Renoprotective Effects of the Dipeptidyl Peptidase-4 Inhibitor Sitagliptin: A Review in Type 2 Diabetes

Journal of Diabetes Research

Volumn 2017, Issue , 2017, Pages

  Mega, Cristina ^a,b   Teixeira De Lemos, Edite ^a   Fernandes, Rosa ^b,c   Reis, Flávio ^b,c  

^a POLYTECHNIC INSTITUTE OF VISEU   (Portugal)

^b UNIVERSITY OF COIMBRA   (Portugal)

^c UNIVERSITY OF COIMBRA   (Portugal)

Author keywords

[No Author keywords available]

Indexed keywords

INCRETIN; SITAGLIPTIN; DIPEPTIDYL PEPTIDASE IV INHIBITOR; PROTECTIVE AGENT;

CELL PROTECTION; DIABETIC NEPHROPATHY; DRUG EFFECT; HUMAN; KIDNEY FUNCTION; KIDNEY INJURY; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PATHOPHYSIOLOGY; RENAL PROTECTION; REVIEW; TREATMENT OUTCOME;

DIABETES MELLITUS, TYPE 2; DIABETIC NEPHROPATHIES; DIPEPTIDYL-PEPTIDASE IV INHIBITORS; HUMANS; PROTECTIVE AGENTS; SITAGLIPTIN PHOSPHATE; TREATMENT OUTCOME;

EID: 85042691127     PISSN: 23146745     EISSN: 23146753     Source Type: Journal    
DOI: 10.1155/2017/5164292     Document Type: Review

References (199)

