DOI QR코드

DOI QR Code

Both sitagliptin analogue & pioglitazone preserve the β-cell proportion in the islets with different mechanism in non-obese and obese diabetic mice

  • Yeom, Jin-A ;
  • Kim, Eun-Sook ;
  • Park, Heon-Seok ;
  • Ham, Dong-Sik ;
  • Sun, Cheng-Lin ;
  • Kim, Ji-Won ;
  • Cho, Jae-Hyoung ;
  • Yoon, Kun-Ho
  • Received : 2011.06.30
  • Accepted : 2011.08.16
  • Published : 2011.11.30

Abstract

In this study, the effects of sitagliptin analogue (SITA) or pioglitazone (PIO) treatment on glucose homeostasis and ${\beta}$-cell dynamics in animal models of type 2 diabetes-Akita and db/db mice were evaluated. After 4-6 weeks of treatment, both SITA and PIO were shown to lower non-fasting glucose levels and reduced glycemic excursion in the intraperitoneal glucose tolerance test. In addition, both drugs preserved normal islet structure and the proportion of ${\beta}$-cells in the islets. Compared to the controls, SITA treatment induced a higher ${\beta}$-cell proliferation rate in Akita mice and a lower rate of apoptosis in db/db mice, whereas PIO treatment induced a lower rate of apoptosis in db/db mice and reduced proliferation rates in Akita mice. In conclusion, both SITA and PIO appear to exert some beneficial effects on the islet structure in addition to glycemic control via different mechanisms that involve ${\beta}$-cell dynamics in Akita and db/db mice.

