Table of Contents Author Guidelines Submit a Manuscript
Mediators of Inflammation
Volume 2016, Article ID 3094642, 11 pages
http://dx.doi.org/10.1155/2016/3094642
Review Article

Anti-Inflammatory Effects of GLP-1-Based Therapies beyond Glucose Control

1Lee Gil Ya Cancer and Diabetes Institute, Gachon University, 7-45 Songdo-dong, Yeonsu-ku, Incheon 406-840, Republic of Korea
2College of Pharmacy and Gachon Institute of Pharmaceutical Science, Gachon University, 7-45 Songdo-dong, Yeonsu-ku, Incheon 406-840, Republic of Korea
3Gachon Medical Research Institute, Gil Hospital, Incheon 405-760, Republic of Korea

Received 5 February 2016; Revised 2 March 2016; Accepted 3 March 2016

Academic Editor: Joilson O. Martins

Copyright © 2016 Young-Sun Lee and Hee-Sook Jun. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. C. Ørskov, L. Rabenhøj, A. Wettergren, H. Kofod, and J. J. Holst, “Tissue and plasma concentrations of amidated and glycine-extended glucagon-like peptide I in humans,” Diabetes, vol. 43, no. 4, pp. 535–539, 1994. View at Publisher · View at Google Scholar · View at Scopus
  2. L. L. Kjems, J. J. Holst, A. Vølund, and S. Madsbad, “The influence of GLP-1 on glucose-stimulated insulin secretion: effects on β-cell sensitivity in type 2 and nondiabetic subjects,” Diabetes, vol. 52, no. 2, pp. 380–386, 2003. View at Publisher · View at Google Scholar · View at Scopus
  3. R. Mentlein, B. Gallwitz, and W. E. Schmidt, “Dipeptidyl-peptidase IV hydrolyses gastric inhibitory polypeptide, glucagon-like peptide-1(7-36)amide, peptide histidine methionine and is responsible for their degradation in human serum,” European Journal of Biochemistry, vol. 214, no. 3, pp. 829–835, 1993. View at Publisher · View at Google Scholar · View at Scopus
  4. Y.-S. Lee and H.-S. Jun, “Anti-diabetic actions of glucagon-like peptide-1 on pancreatic beta-cells,” Metabolism: Clinical and Experimental, vol. 63, no. 1, pp. 9–19, 2014. View at Publisher · View at Google Scholar · View at Scopus
  5. M. Karaca, C. Magnan, and C. Kargar, “Functional pancreatic beta-cell mass: involvement in type 2 diabetes and therapeutic intervention,” Diabetes & Metabolism, vol. 35, no. 2, pp. 77–84, 2009. View at Publisher · View at Google Scholar · View at Scopus
  6. D. J. Drucker, “The biology of incretin hormones,” Cell Metabolism, vol. 3, no. 3, pp. 153–165, 2006. View at Publisher · View at Google Scholar · View at Scopus
  7. A. J. Tremblay, B. Lamarche, C. F. Deacon, S. J. Weisnagel, and P. Couture, “Effects of sitagliptin therapy on markers of low-grade inflammation and cell adhesion molecules in patients with type 2 diabetes,” Metabolism: Clinical and Experimental, vol. 63, no. 9, pp. 1141–1148, 2014. View at Publisher · View at Google Scholar · View at Scopus
  8. M. L. Balestrieri, M. R. Rizzo, M. Barbieri et al., “Sirtuin 6 expression and inflammatory activity in diabetic atherosclerotic plaques: effects of incretin treatment,” Diabetes, vol. 64, no. 4, pp. 1395–1406, 2015. View at Publisher · View at Google Scholar
  9. A. Varanasi, P. Patel, A. Makdissi, S. Dhindsa, A. Chaudhuri, and P. Dandona, “Clinical use of liraglutide in type 2 diabetes and its effects on cardiovascular risk factors,” Endocrine Practice, vol. 18, no. 2, pp. 140–145, 2012. View at Publisher · View at Google Scholar · View at Scopus
  10. A. J. Garber, “Long-acting glucagon-like peptide 1 receptor agonists: a review of their efficacy and tolerability,” Diabetes Care, vol. 34, supplement 2, pp. S279–S284, 2011. View at Publisher · View at Google Scholar · View at Scopus
  11. M. Nauck, “Incretin therapies: highlighting common features and differences in the modes of action of glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors,” Diabetes, Obesity & Metabolism, vol. 18, no. 3, pp. 203–216, 2016. View at Publisher · View at Google Scholar
  12. M. Arakawa, T. Mita, K. Azuma et al., “Inhibition of monocyte adhesion to endothelial cells and attenuation of atherosclerotic lesion by a glucagon-like peptide-1 receptor agonist, exendin-4,” Diabetes, vol. 59, no. 4, pp. 1030–1037, 2010. View at Publisher · View at Google Scholar · View at Scopus