1. M. Virally, J. F. Blickle, J. Girard, S. Halimi, D. Simon, and P. J. Guillausseau, "Type 2 diabetes mellitus: epidemiology, pathophysiology, unmet needs and therapeutical perspectives," Diabetic Medicine, vol. 33, pp. 231-244, 2007.
2. S. E. Kahn, "The importance of the β-cell in the pathogenesis of type 2 diabetes mellitus," American Journal of Medicine, vol. 108, pp. 2S-8S, 2000.
3. P. Marchetti, R. Lupi, S. D. Guerra, M. Bugliani, L. Marselli, and U. Boggi, "The β-cell in human type 2 diabetes," Advances in Experimental Medicine and Biology, vol. 654, pp. 501-514, 2010.
4. M. E. Cerf, "Beta cell dysfunction and insulin resistance," Frontiers in Endocrinology, vol. 4, p. 37, 2013.
5. S. Yagihashi, W. Inaba, and H. Mizukami, "Dynamic pathology of islet endocrine cells in type 2 diabetes: b-cell growth, death, regeneration and their clinical implications," Journal ofDiabetes Investigation, vol. 7, pp. 155-165, 2016.
6. R. A. D. Fronzo, "From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus (banting lecture)," Diabetes, vol. 58, pp. 773-795, 2009.
7. D. J. Drucker, "The biology of incretin hormones," Cell Metabolism, vol. 3, no. 3, pp. 153-165, 2006.
8. 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.
9. M. K. Piya, P. G. McTernan, and S. Kumar, "Adipokine inflammation and insulin resistance: the role of glucose, lipids and endotoxin," Journal of Endocrinology, vol. 216, pp. T1-T15, 2013.
10. S. Guo, "Insulin signaling, resistance, and metabolic syndrome: insights from mouse models into disease mechanisms," Journal ofEndocrinology, vol. 220, pp. T1-T23, 2014.
11. U. J. Jung and M.-S. Choi, "Obesity and its metabolic complications: the role of adipokines and the relationship between obesity, inflammation, insulin resistance, dyslipid-emia and nonalcoholic fatty liver disease," International Journal of Molecular Sciences, vol. 15, no. 4, pp. 61846223, 2014.
12. S. L. Lay, G. Simard, M. C. Martinez, and R. Andriantsito-haina, "Oxidative stress and metabolic pathologies: from an adipocentric point of view," Oxidative Medicine and Cellular Longevity, vol. 2014, Article ID 908539, 18 pages, 2014.
13. L. Chen, R. Chen, H. Wang, and F. Liang, "Mechanisms linking inflammation to insulin resistance," International Journal of Endocrinology, vol. 2015, Article ID 508409, 9 pages, 2015.
14. S. Tangvarasittichai, "Oxidative stress, insulin resistance, dyslipidemia and type 2 diabetes mellitus," World Journal ofDiabetes, vol. 6, no. 3, pp. 456-480, 2015.
15. K. N. Keane, V. F. Cruzat, R. Carlessi, P. I. H. de Bittencourt, and P. Newsholme, "Molecular events linking oxidative stress and inflammation to insulin resistance and β-cell dysfunction," Oxidative Medicine and Cellular Longevity, vol. 2015, Article ID 181643, 15 pages, 2015.
16. E. J. Bae, "DPP-4 inhibitors in diabetic complications: role of DPP-4 beyond glucose control," Archives of Pharmacal Research, vol. 39, no. 8, pp. 1114-1128, 2016.
17. L. A. Filla and J. L. Edwards, "Metabolomics in diabetic complications," Molecular BioSystems, vol. 12, pp. 10901105, 2016.
18. A. Chawla, R. Chawla, and S. Jaggi, "Microvasular and macrovascular complications in diabetes mellitus: distinct or continuum?," Indian Journal of Endocrinology and Metabolism, vol. 20, no. 4, pp. 546-551, 2016.
19. A. Mima, "Incretin-based therapy for prevention of diabetic vascular complications," Journal ofDiabetes Research, vol. 2016, Article ID 1379274, 12 pages, 2016.
20. T. S. Kern, "Contributions of inflammatory processes to the development of the early stages of diabetic retinopathy," Journal ofDiabetes Research, vol. 2007, Article ID 95103, 14 pages, 2007.
21. J. F. Navarro-Gonzalez and C. Mora-Fernandez, "The role of inflammatory cytokines in diabetic nephropathy," Journal ofthe American Society ofNephrology, vol. 19, pp. 433-442, 2008.
22. A. M. Vincent, B. C. Callaghan, A. L. Smith, and E. L. Feldman, "Diabetic neuropathy: cellular mechanisms as therapeutic targets," Nature Reviews Neurology, vol.7, pp.573-583, 2011.
23. M. Narres, H. Claessen, S. Droste et al., "The incidence of end-stage renal disease in the diabetic (compared to the non-diabetic) population: a systematic review," PLoS One, vol. 11, no. 1, article e0147329, 2016.
24. J. A. J. G. Van den Brand , "Diabetes mellitus as a cause of end-stage renal disease in Europe: signs of improvement," Clinical Kidney Journal, vol. 9, no. 3, pp. 454-456, 2016.
25. American Diabetes Association, "Stand ards of medical care in diabetes-2017," Diabetes Care, vol. 40, Supplement 1, 2017.
26. M. Y. Donath, D. M. Schumann, M. Faulenbach, H. Ellingsgaard, A. Perren, and J. A. Ehses, "Islet inflammation in type 2 diabetes: from metabolic stress to therapy," Diabetes Care, vol. 31, no. 2, pp. S161-S164, 2008.
27. W. J. Rejeski, E. H. Ip, A. G. Bertoni et al., "Lifestyle change and mobility in obese adults with type 2 diabetes," New England Journal of Medicine, vol. 366, no. 13, pp. 12091217, 2012.
28. J. J. Marin-Penalver, I. Martin-Timon, C. Sevillano-Collantes, and F. J. del Canizo-Gomez, "Update on the treatment of type 2 diabetes mellitus," World Journal ofDiabetes, vol. 7, no. 17, pp. 354-395, 2016.
29. R. Khardori, "Type 2 diabetes mellitus medication," Meds-cape, May 2017, http://emedicine.medscape.com/article/117853-overview.
30. R. Godinho, C. Mega, E. Teixeira-de-Lemos et al., "The place of dipeptidyl peptidase-4 inhibitors in type 2 diabetes therapeutics: a "me too" or "the special one" antidiabetic class?," Journal ofDiabetes Research, vol. 2015, Article ID 806979, 28 pages, 2015.
31. "International Diabetes Federation (IDF) 2014," https://www.idf.org/about-diabetes/what-is-diabetes.
32. D. M. Nathan, P. McGee, M. W. Steffes, J. M. Lachin, and DCCT/EDIC Research Group, "Relationship of glycated albumin to blood glucose and HbA1c values and to retinopa-thy, nephropathy, and cardiovascular outcomes in the DCCT/EDIC study," Diabetes, vol. 63, pp. 282-290, 2014.