Keywords

Akita mice;db/db mice;Pioglitazone;Sitagliptin analogue;Type 2 diabetes

References

  1. Kahn, S. E., Prigeon, R. L., McCulloch, D. K., Boyko, E. J., Bergman, R. N., Schwartz, M. W., Neifing, J. L., Ward, W. K., Beard, J. C. and Palmer, J. P. (1993) Quantification of the relationship between insulin sensitivity and beta-cell function in human subjects. Evidence for a hyperbolic function. Diabetes 42, 1663-1672. https://doi.org/10.2337/diabetes.42.11.1663
  2. Bergman, R. N., Phillips, L. S. and Cobelli, C. (1981) Physiologic evaluation of factors controlling glucose tolerance in man: measurement of insulin sensitivity and beta-cell glucose sensitivity from the response to intravenous glucose. J. Clin. Invest. 68, 1456-1467. https://doi.org/10.1172/JCI110398
  3. Butler, A. E., Janson, J., Bonner-Weir, S., Ritzel, R., Rizza, R. A. and Butler, P. C. (2003) Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. Diabetes 52, 102-110. https://doi.org/10.2337/diabetes.52.1.102
  4. UK Prospective Diabetes Study (UKPDS) Group. (1998) Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 352, 837-853. https://doi.org/10.1016/S0140-6736(98)07019-6
  5. Montanya, E., Nacher, V., Biarns, M. and Soler, J. (2000) Linear correlation between beta-cell mass and body weight throughout the lifespan in Lewis rats: role of beta-cell hyperplasia and hypertrophy. Diabetes 49, 1341-1346. https://doi.org/10.2337/diabetes.49.8.1341
  6. Pospisilik, J. A., Martin, J., Doty, T., Ehses, J. A., Pamir, N., Lynn, F. C., Piteau, S., Demuth, H., McIntosh, C. H. and Pederson, R. A. (2003) Dipeptidyl peptidase IV inhibitor treatment stimulates beta-cell survival and islet neogenesis in streptozotocin-induced diabetic rats. Diabetes 52, 741-750. https://doi.org/10.2337/diabetes.52.3.741
  7. Mu, J., Woods, J., Zhou, Y., Roy, R. S., Li, Z., Zycband, E., Feng, Y., Zhu, L., Li, C., Howard, A. D., Moller, D. E., Thornberry, N. A. and Zhang, B. (2006) Chronic inhibition of dipeptidyl peptidase-4 with a sitagliptin analog preserves pancreatic beta-cell mass and function in a rodent model of type 2 diabetes. Diabetes 55, 1695-1704. https://doi.org/10.2337/db05-1602
  8. Drucker, D. J. (2003) Glucagon-like peptides: regulators of cell proliferation, differentiation, and apoptosis. Mol. Endocrinol. 17, 161-171. https://doi.org/10.1210/me.2002-0306
  9. Nonaka, K., Kakikawa, T., Sato, A., Okuyama, K., Fujimoto, G., Kato, N., Suzuki, H., Hirayama, Y., Ahmed, T., Davies, M. J. and Stein, P. (2008) Efficacy and safety of sitagliptin monotherapy in Japanese patients with type 2 diabetes. Diabetes Res. Clin. Pract. 79, 291-298. https://doi.org/10.1016/j.diabres.2007.08.021
  10. Raz, I., Hanefeld, M., Xu, L., Caria, C., Williams-Herman, D. and Khatami, H. (2006) Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy in patients with type 2 diabetes mellitus. Diabetologia 49, 2564-2571. https://doi.org/10.1007/s00125-006-0416-z
  11. Higa, M., Zhou, Y. T., Ravazzola, M., Baetens, D., Orci, L. and Unger, R. H. (1999) Troglitazone prevents mitochondrial alterations, beta cell destruction, and diabetes in obese prediabetic rats. Proc. Natl. Acad. Sci. U.S.A. 96, 11513-11518. https://doi.org/10.1073/pnas.96.20.11513
  12. Finegood, D. T., McArthur, M. D., Kojwang, D., Thomas, M. J., Topp, B. G., Leonard, T. and Buckingham, R. E. (2001) Betacell mass dynamics in Zucker diabetic fatty rats. Rosiglitazone prevents the rise in net cell death. Diabetes 50, 1021-1029. https://doi.org/10.2337/diabetes.50.5.1021
  13. Campbell, I. W. and Mariz, S. (2007) Beta-cell preservation with thiazolidinediones. Diabetes Res. Clin. Pract. 76, 163-176. https://doi.org/10.1016/j.diabres.2006.08.015
  14. Chen, H., Charlat, O., Tartaglia, L. A., Woolf, E. A., Weng, X., Ellis, S. J., Lakey, N. D., Culpepper, J., Moore, K. J., Breitbart, R. E., Duyk, G. M., Tepper, R. I. and Morgenstern, J. P. (1996) Evidence that the diabetes gene encodes the leptin receptor: identification of a mutation in the leptin receptor gene in db/db mice. Cell 84, 491-495. https://doi.org/10.1016/S0092-8674(00)81294-5
  15. Yoshioka, M., Kayo, T., Ikeda, T. and Koizumi, A. (1997) A novel locus, Mody4, distal to D7Mit189 on chromosome 7 determines early-onset NIDDM in nonobese C57BL/6 (Akita) mutant mice. Diabetes 46, 887-894. https://doi.org/10.2337/diabetes.46.5.887
  16. Drucker, D. J. and Nauck, M. A. (2006) The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet 368, 1696-1705. https://doi.org/10.1016/S0140-6736(06)69705-5
  17. Matveyenko, A. V., Dry, S., Cox, H. I., Moshtaghian, A., Gurlo, T., Galasso, R., Butler, A. E. and Butler, P. C. (2009) Beneficial endocrine but adverse exocrine effects of sitagliptin in the human islet amyloid polypeptide transgenic rat model of type 2 diabetes: interactions with metformin. Diabetes 58, 1604-1615. https://doi.org/10.2337/db09-0058