  13. B. Thorens, “Expression cloning of the pancreatic β cell receptor for the gluco- incretin hormone glucagon-like peptide 1,” Proceedings of the National Academy of Sciences of the United States of America, vol. 89, no. 18, pp. 8641–8645, 1992. View at Publisher · View at Google Scholar · View at Scopus
  14. H. Fujita, T. Morii, H. Fujishima et al., “The protective roles of GLP-1R signaling in diabetic nephropathy: possible mechanism and therapeutic potential,” Kidney International, vol. 85, no. 3, pp. 579–589, 2014. View at Publisher · View at Google Scholar · View at Scopus
  15. M. Romaní-Pérez, V. Outeiriño-Iglesias, M. Gil-Lozano, L. C. González-Matías, F. Mallo, and E. Vigo, “Pulmonary GLP-1 receptor increases at birth and exogenous GLP-1 receptor agonists augmented surfactant-protein levels in litters from normal and nitrofen-treated pregnant rats,” Endocrinology, vol. 154, no. 3, pp. 1144–1155, 2013. View at Publisher · View at Google Scholar · View at Scopus
  16. R. Goke, P. J. Larsen, J. D. Mikkelsen, and S. P. Sheikh, “Distribution of GLP-1 binding sites in the rat brain: evidence that exendin-4 is a ligand of brain GLP-1 binding sites,” The European Journal of Neuroscience, vol. 7, no. 11, pp. 2294–2300, 1995. View at Publisher · View at Google Scholar · View at Scopus
  17. T. Iwai, S. Ito, K. Tanimitsu, S. Udagawa, and J.-I. Oka, “Glucagon-like peptide-1 inhibits LPS-induced IL-1β production in cultured rat astrocytes,” Neuroscience Research, vol. 55, no. 4, pp. 352–360, 2006. View at Publisher · View at Google Scholar · View at Scopus
  18. Y.-S. Lee, M.-S. Park, J.-S. Choung et al., “Glucagon-like peptide-1 inhibits adipose tissue macrophage infiltration and inflammation in an obese mouse model of diabetes,” Diabetologia, vol. 55, no. 9, pp. 2456–2468, 2012. View at Publisher · View at Google Scholar · View at Scopus
  19. A. D. Dobrian, Q. Ma, J. W. Lindsay et al., “Dipeptidyl peptidase IV inhibitor sitagliptin reduces local inflammation in adipose tissue and in pancreatic islets of obese mice,” The American Journal of Physiology—Endocrinology and Metabolism, vol. 300, no. 2, pp. E410–E421, 2011. View at Publisher · View at Google Scholar · View at Scopus
  20. C. Cabou and R. Burcelin, “GLP-1, the gut-brain, and brain-periphery axes,” Review of Diabetic Studies, vol. 8, no. 3, pp. 418–431, 2011. View at Publisher · View at Google Scholar · View at Scopus
  21. X.-C. Wang, A. M. Gusdon, H. Liu, and S. Qu, “Effects of glucagon-like peptide-1 receptor agonists on non-alcoholic fatty liver disease and inflammation,” World Journal of Gastroenterology, vol. 20, no. 40, pp. 14821–14830, 2014. View at Publisher · View at Google Scholar · View at Scopus
  22. M. Blandino-Rosano, G. Perez-Arana, J. M. Mellado-Gil, C. Segundo, and M. Aguilar-Diosdado, “Anti-proliferative effect of pro-inflammatory cytokines in cultured β cells is associated with extracellular signal-regulated kinase 1/2 pathway inhibition: protective role of glucagon-like peptide -1,” Journal of Molecular Endocrinology, vol. 41, no. 1-2, pp. 35–44, 2008. View at Publisher · View at Google Scholar · View at Scopus
  23. H. Liu, A. E. Dear, L. B. Knudsen, and R. W. Simpson, “A long-acting glucagon-like peptide-1 analogue attenuates induction of plasminogen activator inhibitor type-1 and vascular adhesion molecules,” The Journal of Endocrinology, vol. 201, no. 1, pp. 59–66, 2009. View at Publisher · View at Google Scholar · View at Scopus
  24. V. Parthsarathy and C. Hölscher, “The type 2 diabetes drug liraglutide reduces chronic inflammation induced by irradiation in the mouse brain,” European Journal of Pharmacology, vol. 700, no. 1–3, pp. 42–50, 2013. View at Publisher · View at Google Scholar · View at Scopus
  25. C. Marques, C. Mega, A. Gonçalves et al., “Sitagliptin prevents inflammation and apoptotic cell death in the kidney of type 2 diabetic animals,” Mediators of Inflammation, vol. 2014, Article ID 538737, 15 pages, 2014. View at Publisher · View at Google Scholar · View at Scopus
  26. F. Vittone, A. Liberman, D. Vasic et al., “Sitagliptin reduces plaque macrophage content and stabilises arteriosclerotic lesions in Apoe−/− mice,” Diabetologia, vol. 55, no. 8, pp. 2267–2275, 2012. View at Publisher · View at Google Scholar · View at Scopus
