Incretin-based therapy for prevention of diabetic vascular complications

Journal of Diabetes Research

Volumn 2016, Issue , 2016, Pages

  Mima, Akira ^a  

^a KINKI UNIVERSITY SCHOOL OF MEDICINE   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIDIABETIC AGENT; DIPEPTIDYL PEPTIDASE IV INHIBITOR; INCRETIN; PROTEIN KINASE C;

ANTIINFLAMMATORY ACTIVITY; ANTIOXIDANT ACTIVITY; APOPTOSIS; ATHEROSCLEROSIS; CARDIOVASCULAR EFFECT; CEREBROVASCULAR DISEASE; CORONARY ARTERY DISEASE; DIABETIC ANGIOPATHY; DIABETIC NEPHROPATHY; DIABETIC NEUROPATHY; DIABETIC RETINOPATHY; ENZYME ACTIVATION; EPITHELIUM CELL; EXTRACELLULAR MATRIX; GLYCEMIC CONTROL; HEART FUNCTION; HEART INFARCTION; HUMAN; INFLAMMATION; INSULIN SENSITIVITY; MONOCYTE; NEUROPROTECTION; NONHUMAN; OXIDATIVE STRESS; PHASE 2 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; RENAL PROTECTION; REVIEW; ANIMAL; BRAIN CIRCULATION; CARDIOVASCULAR DISEASES; DIABETIC ANGIOPATHIES; DIABETIC NEPHROPATHIES; DIABETIC NEUROPATHIES; DRUG EFFECTS; KIDNEY; PHYSIOLOGY;

ANIMALS; CARDIOVASCULAR DISEASES; CEREBROVASCULAR CIRCULATION; DIABETIC ANGIOPATHIES; DIABETIC NEPHROPATHIES; DIABETIC NEUROPATHIES; DIPEPTIDYL-PEPTIDASE IV INHIBITORS; HUMANS; HYPOGLYCEMIC AGENTS; INCRETINS; INFLAMMATION; KIDNEY; OXIDATIVE STRESS; PROTEIN KINASE C;

EID: 84957070653     PISSN: 23146745     EISSN: 23146753     Source Type: Journal    
DOI: 10.1155/2016/1379274     Document Type: Review

References (94)

1. TheDiabetes Control and Complications Trial Research Group, "The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulindependent diabetes mellitus," The New England Journal of Medicine, vol. 329, pp. 977-986, 1993.
2. UK Prospective Diabetes Study (UKPDS) Group, "Intensive blood-glucose controlwith sulphonylureas or insulin compared with conventional treatment and risk of complications in patientswith type 2 diabetes (UKPDS 33)," The Lancet, vol. 352, no. 9131, pp. 837-853, 1998.
3. D. M. Nathan, P. A. Cleary, J.-Y. C. Backlund et al. , "Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes, The New England Journal of Medicine, vol. 353, no. 25, pp. 2643-2653, 2005.
4. R. R. Holman, S. K. Paul, M. A. Bethel, D. R. Matthews, and H. A. W. Neil, "10-Year follow-up of intensive glucose control in type 2 diabetes, The New England Journal of Medicine, vol. 359, no. 15, pp. 1577-1589, 2008.
5. D. Koya and G. L. King, "Protein kinase C activation and the development of diabetic complications," Diabetes, vol. 47, no. 6, pp. 859-866, 1998.
6. K. Naruse, C. Rask-Madsen, N. Takahara et al. , "Activation of vascular protein kinase C-beta; inhibits Akt-dependent endothelial nitric oxide synthase function in obesity-associated insulin resistance," Diabetes, vol. 55, no. 3, pp. 691-698, 2006.
7. M. Kitada, Z. Zhang, A. Mima, and G. L. King, "Molecular mechanisms of diabetic vascular complications," Journal of Diabetes Investigation, vol. 1, no. 3, pp. 77-89, 2010.
8. S. G. Coca, F. Ismail-Beigi, N. Haq, H. M. Krumholz, and C. R. Parikh, "Role of intensive glucose control in development of renal end points in type 2 diabetes mellitus: systematic review and meta-analysis," Archives of Internal Medicine, vol. 172, no. 10, pp. 761-769, 2012.
9. S. Zoungas, A. Patel, J. Chalmers et al. , "Severe hypoglycemia and risks of vascular events and death," The New England Journal of Medicine, vol. 363, no. 15, pp. 1410-1418, 2010.
