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The Possible Role of the Incretin Enhancer Sitaglipten, in Renal Ischemic Reperfusion Injury in Type 2 Diabetes Mellitus

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DOI: 10.4236/ojemd.2014.47018    2,274 Downloads   3,006 Views   Citations

ABSTRACT

Background: Diabetes mellitus (DM) especially type 2 is a major health problem and diabetic nephropathy is the main cause of end stage renal disease (ESRD). Renal ischemia/reperfusion (I/R) injury is common in diabetic patients. Recent studies reported increased vulnerability of kidneys to I/R injury in diabetic rats. In view of the reported efficacy of incretin enhancer on I/R injury. Aim: This study was designed to assess the effect of sitaglipten on renal I/R in type 2 diabetes mellitus . Methods: Type 2 DM in rats were induced by administration of nicotinamide (230 mg/kg, i.p.), 15 min prior to the single dose of streptozotocin (65 mg/kg, i.p.). Renal I/R were performed in both diabetic and normal rats. Results: The lipid peroxidation, xanthine oxidase activity, and nitric oxide levels were significantly increased after I/R in diabetic rats compared to I/R in normal rats. Antioxidant enzymes such as glutathione, superoxide dismutase, catalase, and glutathione peroxidase were significantly reduced after I/R in diabetic rats compared to normal rats. Sitaglipten treatment significantly normalized these biochemical parameters compared to diabetic I/R rats. Serum TNF-α level and myeloperoxidase activity were also significantly normalized after administration of sitaglipten. Furthermore, treatment with sitaglipten (10 mcg/kg) had preserved the normal morphology of the kidney compared to I/R performed in diabetic rats. Conclusion: Sitaglipten protects exaggerated renal I/R injury in type 2 DM. These findings have major implication in the treatment of ischemic injury that is prone to develop in DM.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

Mohamed, M. , Hammadi, S. and Hamid, M. (2014) The Possible Role of the Incretin Enhancer Sitaglipten, in Renal Ischemic Reperfusion Injury in Type 2 Diabetes Mellitus. Open Journal of Endocrine and Metabolic Diseases, 4, 181-196. doi: 10.4236/ojemd.2014.47018.

References

[1] Maisonneuve, P., Agodoa, L., Gellert, R., et al. (2000) Distribution of Primary Renal Diseases Leading to End-Stage Renal Failure in the United States, Europe, and Australia/New Zealand: Results from an International Comparative Study. American Journal of Kidney Disease, 35, 157-165.
http://dx.doi.org/10.1016/S0272-6386(00)70316-7
[2] Hokama, J.Y., Ritter, L.S., Gorman, G.D., Cimetta, A.D., Copeland, J.G. and McDonagh, P.F. (2000) Diabetes Enhances Leukocyte Accumulation in the Coronary Microcirculation Early in Reperfusion Following Ischemia. Journal of Diabetes Complication, 14, 96-107. http://dx.doi.org/10.1016/S1056-8727(00)00068-4
[3] Yellon, D.M. and Baxter, G.F. (2000) Protecting the Ischaemic and Reperfused Myocardium in Acute Myocardial Infarction: Distant Dream or Near Reality? Heart, 83, 381-387.
http://dx.doi.org/10.1136/heart.83.4.381
[4] Yokoyama, H., Okudaira, M., Otani, T., et al. (2000) Higher Incidence of Diabetic Nephropathy in Type 2 than in Type 1 Diabetes in Early-Onset Diabetes in Japan. Kidney International, 58, 302-311. http://dx.doi.org/10.1046/j.1523-1755.2000.00166.x
[5] Basireddy, M., Isbell, T.S., Teng, X., Patel, R.P. and Agarwal, A. (2006) Effects of Sodium Nitrite on Ischemia-Reperfusion Injury in the Rat Kidney. American Journal of Physiology-Renal Physiology, 290, F779-F786. http://dx.doi.org/10.1152/ajprenal.00334.2005
[6] Ysebaert, D.K., De-Greef, K.E., De-Beuf, A., et al. (2004) T Cells as Mediators in Renal Ischemia/Reperfusion Injury. Kidney International, 66, 491-496. http://dx.doi.org/10.1111/j.1523-1755.2004.761_4.x
[7] Altunoluk, B., Soylemez, H., Oguz, F., Turkmen, E. and Fadillioglu, E. (2006) An Angiotensin-Converting Enzyme Inhibitor, Zofenopril, Prevents Renal Ischemia/Reperfusion Injury in Rats. Annals of Clinical & Laboratory Science, 36, 326-332.