33. National Institute for Health and Care Excellence (NICE), "Type 2 diabetes in adults: management. NICE guidelines [NG28] 2015," April 2017, https://www.nice.org.uk/guidance/ng28/chapter/1-recommendations.
34. American Diabetes Association (ADA), "Strategies for Improving Care," Diabetes Care, vol. 39, Supplement 1, pp. S6-S12, 2016.
35. S. Ayadurai, H. L. Hattingh, L. B. G. Tee, and S. N. Md Said, "A narrative review of diabetes intervention studies to explore diabetes care opportunities for pharmacists," Journal ofDiabetes Research, vol. 2016, Article ID 5897452, 11 pages, 2016.
36. G. Rayman, "Glycaemic control, glucose variability and the triangle of diabetes care," British Journal of Diabetes, vol. 16, Supplement 1, pp. S3-S6, 2016.
37. S. E. Kahn, M. E. Cooper, and S. D. Prato, "Pathophysiology and treatment of type 2 diabetes: perspectives on the past, present, and future," TheLancet, vol. 383, pp. 1068-1083,2014.
38. S. E. Inzucchi, R. M. Bergenstal, J. B. Buse et al., "Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)," Diabetes Care, vol. 35, no. 6, pp. 1364-1379, 2012.
39. M. Mata-Cases, D. Mauricio, and J. Franch-Nadal, "Clinical characteristics of type 2 diabetic patients on basal insulin therapy with adequate fasting glucose control who do not achieve HbA1c targets," Journal of Diabetes, vol. 9, no. 1, pp. 34-44, 2017.
40. D. Russell-Jones and S. Gough, "Recent advances in incretin-based therapies," Clinical Endocrinology, vol. 77, no. 4, pp. 489-499, 2012.
41. B. L. Wajchenberg, "β-cell failure in diabetes and preservation by clinical treatment," Endocrine Reviews, vol. 28, no. 2, pp. 187-218, 2017.
42. W. T. Cefalu, "The physiologic role of incretin hormones: clinical applications," Journal ofthe American Osteopathic Association, vol. 110, no. 3, Supplement 2, pp. S8-S14, 2010.
43. M. C. Riddle, "Glycemic management of type 2 diabetes: an emerging strategy with oral agents, insulins, and combinations," Endocrinology and Metabolism Clinics of North America, vol. 34, pp. 77-98, 2005.
44. A. A. Hasan and B. Hocher, "Role of soluble and membrane-bounddipeptidylpeptidase-4indiabeticnephrop-athy," Journal ofMolecular Endocrinology, vol. 59, no. 1, pp. R1-R10, 2017.
45. J. E. Gerich, "Role of the kidney in normal glucose homeo-stasis and in the hyperglycaemia of diabetes mellitus: therapeutic implications," Diabetic Medicine, vol. 27, no. 2, pp. 136-142, 2010.
46. M. A. Nauck, "Update on developments with SGLT2 inhibitors in the management of type 2 diabetes," Drug Design Development and Therapy, vol. 8, pp. 1335-1380, 2014.
47. H. Noh and G. L. King, "The role ofprotein kinase C activation in diabetic nephropathy," Kidney International, vol. 106, pp. S49-S53, 2007.
48. N. Tanji, G. S. Markowitz, C. Fu et al., "Expression of advanced glycation end products and their cellular receptor RAGE in diabetic nephropathy and nondiabetic renal disease," Journal of the American Society of Nephrology, vol. 11, no. 9, pp. 1656-1666, 2000.
49. K. Susztak, A. C. Raff, M. Schiffer, and E. P. Bottinger, "Glucose-induced reactive oxygen species cause apoptosis of podocytes and podocyte depletion at the onset of diabetic nephropathy," Diabetes, vol. 55, no. 1, pp. 225-233, 2006.
50. J. M. Forbes, M. T. Coughlan, and M. E. Cooper, "Oxidative stress as a major culprit in kidney disease in diabetes," Diabetes, vol. 57, no. 6, pp. 1446-1454, 2008.
51. Z. Cao and M. E. Cooper, "Pathogenesis of diabetic nephropathy," Journal of Diabetes Investigation, vol. 2, no. 4, pp. 243247, 2011.
52. D. K. Singh, P. Winocour, and K. Farrington, "Oxidative stress in early diabetic nephropathy: fueling the fire," Nature Reviews Endocrinology, vol. 7, no. 3, pp. 176-184, 2011.
53. X. Chen, Z. Ren, W. Liang et al., "c-Abl mediates angiotensin II-induced apoptosis in podocytes," Journal of Molecular Histology, vol. 44, no. 5, pp. 597-608, 2013.
54. V. P. Singh, A. Bali, N. Singh, and A. S. Jaggi, "Advanced glycation end products and diabetic complications," The Korean Journal of Physiology & Pharmacology, vol. 18, no. 1, pp. 1-14, 2014.
55. A. Rivero, C. Mora, M. Muros, J. Garcia, H. Herrera, and J. F. Navarro-Gonzalez, "Pathogenic perspectives for the role of inflammation in diabetic nephropathy," Clinical Science, vol. 116, no. 6, pp. 479-492, 2009.
56. P. Gao, F.-F. He, H. Tang et al., "NADPH oxidase-induced NALP3 inflammasome activation is driven by thioredoxin-interacting protein which contributes to podocyte injury in hyperglycemia," Journal ofDiabetes Research, vol. 2015, Article ID 504761, 12 pages, 2015.
57. K. Kanasaki, G. Taduri, and D. Koya, "Diabetic nephropathy: the role of inflammation in fibroblast activation and kidney fibrosis," Frontiers in Endocrinology, vol. 4, p. 7, 2013.
58. M. B. Duran-Salgado and A. F. Rubio-Guerra, "Diabetic nephropathy and inflammation," World Journal of Diabetes, vol. 5, no. 3, pp. 393-398, 2014.
59. S. Morano, R. Cipriani, C. Santangelo et al., "Angiotensin blockade and matrix synthesis by glomerular epithelial cells in high glucose: a further experimental insight into the path-ophysiology of diabetic nephropathy," Clinical Therapeutics, vol. 159, no. 3, pp. 151-154, 2008.
60. T. Chawla, D. Sharma, and A. Singh, "Role ofthe renin angio-tensin system in diabetic nephropathy," World Journal of Diabetes, vol. 1, no. 5, pp. 141-145, 2010.
61. M. H. A. Muskiet, M. M. Smits, L. M. Morsink, and M. Diamant, "The gut-renal axis: do incretin-based agents confer renoprotection in diabetes?," Nature Reviews Nephrology, vol. 10, pp. 88-103, 2014.
62. S. M. Marshall, "Recent advances in diabetic nephropa-thy," Postgraduate Medical Journal, vol. 80, pp. 624-633, 2004.
63. E. Bortoloso, D. D. Prete, M. Dalla Vestra et al., "Quantitative and qualitative changes in vascular endothelial growth factor gene expression in glomeruli of patients with type 2 diabetes," European Journal ofEndocrinology, vol. 150, pp. 799-807, 2004.