  27. M. Vila, V. Jackson-Lewis, C. Guégan et al., “The role of glial cells in Parkinson's disease,” Current Opinion in Neurology, vol. 14, no. 4, pp. 483–489, 2001. View at Publisher · View at Google Scholar · View at Scopus
  28. N. Ao, J. Yang, X. Wang, and J. Du, “Glucagon-like peptide-1 preserves non-alcoholic fatty liver disease through inhibition of the endoplasmic reticulum stress-associated pathway,” Hepatology Research, 2015. View at Publisher · View at Google Scholar · View at Scopus
  29. R. O. Crajoinas, F. T. Oricchio, T. D. Pessoa et al., “Mechanisms mediating the diuretic and natriuretic actions of the incretin hormone glucagon-like peptide-1,” The American Journal of Physiology—Renal Physiology, vol. 301, no. 2, pp. F355–F363, 2011. View at Publisher · View at Google Scholar · View at Scopus
  30. S. Gou, T. Zhu, W. Wang, M. Xiao, X.-C. Wang, and Z.-H. Chen, “Glucagon like peptide-1 attenuates bleomycin-induced pulmonary fibrosis, involving the inactivation of NF-κB in mice,” International Immunopharmacology, vol. 22, no. 2, pp. 498–504, 2014. View at Publisher · View at Google Scholar · View at Scopus
  31. A. E. Hogan, A. M. Tobin, T. Ahern et al., “Glucagon-like peptide-1 (GLP-1) and the regulation of human invariant natural killer T cells: lessons from obesity, diabetes and psoriasis,” Diabetologia, vol. 54, no. 11, pp. 2745–2754, 2011. View at Publisher · View at Google Scholar · View at Scopus
  32. M. Dorecka, K. Siemianowicz, T. Francuz et al., “Exendin-4 and GLP-1 decreases induced expression of ICAM-1, VCAM-1 and RAGE in human retinal pigment epithelial cells,” Pharmacological Reports, vol. 65, no. 4, pp. 884–890, 2013. View at Publisher · View at Google Scholar · View at Scopus
  33. J.-W. Yoon and H.-S. Jun, “Autoimmune destruction of pancreatic β cells,” American Journal of Therapeutics, vol. 12, no. 6, pp. 580–591, 2005. View at Publisher · View at Google Scholar · View at Scopus
  34. C. R. Kahn, “Banting lecture: insulin action, diabetogenes, and the cause of type II diabetes,” Diabetes, vol. 43, no. 8, pp. 1066–1084, 1994. View at Publisher · View at Google Scholar · View at Scopus
  35. G. M. Reaven, “Banting lecture 1988. Role of insulin resistance in human disease,” Diabetes, vol. 37, no. 12, pp. 1595–1607, 1988. View at Google Scholar
  36. S. I. Taylor, D. Accili, and Y. Imai, “Insulin resistance or insulin deficiency. Which is the primary cause of NIDDM?” Diabetes, vol. 43, no. 6, pp. 735–740, 1994. View at Publisher · View at Google Scholar · View at Scopus
  37. S. Cernea and M. Dobreanu, “Diabetes and beta cell function: from mechanisms to evaluation and clinical implications,” Biochemia Medica, vol. 23, no. 3, pp. 266–280, 2013. View at Publisher · View at Google Scholar · View at Scopus
  38. P. A. Halban, K. S. Polonsky, D. W. Bowden et al., “β-Cell failure in type 2 diabetes: postulated mechanisms and prospects for prevention and treatment,” Diabetes Care, vol. 37, no. 6, pp. 1751–1758, 2014. View at Publisher · View at Google Scholar · View at Scopus
  39. M. Cnop, N. Welsh, J.-C. Jonas, A. Jörns, S. Lenzen, and D. L. Eizirik, “Mechanisms of pancreatic β-cell death in type 1 and type 2 diabetes: many differences, few similarities,” Diabetes, vol. 54, supplement 2, pp. S97–S107, 2005. View at Publisher · View at Google Scholar · View at Scopus
  40. I. L. Campbell, A. Iscaro, and L. C. Harrison, “IFN-γ and tumor necrosis factor-α: cytotoxicity to murine islets of Langerhans,” Journal of Immunology, vol. 141, no. 7, pp. 2325–2329, 1988. View at Google Scholar · View at Scopus
  41. C. Park, J.-R. Kim, J.-K. Shim et al., “Inhibitory effects of streptozotocin, tumor necrosis factor-α, and interleukin-1β on glucokinase activity in pancreatic islets and gene expression of GLUT2 and glucokinase,” Archives of Biochemistry and Biophysics, vol. 362, no. 2, pp. 217–224, 1999. View at Publisher · View at Google Scholar · View at Scopus
  42. M. Y. Donath, J. A. Ehses, K. Maedler et al., “Mechanisms of β-cell death in type 2 diabetes,” Diabetes, vol. 54, supplement 2, pp. S108–S113, 2005. View at Publisher · View at Google Scholar · View at Scopus
  43. C. Huang, L. Yuan, and S. Cao, “Endogenous GLP-1 as a key self-defense molecule against lipotoxicity in pancreatic islets,” International Journal of Molecular Medicine, vol. 36, no. 1, pp. 173–185, 2015. View at Publisher · View at Google Scholar · View at Scopus
