Research Journal of Pharmacy and Technology

Open Access Open Access  Restricted Access Subscription Access
Open Access Open Access Open Access  Restricted Access Restricted Access Subscription Access

A Compressive Review on Novel Molecular Target of Diabetic Nephropathy


Affiliations
1 Institute of Pharmaceutical Research, GLA University, 17 KM Stone, NH#2, Mathura - Delhi Road, P.O.: Chaumuhan Mathura – 281406,, India
     

   Subscribe/Renew Journal


Diabetic nephropathy (DN) is a leading cause of mortality and morbidity, decreases quality of life and shortened life expectancy. The renin angiotensin system is considered to be involved in most of the pathological processes that result in diabetic nephropathy. Various subsystems of RAAS contribute to the disease pathology. One of these involves angiotensin II (Ang II) which shows increased activity during diabetic nephropathy. Evidence indicates interaction between advanced glycation end products (AGEs), activated protein kinase C (PKC) and angiotensin II provoke the progression of DN. Inhibitors of angiotensin-converting enzyme (ACEIs), renin angiotensin aldosterone system (RAAS), AGEs, and PKC have been tested for slowing down the progression of DN. This review focuses on the latest published data dealing with the pathophysiology, stages of DN, pathogenesis, prevention and treatment of DN.

Keywords

Diabetic Nephropathy, Angiotensin, Nitric Oxide, Polyol Pathway, PKc.
Subscription Login to verify subscription
User
Notifications
Font Size


  • Ugochukwu NH, Babady NE, Cobourne M, et al. The effect of Gongronema latifolium extracts on serum lipid profile and oxidative stress in hepatocytes of diabetic rats. Journal of biosciences. 2003 Feb 1; 28(1):1-5.

  • Owu DU, Antai AB, Udofia KH, et al. Vitamin C improves basal metabolic rate and lipid profile in alloxan-induced diabetes mellitus in rat. J. Biosciences. 2006; 31: 575-579

  • Ahmed N. Alloxan diabetes-induced oxidative stress and impairment of oxidative defense system in rat brain: neuroprotective effects of cichorium intybus. Int J Diabetes & Metabolism. 2009; 17:105-9.

  • Soetikno V, Arozal W, Louisa M, et al. New insight into the molecular drug target of diabetic nephropathy. International journal of endocrinology. 2014; 2014.

  • Onozato ML, Tojo A. Role of NADPH oxidase in hypertension and diabetic nephropathy. Current Hypertension Reviews. 2005 Jan 1; 1(1):15-20.

  • Pan Y, Wang Y, Cai L, et al. Inhibition of high glucose‐induced inflammatory response and macrophage infiltration by a novel curcumin derivative prevents renal injury in diabetic rats. British journal of pharmacology. 2012 Jun; 166(3):1169-82.

  • Satirapoj B. Nephropathy in diabetes. In Diabetes 2013 (pp. 107-122). Springer, New York, NY.

  • Gnudi L, Viberti G, Raij L, et al. GLUT-1 over expression: link between hemodynamic and metabolic factors in glomerular injury? Hypertension. 2003 Jul 1; 42(1):19-24.

  • Singh N, Sharma P, Garg V, et al. Antioxidant therapy in diabetic nephropathy. Journal of Pharmacy Research. 2011 Nov; 4(11):4249-51.

  • Gnudi L. Cellular and molecular mechanisms of diabetic glomerulopathy. Nephrology Dialysis Transplantation. 2012 Jul 1; 27(7):2642-9.

  • Ha H, Hwang IA, Park JH, et al. Role of reactive oxygen species in the pathogenesis of diabetic nephropathy. Diabetes research and clinical practice. 2008 Nov 13; 82:S42-5.

  • Tavafi M. Diabetic nephropathy and antioxidants. Journal of nephropathology. 2013 Jan; 2(1):20.

  • Arya A, Yadav HN, Sharma PL. Involvement of vascular endothelial nitric oxide synthase in development of experimental diabetic nephropathy in rats. Molecular and cellular biochemistry. 2011 Aug 1; 354(1-2):57-66.

  • Dellamea BS, Leitão CB, Friedman R, et al. Nitric oxide system and diabetic nephropathy. Diabetology & metabolic syndrome. 2014 Dec 1; 6(1):17.