10. D. J. Drucker, "The biology of incretin hormones," Cell Metabolism, vol. 3, no. 3, pp. 153-165, 2006.
11. A. Mima, J. Hiraoka-Yamomoto, Q. Li et al. , "Protective effects of GLP-1 on glomerular endothelium and its inhibition by PKCβ activation in diabetes," Diabetes, vol. 61, no. 11, pp. 2967-2979, 2012.
12. M. H. Noyan-Ashraf, M. Abdul Momen, K. Ban et al. , "GLP-1R agonist liraglutide activates cytoprotective pathways and improves outcomes after experimentalmyocardial infarction in mice," Diabetes, vol. 58, no. 4, pp. 975-983, 2009.
13. R. E. Amori, J. Lau, and A. G. Pittas, "Efficacy and safety of incretin therapy in type 2 diabetes: systematic review and metaanalysis," Journal of the American Medical Association, vol. 298, no. 2, pp. 194-206, 2007.
14. S. Devaraj, A. T. Cheung, I. Jialal et al. , "Evidence of increased inflammation and microcirculatory abnormalities in patients with type 1 diabetes and their role in microvascular complications," Diabetes, vol. 56, no. 11, pp. 2790-2796, 2007.
15. A. Treszl, L. Szereday, A. Doria, G. L. King, and T. Orban, "Elevated C-reactive protein levels do not correspond to autoimmunity in type 1 diabetes," Diabetes Care, vol. 27, no. 11, pp. 2769-2770, 2004.
16. H. Ha, M. R. Yu, Y. J. Choi, M. Kitamura, and H. B. Lee, "Role of high glucose-induced nuclear factor-βB activation in monocyte chemoattractant protein-1 expression by mesangial cells," Journal of the American Society of Nephrology, vol. 13, no. 4, pp. 894-902, 2002.
17. A. Mima, W. Qi, J. Hiraoka-Yamomoto et al. , "Retinal not systemic oxidative and inflammatory stress correlated with VEGF expression in rodent models of insulin resistance and diabetes," Investigative Ophthalmology and Visual Science, vol. 53, no. 13, pp. 8424-8432, 2012.
18. C.-C. Wu, J.-S. Chen, K.-C. Lu et al. , "Aberrant cytokines/ chemokines production correlate with proteinuria in patients with overt diabetic nephropathy," Clinica Chimica Acta, vol. 411, no. 9-10, pp. 700-704, 2010.
19. A. Mima, W. Qi, and G. L. King, "Implications of treatment that target protective mechanisms against diabetic nephropathy," Seminars in Nephrology, vol. 32, no. 5, pp. 471-478, 2012.
20. P. Xia, T. Inoguchi, T. S. Kern, R. L. Engerman, P. J. Oates, and G. L. King, "Characterization of the mechanism for the chronic activation of diacylglycerol-protein kinase C pathway in diabetes and hypergalactosemia," Diabetes, vol. 43, no. 9, pp. 1122-1129, 1994.
21. G. L. King, M. Kunisaki, Y. Nishio, T. Inoguchi, T. Shiba, and P. Xia, "Biochemical and molecular mechanisms in the development of diabetic vascular complications," Diabetes, vol. 45, supplement 3, pp. S105-S108, 1996.
22. M. Kitada, D. Koya, T. Sugimoto et al. , "Translocation of glomerular p47phox and p67phox by protein kinase C-β activation is required for oxidative stress in diabetic nephropathy," Diabetes, vol. 52, no. 10, pp. 2603-2614, 2003.
23. A. D. Hodgkinson, T. Bartlett, P. J. Oates, B. A. Millward, and A. G. Demaine, "The response of antioxidant genes to hyperglycemia is abnormal in patients with type 1 diabetes and diabetic nephropathy," Diabetes, vol. 52, no. 3, pp. 846-851, 2003.
24. Z. Zhang, K. Apse, J. Pang, and R. C. Stanton, "High glucose inhibits glucose-6-phosphate dehydrogenase via cAMP in aortic endothelial cells," The Journal of Biological Chemistry, vol. 275, no. 51, pp. 40042-40047, 2000.
25. L. A. Brondani, B. M. de Souza, G. C. K. Duarte et al. , "The UCP1 -3826A/G polymorphism is associated with diabetic retinopathy and increased UCP1 and MnSOD2 gene expression in human retina," Investigative Ophthalmology & Visual Science, vol. 53, no. 12, pp. 7449-7457, 2012.