64. H. J. Baelde, M. Eikmans, D. W. Lappin et al., "Reduction of VEGF-A and CTGF expression in diabetic nephropathy is associated with podocyte loss," Kidney International, vol. 71, pp. 637-645, 2007.
65. J. J. Li, S. J. Kwak, D. S. Jung et al., "Podocyte biology in diabetic nephropathy," Kidney International, vol. 106, pp. S36-S42, 2007.
66. J. S. Lin and K. Susztak, "Podocytes: the weakest link in diabetic kidney disease?," Current Diabetes Reports, vol. 16, no. 5, p. 45, 2016.
67. J. R. Sowers, A. Whaley-Connell, and M. R. Hayden, "The role of overweight and obesity in the cardiorenal syndrome," Cardiorenal Medicine, vol. 1, pp. 5-12, 2011.
68. 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, pp. 120-128, 2007.
69. A. Aroor, S. McKarns, R. Nistala et al., "DPP-4 inhibitors as therapeutic modulators of immune cell function and associated cardiovascular and renal insulin resistance in obesity and diabetes," Cardiorenal Medicine, vol. 3, no. 1, pp. 4856, 2013.
70. M. Yu, C. Moreno, K. M. Hoagland et al., "Antihypertensive effect of glucagonlike peptide 1 in Dahl salt-sensitive rats," Journal ofHypertension, vol. 21, pp. 1125-1135, 2003.
71. E. P. Jensen, S. S. Poulsen, H. Kissow et al., "Activation of GLP-1 receptors on vascular smooth muscle cells reduces the autoregulatory response in afferent arterioles and increases renal blood flow," American Journal of Physiology-Renal Physiology, vol. 308, no. 8, pp. F867-F877, 2015.
72. T. A. Salles, L. dos Santos, V. G. Barauna, and A. C. C. Girardi, "Potential role of dipeptidyl peptidase IV in the pathophysiology of heart failure," International Journal of Molecular Sciences, vol. 16, no. 2, pp. 4226-4249, 2015.
73. E. E. Mulvihill and D. J. Drucker, "Metabolic implications of DPP-4 inhibition," Endocrine Reviews, vol. 35, no. 6, pp. 992-1019, 2014.
74. K. V. Websky, C. Reichetzedera, and B. Hochera, "Physiology and pathophysiology of incretins in the kidney," Current Opinion in Nephrology and Hypertension, vol. 23, no. 1, pp. 54-60, 2014.
75. S. Shi, D. Koya, and K. Kanasaki, "Dipeptidyl peptidase-4 and kidney fibrosis in diabetes," Fibrogenesis & Tissue Repair, vol. 9, p. 1, 2016.
76. G. P. Fadini, E. Boscaro, M. Albiero et al., "The oral dipepti-dyl peptidase-4 inhibitor sitagliptin increases circulating endothelial progenitor cells in patients with type 2 diabetes mellitus. Possible role of stromal derived factor-1a," Diabetes Care, vol. 33, pp. 1607-1609, 2010.
77. G. L. Plosker, "Sitagliptin: a review of its use in patients with type 2 diabetes mellitus," Drugs, vol. 74, pp. 223-242, 2014.
78. G. A. Herman, C. Stevens, K. Van Dyck et al., "Pharmacoki-netics and pharmacodynamics of sitagliptin, an inhibitor of dipeptidyl peptidase IV, in healthy subjects: results from two rand omized, double-blind, placebo-controlled studies with single oral doses," Journal of Clinical Pharmacology and Therapeutics, vol. 78, no. 6, pp. 675-688, 2005.
79. A. J. Bergman, J. Cote, B. Yi et al., "Effect of renal insufficiency on the pharmacokinetics of sitagliptin, a dipepti-dyl peptidase-4 inhibitor," Diabetes Care, vol. 30, no. 7, pp. 1862-1864, 2007.
80. E. M. Migoya, C. H. Stevens, A. J. Bergman et al., "Effect of moderate hepatic insufficiency on the pharmacokinetics of sitagliptin," Canadian Journal of Clinical Pharmacology, vol. 16, no. 1, pp. 165-170, 2009.
81. J. C. Arjona Ferreira, M. Marre, N. Barzilai et al., "Efficacy and safety of sitagliptin versus glipizide in patients with type 2 diabetes and moderate-to-severe chronic renal insufficiency," Diabetes Care, vol. 36, no. 5, pp. 1067-1073, 2013.
82. J. J. Neumiller and I. B. Hirsch, "Management ofhyperglyce-mia in diabetic kidney disease," Diabetes Spectrum, vol. 28, no. 3, pp. 214-219, 2015.
83. C. C. R. Betonico, S. M. O. Titan, M. L. C. Correa-Giannella, M. Nery, and M. Queiroz, "Management of diabetes mellitus in individuals with chronic kidney disease: therapeutic perspectives and glycemic control," Clinics, vol. 71, no. 1, pp. 47-53, 2016.
84. D. Kim, L. Wang, M. Beconi et al., "2(2R)-4-oxo-4-[3-(tri-fluoromethyl)-5,6-dihydro[1, 2, 4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine: a potent, orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes," Journal ofMedicinal Chemistry, vol. 48, no. 1, pp. 141-151, 2005.
85. S. E. Inzucchi and D. K. McGuire, "New drugs for the treatment of diabetes: part II. Incretin-based therapy and beyond," Circulation, vol. 117, no. 4, pp. 574-584, 2008.
86. B. Ahren, "Dipeptidyl peptidase-4 inhibitors: clinical data and clinical implications," Diabetes Care, vol. 30, no. 6, pp. 1344-1350, 2007.
87. R. K. Campbell, "Rationale for dipeptidyl peptidase 4 inhibitors: a new class of oral agents for the treatment of type 2 diabetes mellitus," Annals of Pharmacotherapy, vol. 41, no. 1, pp. 51-60, 2007.
88. J. Rosenstock and B. Zinman, "Dipeptidyl peptidase-4 inhibitors and the management of type 2 diabetes mellitus," Current Opinion in Endocrinology, Diabetes, and Obesity, vol. 14, no. 2, pp. 98-107, 2007.
89. L. L. Baggio and D. J. Drucker, "Biology of incretins: GLP-1 and GIP," Gastroenterology, vol. 132, no. 6, pp. 21312157, 2007.
90. J. F. Gautier, S. P. Choukem, and J. Girard, "Physiology of incretins (GIP and GLP-1) and abnormalities in type 2 diabetes," Diabetes & Metabolism, vol. 34, Supplement 2, pp. S65-S72, 2008.
91. C. F. Deacon, P. Danielsen, L. Klarskov, M. Olesen, and J. J. Holst, "Dipeptidyl peptidase IV inhibition reduces the degradation and clearance of GIP and potentiates its insu-linotropic and antihyperglycemic effects in anesthetized pigs," Diabetes, vol. 50, no. 7, pp. 1588-1597, 2001.
92. G. A. Herman, A. Bergman, F. Liu et al., "Pharmacokinetics and pharmacodynamic effects of the oral DPP-4 inhibitor sitagliptin in middle-aged obese subjects," Journal ofClinical Pharmacology, vol. 46, no. 8, pp. 876-886, 2006.