  • Hilgers KF, Veelken R. Type 2 diabetic nephropathy: never too early to treat? J Am Soc Nephrol. 2002; 16(3):574-75.

  • Rüster C, Wolf G. Renin-angiotensin-aldosterone system and progression of renal disease. Journal of the American Society of Nephrology. 2006 Nov 1; 17(11):2985-91.

  • El-Asrar AM. Role of inflammation in the pathogenesis of diabetic retinopathy. Middle East African journal of ophthalmology. 2012 Jan; 19(1):70.

  • Bonnet F, Candido R, Carey RM, et al. Renal expression of angiotensin receptors in long-term diabetes and the effects of angiotensin type 1 receptor blockade. Journal of hypertension. 2002 Aug 1; 20(8):1615-24.

  • Geraldes P, King GL. Activation of protein kinase C isoforms and its impact on diabetic complications. Circulation research. 2010 Apr 30; 106(8):1319-31.

  • El-Asrar AM. Role of inflammation in the pathogenesis of diabetic retinopathy. Middle East African journal of ophthalmology. 2012 Jan; 19(1):70.

  • Song J, Eyster KM, Kost Jr CK, et al. Involvement of protein kinase C-CPI-17 in androgen modulation of angiotensin II-renal vasoconstriction. Cardiovascular research. 2010 Feb 1; 85(3):614-21.

  • Geraldes P, King GL. Activation of protein kinase C isoforms and its impact on diabetic complications. Circulation research. 2010 Apr 30; 106(8):1319-31.

  • Peng F, Wu D, Gao B, Ingram AJ, Zhang B, Chorneyko K, McKenzie R, Krepinsky JC. RhoA/Rho-kinase contribute to the pathogenesis of diabetic renal disease. Diabetes. 2008 Jun 1; 57(6):1683-92.

  • Bach LA. Rho kinase inhibition: a new approach for treating diabetic nephropathy?. Diabetes. 2008 Mar 1; 57(3):532-33.

  • Kolavennu V, Zeng L, Peng H, et al. Targeting of RhoA/ROCK signaling ameliorates progression of diabetic nephropathy independent of glucose control. Diabetes. 2008 Mar 1; 57(3):714-23.

  • Peng F, Wu D, Gao B, et al. RhoA/Rho-kinase contribute to the pathogenesis of diabetic renal disease. Diabetes. 2008 Jun 1; 57(6):1683-92.

  • Suryavanshi SV, & Kulkarni Y A. NF-κβ: A Potential Target in the Management of Vascular Complications of Diabetes. Frontiers in pharmacology. 2017 8: 798.

  • Ahmed S, Mundhe N, Borgohain M. et al. Diosmin Modulates the NF-kB Signal Transduction Pathways and Downregulation of Various Oxidative Stress Markers in Alloxan-Induced Diabetic Nephropathy. Inflammation. 2016 39, 1783–1797. https://doi.org/10.1007/s10753-016-0413-4

  • Navarro-Gonzalez JF, Mora-Fernández C, De Fuentes MM, García-Pérez, J. Inflammatory molecules and pathways in the pathogenesis of diabetic nephropathy. Nat. Rev. Nephrol. 2011, 7, 327–340.

  • Luo C, Yang H, Tang C, et al. Kaempferol alleviates insulin resistance via hepatic IKK/NF-KB signal in type 2 diabetic rats. Int Immunopharmacol 2015; 28:744–50.

  • Liu T, Zhang L, Joo D, Sun SC. NF-κB signaling in inflammation. Signal transduction and targeted therapy. 2017 2, 17023.

  • Muhonen P, Holthofer H. Epigenetic and microRNA mediated regulation in diabetes. Nephrol Dial Transplant 2009; 24:1088–96

  • Moura J, Børsheim E, Carvalho E. The role of MicroRNAs in diabetic complications—special emphasis on wound healing. Genes 2014; 5:926–56.

  • McClelland AD, Herman-Edelstein M, Komers R, et al. MiR- 21 promotes renal fibrosis in diabetic nephropathy by targeting PTEN and SMAD7. Clin Sci 2015; 129:1237–49.

  • Zhang Z, Peng H, Chen J, et al. MicroRNA-21 protects from mesangial cell proliferation induced by diabetic nephropathy in db/db mice. FEBS Lett 2009; 583.