  44. K. Velmurugan, A. N. Balamurugan, G. Loganathan, A. Ahmad, B. J. Hering, and S. Pugazhenthi, “Antiapoptotic actions of exendin-4 against hypoxia and cytokines are augmented by CREB,” Endocrinology, vol. 153, no. 3, pp. 1116–1128, 2012. View at Publisher · View at Google Scholar · View at Scopus
  45. L. Tian, J. Gao, J. Hao et al., “Reversal of new-onset diabetes through modulating inflammation and stimulating β-cell replication in nonobese diabetic mice by a dipeptidyl peptidase IV inhibitor,” Endocrinology, vol. 151, no. 7, pp. 3049–3060, 2010. View at Publisher · View at Google Scholar · View at Scopus
  46. A. S. Akarte, B. P. Srinivasan, S. Gandhi, and S. Sole, “Chronic DPP-IV inhibition with PKF-275-055 attenuates inflammation and improves gene expressions responsible for insulin secretion in streptozotocin induced diabetic rats,” European Journal of Pharmaceutical Sciences, vol. 47, no. 2, pp. 456–463, 2012. View at Publisher · View at Google Scholar · View at Scopus
  47. Y. Zhang, Y. Chen, J. Cheng, Z. Guo, Y. Lu, and B. Tian, “DPP IV inhibitor suppresses STZ-induced islets injury dependent on activation of the IGFR/Akt/mTOR signaling pathways by GLP-1 in monkeys,” Biochemical and Biophysical Research Communications, vol. 456, no. 1, pp. 139–144, 2015. View at Publisher · View at Google Scholar · View at Scopus
  48. U. Pugazhenthi, K. Velmurugan, A. Tran, G. Mahaffey, and S. Pugazhenthi, “Anti-inflammatory action of exendin-4 in human islets is enhanced by phosphodiesterase inhibitors: potential therapeutic benefits in diabetic patients,” Diabetologia, vol. 53, no. 11, pp. 2357–2368, 2010. View at Publisher · View at Google Scholar · View at Scopus
  49. S. R. Cechin, I. Pérez-Álvarez, E. Fenjves et al., “Anti-inflammatory properties of exenatide in human pancreatic islets,” Cell Transplantation, vol. 21, no. 4, pp. 633–648, 2012. View at Publisher · View at Google Scholar · View at Scopus
  50. H. Kanda, S. Tateya, Y. Tamori et al., “MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity,” The Journal of Clinical Investigation, vol. 116, no. 6, pp. 1494–1505, 2006. View at Publisher · View at Google Scholar · View at Scopus
  51. S. P. Weisberg, D. Hunter, R. Huber et al., “CCR2 modulates inflammatory and metabolic effects of high-fat feeding,” Journal of Clinical Investigation, vol. 116, no. 1, pp. 115–124, 2006. View at Publisher · View at Google Scholar · View at Scopus
  52. S. Winer, Y. Chan, G. Paltser et al., “Normalization of obesity-associated insulin resistance through immunotherapy,” Nature Medicine, vol. 15, no. 8, pp. 921–929, 2009. View at Publisher · View at Google Scholar · View at Scopus
  53. T. M. Jensen, K. Saha, and W. M. Steinberg, “Is there a link between liraglutide and pancreatitis? A post hoc review of pooled and patient-level data from completed liraglutide type 2 diabetes clinical trials,” Diabetes Care, vol. 38, pp. 1058–1066, 2015. View at Google Scholar
  54. A. S. Franks, P. H. Lee, and C. M. George, “Pancreatitis: a potential complication of liraglutide?” Annals of Pharmacotherapy, vol. 46, no. 11, pp. 1547–1553, 2012. View at Publisher · View at Google Scholar · View at Scopus
  55. P. C. Butler, M. Elashoff, R. Elashoff, and E. A. M. Gale, “A critical analysis of the clinical use of incretin-based therapies: are the GLP-1 therapies safe?” Diabetes Care, vol. 36, no. 7, pp. 2118–2125, 2013. View at Publisher · View at Google Scholar · View at Scopus
  56. P. J. Pussinen, K. Tuomisto, P. Jousilahti, A. S. Havulinna, J. Sundvall, and V. Salomaa, “Endotoxemia, immune response to periodontal pathogens, and systemic inflammation associate with incident cardiovascular disease events,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 27, no. 6, pp. 1433–1439, 2007. View at Publisher · View at Google Scholar · View at Scopus
  57. C. J. Kelly, S. P. Colgan, and D. N. Frank, “Of microbes and meals: the health consequences of dietary endotoxemia,” Nutrition in Clinical Practice, vol. 27, no. 2, pp. 215–225, 2012. View at Publisher · View at Google Scholar · View at Scopus