93. B. Ahren, E. Simonsson, H. Larsson et al., "Inhibition of dipeptidyl peptidase IV improves metabolic control over a 4-week study period in type 2 diabetes," Diabetes Care, vol. 25, no. 5, pp. 869-875, 2002.
94. B. Ahren, "Insulin plus incretin: a glucose-lowering strategy for type 2-diabetes," World Journal ofDiabetes, vol. 5, no. 1, pp. 40-51, 2014.
95. A. J. Scheen, "Pharmacokinetics of dipeptidylpeptidase-4 inhibitors," Diabetes Obesity and Metabolism, vol. 12, no. 8, pp. 648-658, 2010.
96. S. S. Engel, E. Round, G. T. Golm, K. D. Kaufman, and B. J. Goldstein, "Safety and tolerability of sitagliptin in type 2 diabetes: pooled analysis of 25 clinical studies," Diabetes Therapy, vol. 4, no. 1, pp. 119-145, 2013.
97. K. Garg, C. D. Tripathi, and S. Kumar, "Clinical review of sitagliptin: a DPP-4 inhibitor," Journal ofthe Association of Physicians of India, vol. 61, pp. 57-61, 2013.
98. K. Esposito, P. Chiodini, M. I. Maiorino, G. Bellastella, A. Capuano, and D. Giugliano, "Glycaemic durability with dipeptidyl peptidase-4 inhibitors in type 2 diabetes: a systematic review and meta-analysis of long-term rand omised controlled trials," BMJ Open, vol. 4, article e005442, 2014.
99. J. Mu, J. Woods, and Y. P. Zhou, "Chronic inhibition of dipeptidyl peptidase-4 with a sitagliptin analog preserves pancreatic β-cell mass and function in a rodent model of type 2 diabetes," Diabetes, vol. 55, no. 6, pp. 1695-1704, 2006.
100. J. Mu, A. Petrov, G. J. Eiermann et al., "Inhibition of DPP-4 with sitagliptin improves glycemic control and restores islet cell mass and function in a rodent model of type 2 diabetes," European Journal ofPharmacology, vol. 623, pp. 148-154, 2009.
101. L. Ferreira, E. Teixeira-de-Lemos, F. Pinto et al., "Effects of sitagliptin treatment on dysmetabolism, inflammation, and oxidative stress in an animal model of type 2 diabetes (ZDF rat)," Mediators of Inflammation, vol. 2010, Article ID 592760, 11 pages, 2010.
102. M. Ji, L. Xia, J. Cao, and D. Zou, "Sitagliptin/metformin versus insulin glargine combined with metformin in obese subjects with newly diagnosed type 2 diabetes," Medicine, vol. 95, no. 11, article e2961, 2016.
103. Y. Kondo, N. Harada, A. Hamasaki et al., "Sitagliptin monotherapy has better effect on insulinogenic index than glimepiride monotherapy in Japanese patients with type 2 diabetes mellitus: a 52-week, multicenter, parallel-group rand omized controlled trial," Diabetology & Metabolic Syndrome, vol. 8, no. 15, 2016.
104. X. Ren, G. Liu, Y. Wang et al., "Influence of dipeptidyl peptidase-IV inhibitor sitagliptin on extracellular signal-regulated kinases 1/2 signaling in rats with diabetic nephrop-athy," Pharmacology, vol. 100, pp. 1-13, 2017.
105. B. Gallwitz, "Extra-pancreatic effects of incretin-based therapies," Endocrine, vol. 47, no. 2, pp. 360-371, 2014.
106. E. J. Verspohl, "Novel therapeutics for type 2 diabetes: incre-tin hormone mimetics (glucagon-like-peptide-1 receptor agonists) and dipeptidyl peptidase-4 inhibitors," Pharmacology & Therapeutics, vol. 124, pp. 113-138, 2009.
107. R. E. Van Genugten, D. H. van Raalte, and M. Diamant, "Dipeptidyl peptidase-4 inhibitors and preservation of pancreatic islet-cell function: a critical appraisal of the evidence," Diabetes Obesity and Metabolism, vol. 14, pp. 101-111,2012.
108. 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, no. 32, 2014.
109. A. V. Matveyenko, S. Dry, H. I. Cox et al., "Beneficial endocrine but adverse exocrine effects of sitagliptin in the human islet amyloid polypeptide transgenic rat model oftype 2 diabetes: interactions with metformin," Diabetes, vol. 58, no. 7, pp. 1604-1615, 2009.
110. 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.
111. L. M. McCormick, A. C. Kydd, P. A. Read et al., "Chronic dipeptidyl peptidase-4 inhibition with sitagliptin is associated with sustained protection against ischemic left ventricular dysfunction in a pilot study of patients with type 2 diabetes mellitus and coronaryarterydisease," Circulation: Cardiovascular Imaging, vol. 7, no. 2, pp. 274-281, 2014.
112. N. Apaijai, H. Pintana, S. C. Chattipakorn, and N. Chattipakorn, "Effects of vildagliptin versus sitagliptin, on cardiac function, heart rate variability and mitochondrial function in obese insulin resistant rats," British Journal of Pharmacology, vol. 169, no. 5, pp. 1048-1057, 2013.
113. B. Picatoste, E. Ramirez, A. Caro-Vadillo et al., "Sitagliptin reduces cardiac apoptosis, hypertrophy and fibrosis primarily by insulin-dependent mechanisms in experimental type-II diabetes. Potential roles of GLP-1 isoforms," PLoS One, vol. 8, no. 10, article e78330, 2013.
114. P. A. Read, F. Z. Khan, P. M. Heck, S. P. Hoole, and D. P. Dutka, "DPP-4 inhibition by sitagliptin improves the myocardial response to dobutamine stress and mitigates stunning in a pilot study of patients with coronary artery disease," Circulation. Cardiovascular Imaging, vol. 3, no. 2, pp. 195-201, 2010.
115. M. T. Kelleni, E. F. Amin, and A. M. Abdelrahman, "Effect of metformin and sitagliptin on doxorubicin-induced cardio-toxicity in rats: impact of oxidative stress, inflammation, and apoptosis," Journal ofToxicology, vol. 2015, Article ID 424813, 8 pages, 2015.
116. T. Mita, N. Katakami, T. Shiraiwa et al., "Sitagliptin attenuates the progression of carotid intima-media thickening in insulin-treated patients with type 2 diabetes: the sitagliptin preventive study of intima-media thickness evaluation (spike): a rand omized controlled trial," Diabetes Care, vol. 39, no. 3, pp. 455-464, 2016.
117. R. E. Amori, J. Lau, and A. G. Pittas, "Efficacy and safety of incretin therapy in type 2 diabetes: systematic review and meta-analysis," Journal ofthe American Medical Association, vol. 298, no. 2, pp. 194-206, 2007.
118. M. Fan, Y. Li, and S. Zhang, "Effects of sitagliptin on lipid profiles in patients with type 2 diabetes mellitus: a meta-analysis of rand omized clinical trials," Medicine, vol. 95, no. 2, pp. 1-9, 2016.