[8] Bolen, S., Feldman, L., Vassy, J., et al. (2007) Systematic Review: Comparative Effectiveness and Safety of Oral Medications for Type 2 Diabetes Mellitus. Annals of Internal Medicine, 147, 386-399.
[9] Taylor, S.I., Accili, D. and Imai, Y. (1994) Insulin Resistance or Insulin Deficiency. Which Is the Primary Cause of NIDDM? Diabetes, 43, 735-740. http://dx.doi.org/10.2337/diab.43.6.735
[10] Cavaghan, M.K., Ehrmann, D.A. and Polonsky, K.S. (2000) Interactions between Insulin Resistance and Insulin Secretion in the Development of Glucose Intolerance. Journal of Clinical Investigation, 106, 329-333. http://dx.doi.org/10.1172/JCI10761
[11] Holman, R.R. (2006) Long-Term Efficacy of Sulfonylureas: A United Kingdom Prospective Diabetes Study Perspective. Metabolism, 55, S2-S5. http://dx.doi.org/10.1016/j.metabol.2006.02.006
[12] Stahl, M. and Berger, W. (1999) Higher Incidence of Severe Hypoglycaemia Leading to Hospital Admission in Type 2 Diabetic Patients Treated with Long-Acting versus Short-Acting Sulphonylureas. Diabetic Medicine, 16, 586-590. http://dx.doi.org/10.1046/j.1464-5491.1999.00110.x
[13] Holst, J.J. (1997) Enteroglucagon. Annual Review of Physiology, 59, 257-271.
http://dx.doi.org/10.1146/annurev.physiol.59.1.257
[14] MacDonald, P.E., El-Kholy, W., Riedel, M.J., Salapatek, A.M., Light, P.E. and Wheeler, M.B. (2002) The Multiple Actions of GLP-1 on the Process of Glucose-Stimulated Insulin Secretion. Diabetes, 519, S434-S442.
[15] Kieffer, T.J., McIntosh, C.H. and Pederson, R.A. (1995) Degradation of Glucose-Dependent Insulinotropic Polypeptide and Truncated Glucagon-Like Peptide 1 in Vitro and in Vivo by Dipeptidyl Peptidase IV. Endocrinology, 136, 3585-3596.
[16] Raz, I., Hanefeld, M., Xu, L., Caria, C., Williams-Herman, D. and Khatami, H. (2006) Efficacy and Safety of the Dipeptidyl Peptidase-4 Inhibitor Sitagliptin as Monotherapy in Patients with Type 2 Diabetes Mellitus. Diabetologia, 49, 2564-2571. http://dx.doi.org/10.1007/s00125-006-0416-z
[17] Rosenstock, J., Baron, M.A., Dejager, S., Mills, D. and Schweizer, A. (2007) Comparison of Vildagliptin and Rosiglitazone Monotherapy in Patients with Type 2 Diabetes: A 24-Week, Double-Blind, Randomized Trial. Diabetes Care, 30, 217-223. http://dx.doi.org/10.2337/dc06-1815
[18] Rosenstock, J., Sankoh, S. and List, J.F. (2008) Glucose-Lowering Activity of the Dipeptidyl Peptidase-4 Inhibitor Saxagliptin in Drug-Naive Patients with Type 2 Diabetes. Diabetes, Obesity and Metabolism, 10, 376-386. http://dx.doi.org/10.1111/j.1463-1326.2008.00876.x
[19] Bose, A.K., Mocanu, M.M., Carr, R.D., Brand, C.L. and Yellon, D.M. (2005) Glucagon-Like Peptide 1 Can Directly Protect the Heart against Ischemia/Reperfusion Injury. Diabetes, 54, 146-151.
