Diet. J Diabetes Res. 2016; Ref.: https://tinyurl.com/ybs47p62
  24. White MF. IRS proteins and the common path to diabetes. Am J Physiol Endocrinol Metab. 2002; 283: 413-422. Ref.: https://tinyurl.com/y94ugynx
  25. Wang Q, Li L, Xu E, Wong V, Rhodes C, et al. Glucagon-like peptide-1 regulates proliferation and apoptosis via activation of protein kinase B in pancreatic INS-1 beta cells. Diabetologia. 2004; 47: 478-487. Ref.: https://tinyurl.com/ybefeuxv
  26. Wrede CE, Dickson LM, Lingohr MK, Briaud I, Rhodes CJ. Protein kinase B/Akt prevents fatty acid-induced apoptosis in pancreatic beta-cells (INS-1). J Biol Chem. 2002; 277: 49676-49684. Ref.: https://tinyurl.com/ydbaaach
  27. Elghazi L, Balcazar N, Bernal-Mizrachi E. Emerging role of protein kinase B/Akt signaling in pancreatic beta-cell mass and function. Int J Biochem Cell Biol. 2006; 38:157-163. Ref.: https://tinyurl.com/yb84boxp
  28. Zhao J, Zhang N, He M, Yang Z, Tong W, et al. Increased β-cell apoptosis and impaired insulin signaling pathway contributes to the onset of diabetes in OLETF rats. Cell Physiol Biochem. 2008; 21: 445-454. Ref.: https://tinyurl.com/yb9bbj9d


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