26. A. Mezzetti, F. Cipollone, and F. Cuccurullo, "Oxidative stress and cardiovascular complications in diabetes: isoprostanes as newmarkers on an old paradigm," Cardiovascular Research, vol. 47, no. 3, pp. 475-488, 2000.
27. M. Kakimoto, T. Inoguchi, T. Sonta et al. , "Accumulation of 8-hydroxy-2'-deoxyguanosine and mitochondrial DNA deletion in kidney of diabetic rats," Diabetes, vol. 51, no. 5, pp. 1588-1595, 2002.
28. J. Leinonen, T. Lehtimki, S. Toyokuni et al. , "New biomarker evidence of oxidative DNA damage in patients with noninsulin-dependent diabetes mellitus," FEBS Letters, vol. 417, no. 1, pp. 150-152, 1997.
29. R. E. Gilbert, S. A. Kim, K. R. Tuttle et al. , "Effect of ruboxistaurin on urinary transforming growth factor-β in patients with diabetic nephropathy and type 2 diabetes," Diabetes Care, vol. 30, no. 4, pp. 995-996, 2007.
30. D. Koya, I.-K. Lee, H. Ishii, H. Kanoh, and G. L. King, "Prevention of glomerular dysfunction in diabetic rats by treatment with d-alpha-tocopherol," Journal of the American Society of Nephrology, vol. 8, no. 3, pp. 426-435, 1997.
31. J.-R. Koo and N. D. Vaziri, "Effects of diabetes, insulin and antioxidants on NO synthase abundance and NO interaction with reactive oxygen species," Kidney International, vol. 63, no. 1, pp. 195-201, 2003.
32. G. T. Mustata, M. Rosca, K. M. Biemel et al. , "Paradoxical effects of green tea (Camellia sinensis) and antioxidant vitamins in diabetic rats: improved retinopathy and renal mitochondrial defects but deterioration of collagen matrix glycoxidation and cross-linking," Diabetes, vol. 54, no. 2, pp. 517-526, 2005.
33. H. Zheng, S. A. Whitman, W. Wu et al. , "Therapeutic potential ofNrf2 activators in streptozotocin-induced diabetic nephropathy," Diabetes, vol. 60, no. 11, pp. 3055-3066, 2011.
34. H. Li, L. Zhang, F. Wang et al. , "Attenuationof glomerular injury in diabetic mice with tert-butylhydroquinone through nuclear factor erythroid 2-related factor 2-dependent antioxidant gene activation," American Journal of Nephrology, vol. 33, no. 4, pp. 289-297, 2011.
35. P. Palsamy and S. Subramanian, "Resveratrol protects diabetic kidney by attenuating hyperglycemia-mediated oxidative stress and renal inflammatory cytokines via Nrf2-Keap1 signaling," Biochimica et Biophysica Acta-Molecular Basis of Disease, vol. 1812, no. 7, pp. 719-731, 2011.
36. P. E. Pergola, M. Krauth, J. W. Huff et al. , "Effect of bardoxolone methyl on kidney function in patients with T2D and stage 3b-4 CKD," American Journal of Nephrology, vol. 33, no. 5, pp. 469-476, 2011.
37. P. E. Pergola, P. Raskin, R. D. Toto et al. , "Bardoxolone methyl and kidney function in CKD with type 2 diabetes," The New England Journal of Medicine, vol. 365, no. 4, pp. 327-336, 2011.
38. A. Psichas, F. Reimann, and F. M. Gribble, "Gut chemosensing mechanisms," The Journal of Clinical Investigation, vol. 125, no. 3, pp. 908-917, 2015.
39. B. P. Bullock, R. S. Heller, and J. F. Habener, "Tissue distribution of messenger ribonucleic acid encoding the rat glucagon-like peptide-1 receptor," Endocrinology, vol. 137, no. 7, pp. 2968-2978, 1996.
40. O. Erdogdu, D. Nathanson, A. Sjholm, T. Nystrm, and Q. Zhang, "Exendin-4 stimulates proliferation of human coronary artery endothelial cells through eNOS-, PKA-and PI3K/Aktdependent pathways and requires GLP-1 receptor," Molecular and Cellular Endocrinology, vol. 325, no. 1-2, pp. 26-35, 2010.
41. T. Nystrm, M. K. Gutniak, Q. Zhang et al. , "Effects of glucagonlike peptide-1 on endothelial function in type 2 diabetes patients with stable coronary artery disease," The American Journal of Physiology-Endocrinology and Metabolism, vol. 287, no. 6, pp. E1209-E1215, 2004.