119. P. C. M. Van Poppel, M. G. Netea, P. Smits, and C. Tack, "Vildagliptin improves endothelium-dependent vasodilata-tion in type 2 diabetes," Diabetes Care, vol. 34, no. 9, pp. 2072-2077, 2011.
120. J. S. Yoon and H. W. Lee, "Understand ing the cardiovascular effects of incretin," Diabetes & Metabolism Journal, vol. 35, no. 5, pp. 437-443, 2011.
121. C. Mega, H. Vala, P. Rodrigues-Santos et al., "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," Diabetology & Metabolic Syndrome, vol. 6, no. 1, p. 42, 2014.
122. A. Gonçalves, E. Leal, A. Paiva et al., "Protective effects of the dipeptidyl peptidase IV inhibitor sitagliptin in the blood-retinal barrier in a type 2 diabetes animal model," Diabetes, Obesity and Metabolism, vol. 14, no. 5, pp. 454-463, 2012.
123. A. Gonçalves, C. Marques, E. Leal et al., "Dipeptidyl peptidase-IV inhibition prevents blood-retinal barrier breakdown, inflammation and neuronal cell death in the retina of type 1 diabetic rats," Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, vol. 1842, no. 9, pp. 1454-1463, 2014.
124. C. Mega, E. T. de Lemos, H. Vala et al., "Diabetic nephropa-thy amelioration by a low dose sitagliptin in an animal model of type 2 diabetes (Zucker diabetic fatty rat)," Experimental Diabetes Research, vol. 2011, Article ID 162092, 12 pages, 2011.
125. A. Maida, T. Hansotia, C. Longuet, T. Seino, and D. J. Drucker, "Differential importance of glucose-dependent insulinotropic polypeptide vs glucagon-like peptide 1 receptor signaling for ft cell survival in mice," Gastroenterology, vol. 137, pp. 2146-2157, 2009.
126. J. A. Yeom, E. S. Kim, H. S. Park et al., "Both sitagliptin analogue & pioglitazone preserve the ft-cell proportion in the islets with different mechanism in non-obese and obese diabetic mice," BMB Reports, vol. 44, no. 11, pp. 713-718, 2011.
127. Y. Takeda, Y. Fujita, and J. Honjo, "Reduction of both beta cell death and alpha cell proliferation by dipeptidyl peptidase-4 inhibition in a streptozotocin-induced model of diabetes in mice," Diabetologia, vol. 55, no. 2, pp. 404-412, 2012.
128. S. Karabulut, Z. M. Coskunb, and S. Bolkent, "Immuno-histochemical, apoptotic and biochemical changes by dipeptidyl peptidase-4 inhibitor-sitagliptin in type-2 diabetic rats," Pharmacological Reports, vol. 67, no. 5, pp. 846-853, 2015.
129. J. Shirakawa, T. Okuyama, M. Kyohara et al., "DPP-4 inhibition improves early mortality, ft cell function, and adipose tissue inflammation in db/db mice fed a diet containing sucrose and linoleic acid," Diabetology & Metabolic Syndrome, vol. 8, no. 16, 2016.
130. 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," American Journal ofPhysiology: Endocrinology and Metabolism, vol. 300, no. 2, pp. E410-E421, 2011.
131. N. Satoh-Asahara, Y. Sasaki, H. Wada et al., "A dipeptidyl peptidase-4 inhibitor, sitagliptin, exerts anti-inflammatory effects in type 2 diabetic patients," Metabolism, vol. 62, no. 3, pp. 347-351, 2013.
132. G. Derosa, A. Carbone, A. D'Angelo et al., "Variations in inflammatory biomarkers following the addition of sitaglip-tin in patients with type 2 diabetes not controlled with met-formin," Internal Medicine, vol. 52, no. 19, pp. 2179-2187, 2013.
133. F. Beguinot, "Tribbles homologue 3 (TRIB3) and the insulin-resistance genes in type 2 diabetes," Diabetologia, vol. 53, pp. 1831-1834, 2010.
134. S. Prudente, D. Scarpelli, M. Chandalia et al., "The trib3 Q84R polymorphism and risk ofearly-onset type 2 diabetes," Journal of Clinical Endocrinology & Metabolism, vol. 94, no. 1, pp. 190-196, 2009.
135. J. Shirakawa, H. Fujii, K. Ohnuma et al., "Diet-induced adipose tissue inflammation and liver steatosis are prevented by DPP-4 inhibition in diabetic mice," Diabetes, vol. 60, pp. 1246-1257, 2011.
136. S. Oyadomari, H. P. Harding, Y. Zhang, M. Oyadomari, and D. Ron, "Dephosphorylation of translation initiation factor 2a enhances glucose tolerance and attenuates hepa-tosteatosis in mice," Cell Metabolism, vol. 7, pp. 520-532, 2008.
137. V. Aviv, I. Meivar-Levy, I. H. Rachmut, T. Rubinek, E. Mor, and S. Ferber, "Exendin-4 promotes liver cell proliferation and enhances PDX-1-induced liver to pancreas transdifferen-tiation," The Journal ofBiological Chemistry, vol. 284, no. 48, pp. 33509-33520, 2009.
138. L. Gaetaniello, M. Fiore, S. de Filippo, N. Pozzi, S. Tamasi, and C. Pignata, "Occupancy of dipeptidyl peptidase IV activates an associated tyrosine kinase and triggers an apoptotic signal in human hepatocarcinoma cells," Hepatology, vol. 27, pp. 934-942, 1998.
139. M. E. Kelany, T. M. Hakami, A. H. Omar, and M. A. Abdallah, "Combination of sitagliptin and insulin against type 2 diabetes mellitus with neuropathy in rats: neuroprotec-tion and role of oxidative and inflammation stress," Pharmacology, vol. 98, pp. 242-250, 2016.
140. B. F. Schrijvers, A. Flyvbjerg, R. G. Tilton, N. H. Lameire, and A. S. D. Vriese, "A neutralizing VEGF antibody prevents glo-merular hypertrophy in a model of obese type 2 diabetes, the Zucker diabetic fatty rat," Nephrology Dialysis Transplantation, vol. 21, no. 2, pp. 324-329, 2006.
141. L. Liu, J. Liu, W. T. Wong et al., "Dipeptidyl peptidase 4 inhibitor sitagliptin protects endothelial function in hypertension through a glucagon-like peptide 1-dependent mechanism," Hypertension, vol. 60, pp. 833-841, 2012.
142. S. Kroller-Schon, M. Knorr, M. Hausding et al., "Glucose-independent improvement of vascular dysfunction in experimental sepsis by dipeptidyl-peptidase 4 inhibition," Cardiovascular Research, vol. 96, pp. 140-149, 2012.
143. I. Kawasaki, Y. Hiura, A. Tamai et al., "Sitagliptin reduces the urine albumin-to-creatinine ratio in type 2 diabetes through decreasing both blood pressure and estimated glomerular filtration rate," Journal ofDiabetes, vol. 7, no. 1, pp. 41-46, 2015.