http://dx.doi.org/10.2337/diabetes.54.1.146
[20] Atsuo, T., Akiko, M.Y., Ryosuke, N., Yuka, S., Masahiko, H. and Masayuki, S. (2009) Antihyperglycemic Effects of ASP8497 in Streptozotocin-Nicotinamide Induced Diabetic Rats: Comparison with Other Dipeptidyl Peptidase-IV Inhibitors. Pharmacological Reports, 61, 899-908.
http://dx.doi.org/10.1016/S1734-1140(09)70147-1
[21] Bose, A.K., Mocanu, M.M., Carr, R.D. and Yellon, D.M. (2005) Glucagon Like Peptide-1 Is Protective against Myocardial Ischemia/Reperfusion Injury When Given Either as a Preconditioning Mimetic or at Reperfusion in An Isolated Rat Heart Model. Cardiovascular Drugs and Therapy, 19, 9-11.
http://dx.doi.org/10.1007/s10557-005-6892-4
[22] Masiello, P., Broca, C., Gross, R., Roye, M., Manteghetti, M., Hillaire-Buys, D., et al. (1998) Experimental NIDDM: Development of a New Model in Adult Rats Administered Streptozotocin and Nicotinamide. Diabetes, 47, 224-229. http://dx.doi.org/10.2337/diab.47.2.224
[23] Slater, T.F. and Sawyer, B.C. (1971) The Stimulatory Effects of Carbon Tetrachloride and Other Halogenoalkanes or Peroxidative Reactions in Liver Fractions in Vitro. Biochemical Journal, 123, 805-814.
[24] Moran, M.S., Depierre, J.W. and Mannervik, B. (1979) Levels of Glutathione, Glutathione Reductase and Glutathione S-Transferase Activities in Rat Lung and Liver. Biochimica et Biophysica Acta (BBA), General Subjects, 582, 67-78. http://dx.doi.org/10.1016/0304-4165(79)90289-7
[25] Misra, H.P. and Fridovich, I. (1972) The Role of Superoxide Anion in the Autooxidation of Epinephrine and a Simple Assay of SOD. Journal of Biological Chemistry, 247, 3170-3175.
[26] Aebi, H. (1984) Oxido Reductases Acting on Groups Other Than CHOH: Catalase. In: Colowick, S.P., Kaplan, N.O. and Packer, L., Eds., Methods in Enzymology, Academic Press, London, Vol. 105, 121-125.
[27] Paglia, D.E. and Valentine, W.N. (1967) Studies on the Quantitative and Qualitative Characterization of Erythrocyte Peroxidase. Journal of Laboratory and Clinical Medicine, 2, 158-169.
[28] Prajda, N. and Weber, G. (1975) Malign Transformation-Linked Imbalance: Decreased Xanthine Oxidase Activity in Hepatomas. FEBS Letters, 59, 245-249. http://dx.doi.org/10.1016/0014-5793(75)80385-1
[29] Lepoivre, G., Iwanejko, J., Dembinska-Kiec, A., Pankiewicz, J., Wanat, A., Anna, P., et al. (1998) Determination of Nitrite/Nitrate in Human Biological Material by the Simple Griess Reaction. Clinica Chimica Acta, 274, 177-188. http://dx.doi.org/10.1016/S0009-8981(98)00060-6
[30] Wei, H. and Frenkel, K. (1993) Relationship of Oxidative Events and DNA Oxidation in SENCAR Mice to in Vivo Promoting Activity of Phorbol Ester-Type Tumor Promoters. Carcinogenesis, 14, 1195-1201. http://dx.doi.org/10.1093/carcin/14.6.1195
[31] Jablonski, P., Howden, B., Rae, D., Birrel, C., Marshall, V. and Tange, J. (1983) An Experimental Model for Assessment of Renal Recovery from Warm Ischaemia. Transplantation, 35, 198-204.