  18. Mu, J., Petrov, A., Eiermann, G. J., Woods, J., Zhou, Y., Li, Z., Zycband, E., Feng, Y., Zhu, L., Roy, R. S., Howard, A. D., Li, C., Thornberry, N. A. and Zhang, B. (2009) Inhibition of DPP-4 with sitagliptin improves glycemic control and restores islet cell mass and function in a rodent model of type 2 diabetes. Eur. J. Pharmacol. 623, 148-154. https://doi.org/10.1016/j.ejphar.2009.09.027
  19. Yki-Jrvinen, H. (2004) Thiazolidinediones. N. Engl. J. Med. 351, 1106-1118. https://doi.org/10.1056/NEJMra041001
  20. Robertson, R. P., Harmon, J., Tran, P. O., Tanaka, Y. and Takahashi, H. (2003) Glucose toxicity in beta-cells: type 2 diabetes, good radicals gone bad, and the glutathione connection. Diabetes 52, 581-587. https://doi.org/10.2337/diabetes.52.3.581
  21. Saitoh, Y., Chun-ping, C., Noma, K., Ueno, H., Mizuta, M. and Nakazato, M. (2008) Pioglitazone attenuates fatty acid-induced oxidative stress and apoptosis in pancreatic beta-cells. Diabetes Obes. Metab. 10, 564-573. https://doi.org/10.1111/j.1463-1326.2007.00749.x
  22. Izumi, T., Yokota-Hashimoto, H., Zhao, S., Wang, J., Halban, P. A. and Takeuchi, T. (2003) Dominant negative pathogenesis by mutant proinsulin in the Akita diabetic mouse. Diabetes 52, 409-416. https://doi.org/10.2337/diabetes.52.2.409
  23. Oyadomari, S., Koizumi, A., Takeda, K., Gotoh, T., Akira, S., Araki, E. and Mori, M. (2002) Targeted disruption of the Chop gene delays endoplasmic reticulum stress-mediated diabetes. J. Clin. Invest. 109, 525-532. https://doi.org/10.1172/JCI0214550
  24. O'Brien, B. A., Huang, Y., Geng, X., Dutz, J. P. and Finegood, D. T. (2002) Phagocytosis of apoptotic cells by macrophages from NOD mice is reduced. Diabetes 51, 2481-2488. https://doi.org/10.2337/diabetes.51.8.2481
  25. Xu, G., Stoffers, D. A., Habener, J. F. and Bonner-Weir, S. (1999) Exendin-4 stimulates both beta-cell replication and neogenesis, resulting in increased beta-cell mass and improved glucose tolerance in diabetic rats. Diabetes 48, 2270-2276. https://doi.org/10.2337/diabetes.48.12.2270
  26. Xu, G., Kaneto, H., Lopez-Avalos, M. D., Weir, G. C. and Bonner-Weir, S. (2006) GLP-1/exendin-4 facilitates beta-cell neogenesis in rat and human pancreatic ducts. Diabetes Res. Clin. Pract. 73, 107-110. https://doi.org/10.1016/j.diabres.2005.11.007
  27. Kim, S., Winter, K., Nian, C., Tsuneoka, M., Koda, Y. and McIntosh, C. H. (2005) Glucose-dependent insulinotropic polypeptide (GIP) stimulation of pancreatic beta-cell survival is dependent upon phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB) signaling, inactivation of the forkhead transcription factor Foxo1, and down-regulation of bax expression. J. Biol. Chem. 280, 22297-22307. https://doi.org/10.1074/jbc.M500540200
  28. Kim, S., Nian, C., Widenmaier, S. and McIntosh, C. H. (2008) Glucose-dependent insulinotropic polypeptide-mediated up-regulation of beta-cell antiapoptotic Bcl-2 gene expression is coordinated by cyclic AMP (cAMP) response element binding protein (CREB) and cAMP-responsive CREB coactivator 2. Mol. Cell. Biol. 28, 1644-1656. https://doi.org/10.1128/MCB.00325-07
  29. Doyle, M. E. and Egan, J. M. (2007) Mechanisms of action of glucagon-like peptide 1 in the pancreas. Pharmacol. Ther. 113, 546-593. https://doi.org/10.1016/j.pharmthera.2006.11.007
  30. Friedrichsen, B. N., Neubauer, N., Lee, Y. C., Gram, V. K., Blume, N., Petersen, J. S., Nielsen, J. H. and Mldrup, A. (2006) Stimulation of pancreatic beta-cell replication by incretins involves transcriptional induction of cyclin D1 via multiple signalling pathways. J. Endocrinol. 188, 481-492. https://doi.org/10.1677/joe.1.06160
  31. Han, S. J., Kang, E. S., Hur, K. Y., Kim, H. J., Kim, S. H., Yun, C., Choi, S. E., Ahn, C. W., Cha, B. S., Kang, Y. and Lee, H. C. (2008) Rosiglitazone inhibits early stage of glucolipotoxicity-induced beta-cell apoptosis. Horm. Res. 70, 165-173. https://doi.org/10.1159/000137662
  32. Rhodes, C. J. (2005) Type 2 diabetes-a matter of beta-cell life and death? Science 307, 380-384. https://doi.org/10.1126/science.1104345
  33. Bonner-Weir, S., Deery, D., Leahy, J. L. and Weir, G. C. (1989) Compensatory growth of pancreatic beta-cells in adult rats after short-term glucose infusion. Diabetes 38, 49-53. https://doi.org/10.2337/diabetes.38.1.49
  34. Parsons, J. A., Brelje, T. C. and Sorenson, R. L. (1992) Adaptation of islets of Langerhans to pregnancy: increased islet cell proliferation and insulin secretion correlates with the onset of placental lactogen secretion. Endocrinology 130, 1459-1466. https://doi.org/10.1210/en.130.3.1459
  35. Kawasaki, F., Matsuda, M., Kanda, Y., Inoue, H. and Kaku, K. (2005) Structural and functional analysis of pancreatic islets preserved by pioglitazone in db/db mice. Am. J. Physiol. Endocrinol. Metab. 288, E510-518. https://doi.org/10.1152/ajpendo.00128.2004
  36. Lamont, B. J. and Drucker, D. J. (2008) Differential antidiabetic efficacy of incretin agonists versus DPP-4 inhibition in high fat fed mice. Diabetes 57, 190-198. https://doi.org/10.2337/db07-1202