42. T. P. Vahl, M. Tauchi, T. S. Durler et al. , "Glucagon-Like Peptide-1 (GLP-1) receptors expressed on nerve terminals in the portal vein mediate the effects of endogenous GLP-1 on glucose tolerance in rats," Endocrinology, vol. 148, no. 10, pp. 4965-4973, 2007.
43. A. Ojima, T. Matsui, S. Maeda, M. Takeuchi, and S. Yamagishi, "Glucose-dependent insulinotropic polypeptide (GIP) inhibits signaling pathways of advanced glycation end products (AGEs) in endothelial cells via its antioxidative properties," Hormone and Metabolic Research, vol. 44, no. 7, pp. 501-505, 2012.
44. L. A. Nikolaidis, D. Elahi, T. Hentosz et al. , "Recombinant glucagon-like peptide-1 increases myocardial glucose uptake and improves left ventricular performance in conscious dogs with pacing-induced dilated cardiomyopathy," Circulation, vol. 110, no. 8, pp. 955-961, 2004.
45. M. Monami, N. Marchionni, and E. Mannucci, "Glucagon-like peptide-1 receptor agonists in type 2 diabetes: a meta-analysis of randomized clinical trials," European Journal of Endocrinology, vol. 160, no. 6, pp. 909-917, 2009.
46. M. Monami, I. Iacomelli, N. Marchionni, and E. Mannucci, "Dipeptydil peptidase-4 inhibitors in type 2 diabetes: a metaanalysis of randomized clinical trials," Nutrition, Metabolism and Cardiovascular Diseases, vol. 20, no. 4, pp. 224-235, 2010.
47. 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 edeficient mice," Journal of the American College of Cardiology, vol. 59, no. 3, pp. 265-276, 2012.
48. S. Hattori, "Sitagliptin reduces albuminuria in patients with type type diabetes Endocrine Journal 58 1 69-73 2011
49. H. Fujita, H. Taniai, H. Murayama et al. , "DPP-4 inhibition with alogliptin on top of angiotensin II type 1 receptor blockade ameliorates albuminuria via up-regulation of SDF-1α in type diabetic patients with incipient nephropathy," Endocrine Journal, vol. 61, no. 2, pp. 159-166, 2014.
50. 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.
51. N. Panjwani, E. E. Mulvihill, C. Longuet et al. , "GLP-1 receptor activation indirectly reduces hepatic lipid accumulation but does not attenuate development of atherosclerosis in diabetic male ApoE-/-mice," Endocrinology, vol. 154, no. 1, pp. 127-139, 2013.
52. A. Mima, "Diabetic nephropathy: protective factors and a new therapeutic paradigm," Journal of Diabetes and Its Complications, vol. 27, no. 5, pp. 526-530, 2013.
53. P. H. Groop, M. E. Cooper, V. Perkovic et al. , "Dipeptidyl peptidase-4 inhibition with linagliptin and effects on hyperglycaemia and albuminuria in patients with type 2 diabetes and renal dysfunction: rationale and design of the MARLINA-T2D trial," Diabetes & Vascular Disease Research, vol. 12, no. 6, pp. 455-462, 2015.
54. C. W. Park, H. W. Kim, S. H. Ko et al. , "Long-term treatment of glucagon-like peptide-1 analog exendin-4 ameliorates diabetic nephropathy through improving metabolic anomalies in db/db mice," Journal of theAmerican Society of Nephrology, vol. 18, no. 4, pp. 1227-1238, 2007.
55. 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.
56. 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 Amediated inhibition of renal NAD(P)H oxidases," Metabolism: Clinical and Experimental, vol. 61, no. 10, pp. 1422-1434, 2012.
57. K. Kanasaki, S. Shi, M. Kanasaki et al. , "Linagliptinmediated DPP-4 inhibition ameliorates kidney fibrosis in streptozotocin-induced diabetic mice by inhibiting endothelialto-mesenchymal transition in a therapeutic regimen," Diabetes, vol. 63, no. 6, pp. 2120-2131, 2014.
58. H.-C. Ku and M.-J. Su, "DPP4 deficiency preserved cardiac function in abdominal aortic banding rats," PLoS ONE, vol. 9, no. 1, Article ID e85634, 2014.
59. J. B. Green, M. A. Bethel, S. K. Paul et al. , "Rationale, design, and organization of a randomized, controlled Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) in patients with type 2 diabetes and established cardiovascular disease," American Heart Journal, vol. 166, no. 6, pp. 983-989. e7, 2013.