  58. J. Frostegård, “Immunity, atherosclerosis and cardiovascular disease,” BMC Medicine, vol. 11, article 117, 2013. View at Publisher · View at Google Scholar · View at Scopus
  59. K. C. Dozier, E. L. Cureton, R. O. Kwan, B. Curran, J. Sadjadi, and G. P. Victorino, “Glucagon-like peptide-1 protects mesenteric endothelium from injury during inflammation,” Peptides, vol. 30, no. 9, pp. 1735–1741, 2009. View at Publisher · View at Google Scholar · View at Scopus
  60. N. M. Krasner, Y. Ido, N. B. Ruderman, and J. M. Cacicedo, “Glucagon-Like Peptide-1 (GLP-1) analog liraglutide inhibits endothelial cell inflammation through a calcium and AMPK dependent mechanism,” PLoS ONE, vol. 9, no. 5, Article ID e97554, 2014. View at Publisher · View at Google Scholar · View at Scopus
  61. Y. Hattori, T. Jojima, A. Tomizawa et al., “A glucagon-like peptide-1 (GLP-1) analogue, liraglutide, upregulates nitric oxide production and exerts anti-inflammatory action in endothelial cells,” Diabetologia, vol. 53, no. 10, pp. 2256–2263, 2010. View at Publisher · View at Google Scholar · View at Scopus
  62. A. Shiraki, J.-I. Oyama, H. Komoda et al., “The glucagon-like peptide 1 analog liraglutide reduces TNF-α-induced oxidative stress and inflammation in endothelial cells,” Atherosclerosis, vol. 221, no. 2, pp. 375–382, 2012. View at Publisher · View at Google Scholar · View at Scopus
  63. Y. Wang, E. T. Parlevliet, J. J. Geerling et al., “Exendin-4 decreases liver inflammation and atherosclerosis development simultaneously by reducing macrophage infiltration,” British Journal of Pharmacology, vol. 171, no. 3, pp. 723–734, 2014. View at Publisher · View at Google Scholar · View at Scopus
  64. Y. Dai, D. Dai, X. Wang, Z. Ding, and J. L. Mehta, “DPP-4 inhibitors repress NLRP3 inflammasome and interleukin-1beta via GLP-1 receptor in macrophages through protein kinase C pathway,” Cardiovascular Drugs and Therapy, vol. 28, no. 5, pp. 425–432, 2014. View at Publisher · View at Google Scholar · View at Scopus
  65. H. M. Salim, D. Fukuda, Y. Higashikuni et al., “Dipeptidyl peptidase-4 inhibitor, linagliptin, ameliorates endothelial dysfunction and atherogenesis in normoglycemic apolipoprotein-E deficient mice,” Vascular Pharmacology, vol. 79, pp. 16–23, 2015. View at Publisher · View at Google Scholar · View at Scopus
  66. Y. Zeng, C. Li, M. Guan et al., “The DPP-4 inhibitor sitagliptin attenuates the progress of atherosclerosis in apolipoprotein-E-knockout mice via AMPK- and MAPK-dependent mechanisms,” Cardiovascular Diabetology, vol. 13, article 32, 2014. View at Publisher · View at Google Scholar · View at Scopus
  67. S. Tang, Q. Zhang, H. Tang et al., “Effects of glucagon-like peptide-1 on advanced glycation endproduct-induced aortic endothelial dysfunction in streptozotocin-induced diabetic rats: possible roles of Rho kinase- and AMP kinase-mediated nuclear factor κB signaling pathways,” Endocrine, pp. 1–10, 2016. View at Publisher · View at Google Scholar
  68. J. Matsubara, S. Sugiyama, K. Sugamura et al., “A dipeptidyl peptidase-4 inhibitor, des-fluoro-sitagliptin, improves endothelial function and reduces atherosclerotic lesion formation in apolipoprotein E-deficient mice,” Journal of the American College of Cardiology, vol. 59, no. 3, pp. 265–276, 2012. View at Publisher · View at Google Scholar · View at Scopus
  69. K. Akita, K. Isoda, K. Shimada, and H. Daida, “Dipeptidyl-peptidase-4 inhibitor, alogliptin, attenuates arterial inflammation and neointimal formation after injury in low-density lipoprotein (LDL) receptor-deficient mice,” Journal of the American Heart Association, vol. 4, no. 3, Article ID e001469, 2015. View at Publisher · View at Google Scholar
  70. M. Burgmaier, A. Liberman, J. Möllmann et al., “Glucagon-like peptide-1 (GLP-1) and its split products GLP-1(9-37) and GLP-1(28-37) stabilize atherosclerotic lesions in apoe-/- mice,” Atherosclerosis, vol. 231, no. 2, pp. 427–435, 2013. View at Publisher · View at Google Scholar · View at Scopus
  71. M. Lappas, “Anti-inflammatory properties of sirtuin 6 in human umbilical vein endothelial cells,” Mediators of Inflammation, vol. 2012, Article ID 597514, 11 pages, 2012. View at Publisher · View at Google Scholar · View at Scopus