http://dx.doi.org/10.1097/00007890-198303000-00002
[32] Hill, B.A. (1971) Principles of Medical Statistics. 9th Edition, Lancet Limited Publications, London, 147, 383.
[33] Umrani, D.N. and Goyal, R.K. (2003) Fenoldopam Treatment Improves Peripheral Insulin Sensitivity and Renal Function in STZ-Induced Type 2 Diabetic Rats. Clinical and Experimental Hypertension, 25, 221-233. http://dx.doi.org/10.1081/CEH-120020392
[34] Chen, H., Brahmbhatt, S., Gupta, A. and Sharma, A.C. (2005) Duration of Streptozotocin-Induced Diabetes Differentially Affects p38-Mitogen-Activated Protein Kinase (MAPK) Phosphorylation in Renal and Vascular Dysfunction. Cardiovascular Diabetology, 4, 3. http://dx.doi.org/10.1186/1475-2840-4-3
[35] Kuhad, A. and Chopra, K. (2009) Attenuation of Diabetic Nephropathy by Tocotrienol: Involvement of NFkB Signaling Pathway. Life Science, 84, 296-301. http://dx.doi.org/10.1016/j.lfs.2008.12.014
[36] Yousef, W.M., Omar, A.H., Ghanayeem, N.M., Waheed, M.M.A. and Morsey, M.D. (2005) Effect of Some Calcium Channel Blockers in Experimentally Induced Diabetic Nephropathy in Rats. Indocrinology, Metabolism and Diabetes Journal, 14, 39-49.
[37] Sener, G., Tugtepe, H., Yuksel, M., Cetinel, S., Gedik, N. and Yegen, B.C. (2006) Resveratrol Improves Ischemia/Reperfusion-Induced Oxidative Renal Injury in Rats. Archives of Medical Research, 37, 822-829. http://dx.doi.org/10.1016/j.arcmed.2006.04.003
[38] Tugtepe, H., Sener, G., Biyikli, N.K., Yuksel, M., Cetinel, S., Gedik, N. and Yegen, B.C. (2007) The Protective Effect of Oxytocin on Renal Ischemia/Reperfusion Injury in Rats. Regulatory Peptides, 140, 101-108. http://dx.doi.org/10.1016/j.regpep.2006.11.026
[39] Satoh, J., Yagihashi, S. and Toyota, T. (2003) The Possible Role of Tumor Necrosis Factor-Alpha in Diabetic Polyneuropathy. Experimental Diabesity Research, 4, 65-71.
http://dx.doi.org/10.1155/EDR.2003.65
[40] Bonventre, J.V. and Zuk, A. (2004) Ischemic Acute Renal Failure: An Inflammatory Disease? Kidney International, 66, 480-485. http://dx.doi.org/10.1111/j.1523-1755.2004.761_2.x
[41] Liu, R., Bal, H.S., Desta, T., Behl, Y. and Graves, D.T. (2006) Tumor Necrosis Factor-α Mediates Diabetes-Enhanced Apoptosis of Matrix-Producing Cells and Impairs Diabetic Healing. The American Journal of Clinical Pathology, 168, 757-764. http://dx.doi.org/10.2353/ajpath.2006.050907
[42] Yamagishi, S., Fukami, K., Ueda, S. and Okuda, S. (2007) Molecular Mechanisms of Diabetic Nephropathy and It’s Therapeutic Intervention. Current Drug Targets, 8, 952-959.