60. Y. Ye, K. T. Keyes, C. Zhang, J. R. Perez-Polo, Y. Lin, and Y. Birnbaum, "The myocardial infarct size-limiting effect of sitagliptin is PKA-dependent, whereas the protective effect of pioglitazone is partially dependent on PKA," American Journal of Physiology: Heart and Circulatory Physiology, vol. 298, no. 5, pp. H1454-H1465, 2010.
61. N. Gomez, K. Touihri, V. Matheeussen et al. , "Dipeptidyl peptidase IV inhibition improves cardiorenal function in overpacing-induced heart failure," European Journal of Heart Failure, vol. 14, no. 1, pp. 14-21, 2012.
62. A. Takahashi, M. Asakura, S. Ito et al. , "Dipeptidyl-peptidase IV inhibition improves pathophysiology of heart failure and increases survival rate in pressure-overloaded mice," The American Journal of Physiology-Heart and Circulatory Physiology, vol. 304, no. 10, pp. H1361-H1369, 2013.
63. C. Pyke and L. B. Knudsen, "The glucagon-like peptide-1 receptor-or not?" Endocrinology, vol. 154, no. 1, pp. 4-8, 2013.
64. H. Fujita, T. Morii, H. Fujishima et al. , "The protective roles of GLP-1R signaling in diabetic nephropathy: possiblemechanism and therapeutic potential," Kidney International, vol. 85, no. 3, pp. 579-589, 2014.
65. G. Xu, H. Kaneto, D. R. Laybutt et al. , "Downregulation of GLP-1 and GIP receptor expression by hyperglycemia: possible contribution to impaired incretin effects in diabetes," Diabetes, vol. 56, no. 6, pp. 1551-1558, 2007.
66. 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: Clinical and Experimental, vol. 60, no. 9, pp. 1271-1277, 2011.
67. J.-P. Gutzwiller, S. Tschopp, A. Bock et al. , "Glucagon-like peptide 1 induces natriuresis in healthy subjects and in insulinresistant obese men," The Journal of Clinical Endocrinology & Metabolism, vol. 89, no. 6, pp. 3055-3061, 2004.
68. W. J. Liu, S. H. Xie, Y. N. Liu et al. , "Dipeptidyl peptidase IV inhibitor attenuates kidney injury in streptozotocin-induced diabetic rats," The Journal of Pharmacology and Experimental Therapeutics, vol. 340, no. 2, pp. 248-255, 2012.
69. L. L. F. Glorie, A. Verhulst, V. Matheeussen et al. , "DPP4 inhibition improves functional outcome after renal ischemiareperfusion injury, The American Journal of Physiology-Renal Physiology, vol. 303, no. 5, pp. F681-F688, 2012.
70. P. Vavrinec, R. H. Henning, S. W. Landheer et al. , "Vildagliptin 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, no. 6, pp. 836-844, 2014.
71. C. Mega, E. T. de Lemos, H. Vala et al. , "Diabetic nephropathy 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.
72. B. B. Dokken, L. R. La Bonte, G. Davis-Gorman, M. K. Teachey, N. Seaver, and P. F. McDonagh, "Glucagon-like peptide-1 (GLP-1), immediately prior to reperfusion, decreases neutrophil activation and reducesmyocardial infarct size in rodents," Hormone and Metabolic Research, vol. 43, no. 5, pp. 300-305, 2011.
73. M. Matsubara, S. Kanemoto, B. G. Leshnower et al. , "Single dose GLP-1-tf ameliorates myocardial ischemia/reperfusion injury," The Journal of Surgical Research, vol. 165, no. 1, pp. 38-45, 2011.
74. L. Timmers, J. P. S. Henriques, D. P. V. deKleijn et al. , "Exenatide reduces infarct size and improves cardiac function in a porcine model of ischemia and reperfusion injury," Journal of the American College of Cardiology, vol. 53, no. 6, pp. 501-510, 2009.
75. Y. Nogi, M. Nagashima, M. Terasaki, K. Nohtomi, T. Watanabe, and T. Hirano, "Glucose-dependent insulinotropic polypeptide prevents the progression of macrophage-driven atherosclerosis in diabetic apolipoprotein E-null mice," PLoS ONE, vol. 7, no. 4, Article ID e35683, 2012.