Cited by

  1. Trigonelline attenuates hepatic complications and molecular alterations in high-fat high-fructose diet-induced insulin resistance in rats vol.95, pp.4, 2017, https://doi.org/10.1139/cjpp-2016-0269
  2. Cardioprotective effect of concomitant administration of trigonelline and sitagliptin on cardiac biomarkers, lipid levels, electrocardiographic and heamodynamic modulation on cardiomyopathy in diabetic Wistar rats vol.4, pp.4, 2014, https://doi.org/10.1016/j.biomag.2014.07.009
  3. Novel AGLP-1 albumin fusion protein as a long-lasting agent for type 2 diabetes vol.46, pp.12, 2013, https://doi.org/10.5483/BMBRep.2013.46.12.106
  4. Antihyperglycemic activity of trigonelline and sitagliptin in nicotinamide-streptozotocin induced diabetes in Wistar rats vol.3, pp.3, 2013, https://doi.org/10.1016/j.biomag.2013.05.006
  5. Hope and fear for new classes of type 2 diabetes drugs: is there preclinical evidence that incretin-based therapies alter pancreatic morphology? vol.221, pp.1, 2014, https://doi.org/10.1530/JOE-13-0577
  6. Renoprotective Effects of the Dipeptidyl Peptidase-4 Inhibitor Sitagliptin: A Review in Type 2 Diabetes vol.2017, 2017, https://doi.org/10.1155/2017/5164292
  7. Effect of metformin and pioglitazone on β-catenin and biochemical markers in sitagliptin-induced pancreatitis in diabetic rats vol.35, pp.3, 2015, https://doi.org/10.1007/s13410-014-0278-8
  8. Sitagliptin prevents aggravation of endocrine and exocrine pancreatic damage in the Zucker Diabetic Fatty rat - focus on amelioration of metabolic profile and tissue cytoprotective properties vol.6, pp.1, 2014, https://doi.org/10.1186/1758-5996-6-42