http://dx.doi.org/10.2174/138945007781386884
[43] Koike, N., Takamura, T. and Kaneko, S. (2007) Induction of Reactive Oxygen Species from Isolated Rat Glomeruli by Protein Kinase C Activation and TNF-α Stimulation, and Effects of a Phosphodiesterase Inhibitor. Life Science, 80, 1721-1728.
http://dx.doi.org/10.1016/j.lfs.2007.02.001
[44] Yeboah, M.M., Xue, X., Duan, B., Ochani, M., Tracey, K.J., Susin, M., et al. (2008) Cholinergic Agonists Attenuate Renal Ischemia-Reperfusion Injury in Rats. Kidney International, 74, 62-69.
http://dx.doi.org/10.1038/ki.2008.94
[45] Jitendra, D.V., Navin, R.S., Yagnik, S.B. and Nurudin, P.J. (2010) Exaggerated Liver Injury Induced by Renal Ischemia Reperfusion in Diabetes: Effect of Exenatide. The Saudi Journal of Gastroenterology, 16, 174-180. http://dx.doi.org/10.4103/1319-3767.65187
[46] Zheng, L., Du, Y., Miller, C., et al. (2007) Critical Role of Inducible Nitric Oxide Synthase in Degeneration of Retinal Capillaries in Mice with Streptozotocin-Induced Diabetes. Diabetologia, 50, 1987-1996.
[47] Yagmurca, M., Erdogan, H., Iraz, M., Songur, A., Ucar, M. and Fadillioglu, E. (2004) Caffeic Acid Phenethyl Ester as a Protective Agent against Doxorubicin Nephrotoxicity in Rats. Clinica Chimica Acta, 348, 27-34. http://dx.doi.org/10.1016/j.cccn.2004.03.035
[48] Matsuyama, M., Yoshimura, R., Hase, T., Kawahito, Y., Sano, H. and Nakatani, T. (2005) Study of Cyclooxygenase-2 in Renal Ischemia-Reperfusion Injury. Transplantation Proceeding, 37, 370-372. http://dx.doi.org/10.1016/j.transproceed.2004.12.246
[49] Moursi, M., Rising, C.L., Zelenock, G.B. and D’Alecy, L.G. (1997) Dextrose Administration Exacerbates Acute Renal Ischemic Damage in Anesthetized Dogs. Archives of Surgery, 122, 790-794. http://dx.doi.org/10.1001/archsurg.1987.01400190056011
[50] Ferreira, L., Teixeira-De-Lemos, E., Pinto, F., Parada, B., Mega, C., Vala, H., et al. (2010) Effects of Sitagliptin Treatment on Dysmetabolism, Inflammation, and Oxidative Stress in an Animal Model of Type 2 Diabetes (ZDF Rat). Mediators of Inflammation, 2010, Article ID: 592760.
http://dx.doi.org/10.1155/2010/592760
[51] Matsui, T., Nishino, Y., Takeuchi, M. and Yamagishi, S.I. (2011) Vildagliptin Blocks Vascular Injury in Thoracic Aorta of Diabetic Rats by Suppressing Advanced Glycation End Product-Receptor Axis. Pharmacological Research, 63, 383-388. http://dx.doi.org/10.1016/j.phrs.2011.02.003
[52] Li, L., El-Kholy, W., Rhodes, C.J. and Brubaker, P.L. (2005) Glucagon-Like Peptide-1 Protects Beta Cells from Cytokine-Induced Apoptosis and Necrosis: Role of Protein Kinase B. Diabetologia, 489, 1339-1349. http://dx.doi.org/10.1007/s00125-005-1787-2
[53] Zhang, X., Wang, Z., Huang, Y. and Wang, J. (2011) Effects of Chronic Administration of Alogliptin on the Development of Diabetes and β-Cell Function in High Fat Diet/Streptozotocin Diabetic Mice. Diabetes, Obesity and Metabolism, 13, 337-347.
http://dx.doi.org/10.1111/j.1463-1326.2010.01354.x

  
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