  72. X. Du, X. Hu, and J. Wei, “Anti-inflammatory effect of exendin-4 postconditioning during myocardial ischemia and reperfusion,” Molecular Biology Reports, vol. 41, no. 6, pp. 3853–3857, 2014. View at Publisher · View at Google Scholar · View at Scopus
  73. Y. Cai, X. Hu, B. Yi, T. Zhang, and Z. Wen, “Glucagon-like peptide-1 receptor agonist protects against hyperglycemia-induced cardiocytes injury by inhibiting high mobility group box 1 expression,” Molecular Biology Reports, vol. 39, no. 12, pp. 10705–10711, 2012. View at Publisher · View at Google Scholar · View at Scopus
  74. Y.-S. Liu, Z.-W. Huang, L. Wang et al., “Sitagliptin alleviated myocardial remodeling of the left ventricle and improved cardiac diastolic dysfunction in diabetic rats,” Journal of Pharmacological Sciences, vol. 127, no. 3, pp. 260–274, 2015. View at Publisher · View at Google Scholar · View at Scopus
  75. M. L. Block and J.-S. Hong, “Microglia and inflammation-mediated neurodegeneration: multiple triggers with a common mechanism,” Progress in Neurobiology, vol. 76, no. 2, pp. 77–98, 2005. View at Publisher · View at Google Scholar · View at Scopus
  76. E. G. McGeer and P. L. McGeer, “The role of anti-inflammatory agents in Parkinson's disease,” CNS Drugs, vol. 21, no. 10, pp. 789–797, 2007. View at Publisher · View at Google Scholar · View at Scopus
  77. R. E. Mrak and W. S. T. Griffin, “Glia and their cytokines in progression of neurodegeneration,” Neurobiology of Aging, vol. 26, no. 3, pp. 349–354, 2005. View at Publisher · View at Google Scholar · View at Scopus
  78. E. M. C. Schrijvers, J. C. M. Witteman, E. J. G. Sijbrands, A. Hofman, P. J. Koudstaal, and M. M. B. Breteler, “Insulin metabolism and the risk of Alzheimer disease: the Rotterdam Study,” Neurology, vol. 75, no. 22, pp. 1982–1987, 2010. View at Publisher · View at Google Scholar · View at Scopus
  79. C. Kappe, L. M. Tracy, C. Patrone, K. Iverfeldt, and Å. Sjöholm, “GLP-1 secretion by microglial cells and decreased CNS expression in obesity,” Journal of Neuroinflammation, vol. 9, article 276, 2012. View at Publisher · View at Google Scholar · View at Scopus
  80. T. Perry and N. H. Greig, “Enhancing central nervous system endogenous GLP-1 receptor pathways for intervention in Alzheimer's disease,” Current Alzheimer Research, vol. 2, no. 3, pp. 377–385, 2005. View at Publisher · View at Google Scholar · View at Scopus
  81. C. Holscher, “Incretin analogues that have been developed to treat type 2 diabetes hold promise as a novel treatment strategy for Alzheimer's disease,” Recent Patents on CNS Drug Discovery, vol. 5, no. 2, pp. 109–117, 2010. View at Publisher · View at Google Scholar · View at Scopus
  82. A. Harkavyi and P. S. Whitton, “Glucagon-like peptide 1 receptor stimulation as a means of neuroprotection,” British Journal of Pharmacology, vol. 159, no. 3, pp. 495–501, 2010. View at Publisher · View at Google Scholar · View at Scopus
  83. A. Hamilton and C. Hölscher, “Receptors for the incretin glucagon-like peptide-1 are expressed on neurons in the central nervous system,” NeuroReport, vol. 20, no. 13, pp. 1161–1166, 2009. View at Publisher · View at Google Scholar · View at Scopus
  84. A. Hamilton, S. Patterson, D. Porter, V. A. Gault, and C. Holscher, “Novel GLP-1 mimetics developed to treat type 2 diabetes promote progenitor cell proliferation in the brain,” Journal of Neuroscience Research, vol. 89, no. 4, pp. 481–489, 2011. View at Publisher · View at Google Scholar · View at Scopus
  85. K. Hunter and C. Hölscher, “Drugs developed to treat diabetes, liraglutide and lixisenatide, cross the blood brain barrier and enhance neurogenesis,” BMC Neuroscience, vol. 13, article 33, 2012. View at Publisher · View at Google Scholar · View at Scopus
  86. P. L. Mcclean, V. Parthsarathy, E. Faivre, and C. Holscher, “The diabetes drug liraglutide prevents degenerative processes in a mouse model of Alzheimer's disease,” The Journal of Neuroscience, vol. 31, no. 17, pp. 6587–6594, 2011. View at Publisher · View at Google Scholar · View at Scopus
  87. N. Gong, Q. Xiao, B. Zhu et al., “Activation of spinal glucagon-like peptide-1 receptors specifically suppresses pain hypersensitivity,” Journal of Neuroscience, vol. 34, no. 15, pp. 5322–5334, 2014. View at Publisher · View at Google Scholar · View at Scopus