144. L. M. Russo, R. M. Sandoval, S. B. Campos, B. A. Molitoris, W. D. Comper, and D. Brown, "Impaired tubular uptake explains albuminuria in early diabetic nephropathy," Journal of the American Society of Nephrology, vol. 20, no. 3, pp. 489494, 2009.
145. G. B. Peres and Y. M. Michelacci, "The role of proximal tubular cells in the early stages of diabetic nephropathy," Journal ofDiabetes & Metabolism, vol. 6, p. 551, 2015.
146. A. C. Girardi, B. C. Degray, T. Nagy, D. Biemesderfer, and P. S. Aronson, "Association of Na+-H+ exchanger isoform NHE3 and dipeptidyl peptidase IV in the renal proximal tubule," The Journal of Biological Chemistry, vol. 276, no. 49, pp. 46671-46677, 2001.
147. D. F. Arruda-Junior, F. L. Martins, R. Dariolli et al., "Dipep-tidyl peptidase IV inhibition exerts renoprotective effects in rats with established heart failure," Frontiers in Physiology, vol. 7, p. 293, 2016.
148. R. Nistala, J. Habibi, G. Lastra et al., "Prevention of obesity-induced renal injury in male mice by DPP4 inhibition," Endocrinology, vol. 155, no. 6, pp. 2266-2276, 2014.
149. R. Nistala, J. Habibi, A. Aroor et al., "DPP4 inhibition attenuates filtration barrier injury and oxidant stress in the zucker obese rat," Obesity, vol. 22, no. 10, pp. 21722179, 2014.
150. W. J. Liu, S. H. Xie, Y. N. Liu et al., "Dipeptidyl peptidase IV inhibitor attenuates kidney injury in streptozotocin-induced diabetic rats," Journal of Pharmacology and Experimental Therapeutics, vol. 340, pp. 248-255, 2012.
151. A. Aroor, M. Zuberek, C. Duta et al., "Angiotensin II stimulation of DPP4 activity regulates megalin in the proximal tubules," International Journal ofMolecular Sciences, vol. 17, no. 5, 2016.
152. B. Hocher, C. Reichetzeder, and M. L. Alter, "Renal and cardiac effects of DPP-4 inhibitors-from preclinical development to clinical research," Kidney and Blood Pressure Research, vol. 36, pp. 65-84, 2012.
153. B. P. Pacheco, R. O. Crajoinas, G. K. Couto et al., "Dipeptidyl peptidase IV inhibition attenuates blood pressure rising in young spontaneously hypertensive rats," Journal ofHyperten-sion, vol. 29, pp. 520-528, 2011.
154. S. Saha, Y. Li, and M. B. Anand-Srivastava, "Reduced levels of cyclic AMP contribute to the enhanced oxidative stress in vascular smooth muscle cells from spontaneously hypertensive rats," Canadian Journal of Physiology and Pharmacology, vol. 86, pp. 190-198, 2008.
155. A. Avogaro and G. P. Fadini, "The effects of dipeptidyl peptidase-4 inhibition on microvascular diabetes complications," Diabetes Care, vol. 37, no. 10, pp. 2884-2894, 2014.
156. A. A. Eddy, "Serine proteases, inhibitors and receptors in renal fibrosis," Thrombosis and Haemostasis, vol. 101, no. 4, pp. 656-664, 2009.
157. G. Tramonti and Y. S. Kanwar, "Tubular biomarkers to assess progression of diabetic nephropathy," Kidney International, vol. 79, no. 10, pp. 1042-1044, 2011.
158. S. Hoshi, Y. Shu, F. Yoshida et al., "Podocyte injury promotes progressive nephropathy in zucker diabetic fatty rats," Laboratory Investigation, vol. 82, no. 1, pp. 25-35, 2002.
159. N. Gassler, M. Elger, B. Kranzlin et al., "Podocyte injury underlies the progression of focal segmental glomerulosclero-sis in the fa/fa Zucker rat," Kidney International, vol. 60, no. 1, pp. 106-116, 2001.
160. T. W. Tervaert, A. L. Mooyaart, K. Amann et al., "Pathologic classification of diabetic nephropathy," Journal of the American Society of Nephrology, vol. 21, no. 4, pp. 556563, 2010.
161. K. White, "Histological appearance of diabetic nephropathy," Diapedia 7105002828 rev., no. 5, 2014.
162. U. Panchapakesan and C. Pollock, "The role of dipeptidyl peptidase-4 inhibitors in diabetic kidney disease," Frontiers in Immunology, vol. 6, p. 443, 2015.
163. H. S. Min, J. E. Kim, M. H. Lee et al., "Dipeptidyl peptidase IV inhibitor protects against renal interstitial fibrosis in a mouse model of ureteral obstruction," Laboratory Investigation, vol. 94, no. 6, pp. 598-607, 2014.
164. S. Shi, S. P. Srivastava, M. Kanasaki et al., "Interactions of DPP-4 and integrin ft1influences endothelial-to-mesenchymal transition," Kidney International, vol. 88, no. 3, pp. 479-489, 2015.
165. G. Tonolo and S. Cherchi, "Tubulointerstitial disease in diabetic nephropathy," International Journal ofNephrology and Renovascular Disease, vol. 7, pp. 107-115, 2014.
166. P. Vavrinec, R. H. Henning, S. W. Landheer et al., "Vilda-gliptin restores renal myogenic function and attenuates renal sclerosis independently of effects on blood glucose or proteinuria in Zucker diabetic fatty rat," Current Vascular Pharmacology, vol. 12, pp. 836-844, 2014.
167. I. Raz, M. Hanefeld, L. Xu et al., "Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy in patients with type 2 diabetes mellitus," Diabetologia, vol. 49, no. 11, pp. 2564-2571, 2006.
168. V. Gupta and S. Kalra, "Choosing a gliptin," Indian Journal of Endocrinology and Metabolism, vol. 15, no. 4, pp. 298-308, 2011.
169. Y. Wang, S. Landheer, W. H. van Gilst et al., "Attenuation of renovascular damage in Zucker diabetic fatty rat by NWT-03, an egg protein hydrolysate with ACE-and DPP-4-inhibitory activity," PLoS One, vol. 7, no. 10, article e46781, 2012.
170. H. Y. Jin, W. J. Liu, J. H. Park, H. S. Baek, and T. S. Park, "Effect of dipeptidyl peptidase-IV (DPP-IV) inhibitor (vildagliptin) on peripheral nerves in streptozotocin-induced diabetic rats," Archives ofMedical Research, vol. 40, pp. 536-544, 2009.
171. Y. Ishibashi, S. Yamagishi, T. Matsui et al., "Pravastatin inhibits advanced glycation end products (AGEs)-induced proximal tubular cell apoptosis and injury by reducing receptor for AGEs (RAGE) level," Metabolism, vol. 61, pp. 1067-1072, 2012.
172. T. Tanaka, Y. Higashijima, T. Wada, and M. Nangaku, "The potential for renoprotection with incretin-based drugs," Kidney International, vol. 86, pp. 701-711, 2014.