76. S. P. Marso, N. R. Poulter, S. E. Nissen et al. , "Design of the liraglutide effect and action in diabetes: evaluation of cardiovascular outcome results (LEADER) trial, AmericanHeart Journal, vol. 166, no. 5, pp. 823. e5-830. e5, 2013.
77. W. M. Steinberg, M. A. Nauck, B. Zinman et al. , "LEADER 3-lipase and amylase activity in subjects with type 2 diabetes baseline data from over 9000 subjects in the LEADER trial," Pancreas, vol. 43, no. 8, pp. 1223-1231, 2014.
78. 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 diabetesmellitus and coronary artery disease," Circulation: Cardiovascular Imaging, vol. 7, no. 2, pp. 274-281, 2014.
79. B. M. Scirica, D. L. Bhatt, E. Braunwald et al. , "Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus," The New England Journal of Medicine, vol. 369, no. 14, pp. 1317-1326, 2013.
80. W. B. White, C. P. Cannon, S. R. Heller et al. , "Alogliptin after acute coronary syndrome in patients with type 2 diabetes," The New England Journal ofMedicine, vol. 369, no. 14, pp. 1327-1335, 2013.
81. J. B. Green, M. A. Bethel, P. W. Armstrong et al. , "Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes," The New England Journal of Medicine, vol. 373, pp. 232-242, 2015.
82. E. Faivre, V. A. Gault, B. Thorens, and C. Hlscher, "Glucosedependent insulinotropic polypeptide receptor knockout mice are impaired in learning, synaptic plasticity, and neurogenesis," Journal of Neurophysiology, vol. 105, no. 4, pp. 1574-1580, 2011.
83. V. Darsalia, H. Ortster, A. Olverling et al. , "The DPP-4 inhibitor linagliptin counteracts stroke in the normal and diabetic mouse brain: a comparison with glimepiride," Diabetes, vol. 62, no. 4, pp. 1289-1296, 2013.
84. R. Klein, B. E. K. Klein, and S. E. Moss, "Epidemiology of proliferative diabetic retinopathy," Diabetes Care, vol. 15, no. 12, pp. 1875-1891, 1992.
85. J. W. Miller, A. P. Adamis, and L. P. Aiello, "Vascular endothelial growth factor in ocular neovascularization and proliferative diabetic retinopathy," Diabetes/Metabolism Reviews, vol. 13, no. 1, pp. 37-50, 1997.
86. E. M. Kohner, I. M. Stratton, S. J. Aldington, R. R. Holman, and D. R. Matthews, "Relationship between the severity of retinopathy and progression to photocoagulation in patients with Type 2 diabetes mellitus in the UKPDS (UKPDS 52)," Diabetic Medicine, vol. 18, no. 3, pp. 178-184, 2001.
87. The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group, "Retinopathy and nephropathy in patients with type 1 diabetes four years after a trial of intensive therapy," The New England Journal of Medicine, vol. 342, pp. 381-389, 2000.
88. Y. Zhang, J. Zhang, Q. Wang et al. , "Intravitreal injection of exendin-4 analogue protects retinal cells in early diabetic rats," Investigative Ophthalmology & Visual Science, vol. 52, no. 1, pp. 278-285, 2011.
89. Z. Fu, H.-Y. Kuang, M. Hao, X.-Y. Gao, Y. Liu, and N. Shao, "Protection of exenatide for retinal ganglion cells with different glucose concentrations," Peptides, vol. 37, no. 1, pp. 25-31, 2012.
90. A. Gonclves, E. Leal, A. Paiva et al. , "Protective effects of the dipeptidyl peptidase IVinhibitor 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.
91. A. O. Colby, "Neurologic disorders of diabetes mellitus. I," Diabetes, vol. 14, pp. 424-429, 1965.
92. A. O. Colby, "Neurologic disorders of diabetes mellitus. Ii," Diabetes, vol. 14, no. 8, pp. 516-525, 1965.
93. T. Himeno, H. Kamiya, K. Naruse et al. , "Beneficial effects of exendin-4 on experimental polyneuropathy in diabetic mice," Diabetes, vol. 60, no. 9, pp. 2397-2406, 2011.
94. W. J. Liu, H. Y. Jin, K. A. Lee, S. H. Xie, H. S. Baek, and T. S. Park, "Neuroprotective effect of the glucagon-like peptide-1 receptor agonist, synthetic exendin-4, in streptozotocin-induced diabetic rats," British Journal of Pharmacology, vol. 164, no. 5, pp. 1410-1420, 2011.