  88. K. Plaschke and S. Hoyer, “Action of the diabetogenic drug streptozotocin on glycolytic and glycogenolytic metabolism in adult rat brain cortex and hippocampus,” International Journal of Developmental Neuroscience, vol. 11, no. 4, pp. 477–483, 1993. View at Publisher · View at Google Scholar · View at Scopus
  89. V. Solmaz, B. P. Çınar, G. Yiğittürk, T. Çavuşoğlu, D. Taşkıran, and O. Erbaş, “Exenatide reduces TNF-α expression and improves hippocampal neuron numbers and memory in streptozotocin treated rats,” European Journal of Pharmacology, vol. 765, pp. 482–487, 2015. View at Publisher · View at Google Scholar · View at Scopus
  90. T. Iwai, T. Sawabe, K. Tanimitsu, M. Suzuki, S. Sasaki-Hamada, and J.-I. Oka, “Glucagon-like peptide-1 protects synaptic and learning functions from neuroinflammation in rodents,” Journal of Neuroscience Research, vol. 92, no. 4, pp. 446–454, 2014. View at Publisher · View at Google Scholar · View at Scopus
  91. P. L. McClean and C. Hölscher, “Liraglutide can reverse memory impairment, synaptic loss and reduce plaque load in aged APP/PS1 mice, a model of Alzheimer's disease,” Neuropharmacology, vol. 76, pp. 57–67, 2014. View at Publisher · View at Google Scholar · View at Scopus
  92. C. Hölscher, “The incretin hormones glucagonlike peptide 1 and glucose-dependent insulinotropic polypeptide are neuroprotective in mouse models of Alzheimer's disease,” Alzheimer's & Dementia, vol. 10, no. 1, pp. S47–S54, 2014. View at Publisher · View at Google Scholar · View at Scopus
  93. M. D'Amico, C. Di Filippo, R. Marfella et al., “Long-term inhibition of dipeptidyl peptidase-4 in Alzheimer's prone mice,” Experimental Gerontology, vol. 45, no. 3, pp. 202–207, 2010. View at Publisher · View at Google Scholar · View at Scopus
  94. S. Kim, M. Moon, and S. Park, “Exendin-4 protects dopaminergic neurons by inhibition of microglial activation and matrix metalloproteinase-3 expression in an animal model of Parkinson's disease,” The Journal of Endocrinology, vol. 202, no. 3, pp. 431–439, 2009. View at Publisher · View at Google Scholar · View at Scopus
  95. J. Lee, S.-W. Hong, S. W. Chae et al., “Exendin-4 improves steatohepatitis by increasing Sirt1 expression in high-fat diet-induced obese C57BL/6J mice,” PLoS ONE, vol. 7, no. 2, Article ID e31394, 2012. View at Publisher · View at Google Scholar · View at Scopus
  96. F. Xu, Z. Li, X. Zheng et al., “SIRT1 mediates the effect of GLP-1 receptor agonist exenatide on ameliorating hepatic steatosis,” Diabetes, vol. 63, no. 11, pp. 3637–3646, 2014. View at Publisher · View at Google Scholar · View at Scopus
  97. Y. Eguchi, Y. Kitajima, H. Hyogo et al., “Pilot study of liraglutide effects in non-alcoholic steatohepatitis and non-alcoholic fatty liver disease with glucose intolerance in Japanese patients (LEAN-J),” Hepatology Research, vol. 45, no. 3, pp. 269–278, 2015. View at Publisher · View at Google Scholar · View at Scopus
  98. G. Derosa, I. G. Franzetti, F. Querci et al., “Exenatide plus metformin compared with metformin alone on β-cell function in patients with Type 2 diabetes,” Diabetic Medicine, vol. 29, no. 12, pp. 1515–1523, 2012. View at Publisher · View at Google Scholar · View at Scopus
  99. M. Saraheimo, A.-M. Teppo, C. Forsblom, J. Fagerudd, and P.-H. Groop, “Diabetic nephropathy is associated with low-grade inflammation in Type 1 diabetic patients,” Diabetologia, vol. 46, no. 10, pp. 1402–1407, 2003. View at Publisher · View at Google Scholar · View at Scopus
  100. C. D. A. Stehouwer, M.-A. Gall, J. W. R. Twisk, E. Knudsen, J. J. Emeis, and H.-H. Parving, “Increased urinary albumin excretion, endothelial dysfunction, and chronic low-grade inflammation in type 2 diabetes: progressive, interrelated, and independently associated with risk of death,” Diabetes, vol. 51, no. 4, pp. 1157–1165, 2002. View at Publisher · View at Google Scholar · View at Scopus
  101. R. Kodera, K. Shikata, H. U. Kataoka et al., “Glucagon-like peptide-1 receptor agonist ameliorates renal injury through its anti-inflammatory action without lowering blood glucose level in a rat model of type 1 diabetes,” Diabetologia, vol. 54, no. 4, pp. 965–978, 2011. View at Publisher · View at Google Scholar · View at Scopus