173. J. L. Gorriz, J. Nieto, J. F. Navarro-Gonzalez, P. Molina, A. Martinez-Castelao, and L. M. Pallardo, "Nephroprotection by hypoglycemic agents: do we have supporting data?," Journal of Clinical Medicine, vol. 4, no. 10, pp. 18661889, 2015.
174. W. S. Silva Junior, A. F. Godoy-Matos, and L. G. Kraemer-Aguiar, "Dipeptidyl peptidase 4: a new link between diabetes mellitus and atherosclerosis?," Biomedical Research International, vol. 2015, Article ID 816164, 10 pages, 2015.
175. V. Matheeussen, L. Baerts, G. De Meyer et al., "Expression and spatial heterogeneity of dipeptidyl peptidases in endothe-lial cells of conduct vessels and capillaries," Biological Chemistry, vol. 392, no. 3, pp. 189-198, 2011.
176. T. Romacho, S. Vallejo, L. A. Villalobos et al., "Soluble dipeptidyl peptidase-4 induces microvascular endothelial dysfunction through proteinase-activated receptor-2 and thromboxane A2 release," Journal ofHypertension, vol. 34, no. 5, pp. 869-876, 2016.
177. C. G. Yu, N. Zhang, S. S. Yuan et al., "Endothelial progenitor cells in diabetic microvascular complications: friends or foes?," Stem Cells International, vol. 2016, Article ID 1803989, 10 pages, 2016.
178. R. H. Ahmed, H. Z. Huri, Z. Al-Hamodi, S. D. Salem, and S. Muniandy, "Serum levels of soluble CD26/dipeptidyl peptidase-IV in type 2 diabetes mellitus and its association with metabolic syndrome and therapy with antidiabetic agents in Malaysian subjects," PLoS One, vol. 10, no. 10, article e0140618, 2015.
179. D. Rohrborn, N. Wronkowitz, and J. Eckel, "DPP-4 in diabetes," Frontiers in Immunology, vol. 6, p. 386, 2015.
180. J. Donate-Correa, E. Martin-Nunez, M. Muros-de-Fuentes, C. Mora-Fernandez, and J. F. Navarro-Gonzalez, "Inflammatory cytokines in diabetic nephropathy," Journal ofDiabetes Research, vol. 2015, Article ID 948417, 9 pages, 2015.
181. J. F. Navarro and C. Mora, "Diabetes, inflammation, proinflammatory cytokines, and diabetic nephropathy," The Scientific World Journal, vol. 6, pp. 908-917, 2006.
182. X. Ren, G. Liu, Y. Wang et al., "Influence of dipeptidyl peptidase-iv inhibitor sitagliptin on extracellular signal-regulated kinases 1/2 signaling in rats with diabetic nephrop-athy," Pharmacology, vol. 100, no. 1-2, pp. 1-13, 2017.
183. J. S. Nielsen and K. M. McNagny, "Novel functions of the CD34 family," Journal of Cell Science, vol. 121, Part 22, pp. 3682-3692, 2008.
184. J. H. Li, W. Wang, X. R. Huang et al., "Advanced glycation end products induce tubular epithelial-myofibroblast transition through the RAGE-ERK1/2 MAP kinase signaling pathway," The American Journal ofPathology, vol. 164, no. 4, pp. 1389-1397, 2004.
185. K. B. Gomes, K. F. Rodrigues, and A. P. Fernand es, "The role of transforming growth factor-beta in diabetic nephropathy," International Journal of Medical Genetics, vol. 2014, Article ID 180270, 6 pages, 2014.
186. F. Yang, T. Yu, K. Li, X. Jiang, J. Li, and J. Wang, "Sitagliptin reduces transforming growth factor-t1 and platelet derived growth factor-BB in regulation of UAER in type 2 diabetic nephropathy stage III patients," Biomedical Research, vol. 28, no. 6, pp. 2571-2577, 2017.
187. S. S. Bessa, T. A. Hussein, M. A. Morad, and A. M. Amer, "Urinary platelet-derived growth factor-BB as an early marker of nephropathy in patients with type 2 diabetes: an Egyptian study," Renal Failure, vol. 34, no. 6, pp. 670-675, 2012.
188. Y. Ishibashi, Y. Nishino, T. Matsui, M. Takeuchi, and S. I. Yamagishi, "Glucagon-like peptide-1 suppresses advanced glycation end product-induced monocyte chemoattractant protein-1 expression in mesangial cells by reducing advanced glycation end product receptor level," Metabolism, vol. 60, no. 9, pp. 1271-1277, 2011.
189. J. Li, M. Guan, C. Li et al., "The dipeptidyl peptidase-4 inhibitor sitagliptin protects against dyslipidemia-related kidney injury in apolipoprotein E knockout mice," International Journal ofMolecular Sciences, vol. 15, pp. 11416-11434, 2014.
190. H. S. Lee, "Mechanisms and consequences of hypertriglyc-eridemia and cellular lipid accumulation in chronic kidney disease and metabolic syndrome," Histology and Histopathol-ogy, vol. 26, no. 12, pp. 1599-1610, 2011.
191. A. R. Martins and S. Mas, "Lipotoxicity and kidney," Portuguese Journal ofNephrology & Hypertension, vol. 29, no. 4, pp. 306-315, 2015.
192. S. J. Glastras, H. Chen, R. T. McGrath et al., "Effect of GLP-1 receptor activation on offspring kidney health in a rat model of maternal obesity," Scientific Reports, vol. 6, article 23525, 2016.
193. F. A. Wagener, D. Dekker, J. H. Berden, A. Scharstuhl, and J. van der Vlag, "The role of reactive oxygen species in apo-ptosis of the diabetic kidney," Apoptosis, vol. 14, no. 12, pp. 1451-1458, 2009.
194. M. D. Sanchez-Nino, A. Benito-Martin, and A. Ortiz, "New paradigms in cell death in human diabetic nephropathy," Kidney International, vol. 78, no. 8, pp. 737-744, 2010.
195. J. Vaghasiya, N. Sheth, Y. Bhalodia, and R. Manek, "Sitaglip-tin protects renal ischemia reperfusion induced renal damage in diabetes," Regulatory Peptides, vol. 166, no. 1-3, pp. 48-54, 2011.
196. H. Hendarto, T. Inoguchi, Y. Maeda et al., "GLP-1 analog liraglutide protects against oxidative stress and albuminuria in streptozotocin-induced diabetic rats via protein kinase A mediated inhibition of renal NAD(P)H oxidases," Metabolism, vol. 61, no. 10, pp. 1422-1434, 2012.
197. R. Kodera, K. Shikata, T. Takasuta et al., "Dipeptidyl peptidase-4 inhibitor ameliorates early renal injury through its antiinflammatory action in a rat model of type 1 diabetes," Biochemical and Biophysical Research Communications, vol. 443, no. 3, pp. 828-833, 2014.
198. 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, pp. 717-721, 2014.
199. T. Matsui, S. Nakashima, Y. Nishino et al., "Dipeptidyl peptidase-4 deficiency protects against experimental diabetic nephropathy partly by blocking the advanced glycation end products-receptor axis," Laboratory Investigation, vol. 95, no. 5, pp. 525-533, 2015.