  102. P. Schlatter, C. Beglinger, J. Drewe, and H. Gutmann, “Glucagon-like peptide 1 receptor expression in primary porcine proximal tubular cells,” Regulatory Peptides, vol. 141, no. 1–3, pp. 120–128, 2007. View at Publisher · View at Google Scholar · View at Scopus
  103. S. Sancar-Bas, S. Gezginci-Oktayoglu, and S. Bolkent, “Exendin-4 attenuates renal tubular injury by decreasing oxidative stress and inflammation in streptozotocin-induced diabetic mice,” Growth Factors, vol. 33, no. 5-6, pp. 419–429, 2015. View at Publisher · View at Google Scholar
  104. M. Gangadharan Komala, S. Gross, A. Zaky, C. Pollock, and U. Panchapakesan, “Saxagliptin reduces renal tubulointerstitial inflammation, hypertrophy and fibrosis in diabetes,” Nephrology, 2015. View at Publisher · View at Google Scholar
  105. R. Kodera, K. Shikata, T. Takatsuka et al., “Dipeptidyl peptidase-4 inhibitor ameliorates early renal injury through its anti-inflammatory action in a rat model of type 1 diabetes,” Biochemical and Biophysical Research Communications, vol. 443, no. 3, pp. 828–833, 2014. View at Publisher · View at Google Scholar · View at Scopus
  106. S. Nakashima, T. Matsui, M. Takeuchi, and S.-I. Yamagishi, “Linagliptin blocks renal damage in type 1 diabetic rats by suppressing advanced glycation end products-receptor axis,” Hormone and Metabolic Research, vol. 46, no. 10, pp. 717–721, 2014. View at Publisher · View at Google Scholar · View at Scopus
  107. Y. Higashijima, T. Tanaka, J. Yamaguchi, S. Tanaka, and M. Nangaku, “Anti-inflammatory role of DPP-4 inhibitors in a nondiabetic model of glomerular injury,” The American Journal of Physiology—Renal Physiology, vol. 308, no. 8, pp. F878–F887, 2015. View at Publisher · View at Google Scholar · View at Scopus
  108. D. Katagiri, Y. Hamasaki, K. Doi et al., “Protection of glucagon-like peptide-1 in cisplatin-induced renal injury elucidates gut-kidney connection,” Journal of the American Society of Nephrology, vol. 24, no. 12, pp. 2034–2043, 2013. View at Publisher · View at Google Scholar · View at Scopus
  109. Y.-T. Chen, T.-H. Tsai, C.-C. Yang et al., “Exendin-4 and sitagliptin protect kidney from ischemia-reperfusion injury through suppressing oxidative stress and inflammatory reaction,” Journal of Translational Medicine, vol. 11, article 270, 2013. View at Publisher · View at Google Scholar · View at Scopus
  110. T. Zhu, X.-L. Wu, W. Zhang, and M. Xiao, “Glucagon like peptide-1 (GLP-1) modulates OVA-induced airway inflammation and mucus secretion involving a protein kinase A (PKA)-dependent nuclear factor-κB (NF-κB) signaling pathway in mice,” International Journal of Molecular Sciences, vol. 16, no. 9, pp. 20195–20211, 2015. View at Publisher · View at Google Scholar · View at Scopus
  111. E. Zhang, F. Xu, H. Liang et al., “GLP-1 receptor agonist exenatide attenuates the detrimental effects of obesity on inflammatory profile in testis and sperm quality in mice,” American Journal of Reproductive Immunology, vol. 74, no. 5, pp. 457–466, 2015. View at Publisher · View at Google Scholar · View at Scopus
  112. H. W. Bakos, R. C. Henshaw, M. Mitchell, and M. Lane, “Paternal body mass index is associated with decreased blastocyst development and reduced live birth rates following assisted reproductive technology,” Fertility and Sterility, vol. 95, no. 5, pp. 1700–1704, 2011. View at Publisher · View at Google Scholar · View at Scopus
  113. D. J. Drucker and C. F. Rosen, “Glucagon-like peptide-1 (GLP-1) receptor agonists, obesity and psoriasis: diabetes meets dermatology,” Diabetologia, vol. 54, no. 11, pp. 2741–2744, 2011. View at Publisher · View at Google Scholar · View at Scopus
  114. A. Faurschou, F. K. Knop, J. P. Thyssen, C. Zachariae, L. Skov, and T. Vilsbøll, “Improvement in psoriasis after treatment with the glucagon-like peptide-1 receptor agonist liraglutide,” Acta Diabetologica, vol. 51, no. 1, pp. 147–150, 2014. View at Publisher · View at Google Scholar · View at Scopus
  115. S. Steven, M. Hausding, S. Kröller-Schön et al., “Gliptin and GLP1 analog treatment improves survival and vascular inflammation/dysfunction in animals with lipopolysaccharideinduced endotoxemia,” Basic Research in Cardiology, vol. 110, no. 2, article 6, 2015. View at Publisher · View at Google Scholar · View at Scopus