  • Wang Q, Wang Y, Minto AW, et al. MicroRNA-377 is up-regulated and can lead to increased fibronectin production in diabetic nephropathy. FASEB J 2008;22: 4126–35.

  • Long J, Wang Y, Wang W, Chang BH, Danesh FR. Identification of microRNA-93 as a novel regulator of vascular endothelial growth factor in hyperglycemic conditions. J Biol Chem 2010; 285:23457–65.

  • Wahlquist C, Jeong D, Rojas-Mun˜ oz A, et al. Inhibition of miR-25 improves cardiac contractility in the failing heart. Nature 2014; 508:531–538

  • Dey N, Das F, Mariappan MM, et al. MicroRNA-21 orchestrates high glucose-induced signals to TOR complex1, resulting in renal cell pathology in diabetes. J Biol Chem 2011; 286:25586–603. 40. Jones PA. Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nature Reviews Genetics. 2012 Jul;13(7):484-92.

  • Barrès R, Osler ME, Yan J, Rune A, Fritz T, Caidahl K, Krook A, Zierath JR. Non-CpG methylation of the PGC-1α promoter through DNMT3B controls mitochondrial density. Cell metabolism. 2009 Sep 2;10(3):189-98.

  • Tonna S, El-Osta A, Cooper ME, Tikellis C. Metabolic memory and diabetic nephropathy: potential role for epigenetic mechanisms. Nature Reviews Nephrology. 2010 Jun; 6(6):332-41.

  • Vivian EM, Rubinstein GB. Pharmacologic management of diabetic nephropathy. Clinical therapeutics. 2002 Nov 1; 24(11):1741-56.

  • Ravid M, Neumann L, Lishner M. Plasma lipids and the progression of nephropathy in diabetes mellitus type II: effect of ACE inhibitors. Kidney international. 1995 Mar 1; 47(3):907-10.

  • De P, Das G, Harley K, et al. Dual blockade of renin-angiotensin system in diabetic nephropathy: review of literature and local experience. The British Journal of Diabetes & Vascular Disease. 2006 Jan; 6(1):23-8.

  • Gan Z, Huang D, Jiang J, et al. Captopril alleviates hypertension-induced renal damage, inflammation, and NF-κB activation. Brazilian Journal of Medical and Biological Research. 2018; 51(11).

  • Mazerska M, Myśliwiec M. Telmisartan lowers albuminuria in type 2 diabetic patients treated with angiotensin enzyme inhibitors. Advances in Medical Sciences (De Gruyter Open). 2009 Jun 1; 54(1).

  • Shakya R, Goyal A, Semwal BC, et al. Role of Brain Angiotensin (1-7) In Chronic Hyperglycaemia Induced Nephropathy in Wistar Rats. Indian journal of Pharmaceutical education & Research. 2017 Jan 1; 51(1):83-91.

  • Simes BC, MacGregor GG. Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitors: A Clinician’s Guide. Diabetes, metabolic syndrome and obesity: targets and therapy. 2019; 12:2125.

  • Milder TY, Stocker SL, Abdel Shaheed C, et al. Combination therapy with an SGLT2 inhibitor as initial treatment for type 2 diabetes: a systematic review and meta-analysis. Journal of clinical medicine. 2019 Jan; 8(1):45.

  • Cefalu WT, Leiter LA, Yoon KH, et al. Efficacy and safety of canagliflozin versus glimepiride in patients with type 2 diabetes inadequately controlled with metformin (CANTATA-SU): 52-week results from a randomised, double-blind, phase 3 non-inferiority trial. The Lancet. 2013 Sep 14; 382(9896):941-50.

  • Zhang Z, Sun L, Wang Y, et al. Renoprotective role of the vitamin D receptor in diabetic nephropathy. Kidney international. 2008 Jan 2; 73(2):163-71.

  • Li YC. Vitamin D and diabetic nephropathy. Current diabetes reports. 2008 Dec 1; 8(6):464-9.

  • Bakris GL, Weir MR, Dequattro V, et al. Effects of an ACE inhibitor/calcium antagonist combination on proteinuria in diabetic nephropathy. Kidney international. 1998 Oct 1; 54(4):1283-9.

  • Schjoedt KJ, Rossing K, Juhl TR, et al. Beneficial impact of spironolactone in diabetic nephropathy. Kidney international. 2005 Dec 1; 68(6):2829-36.

  • Forbes JM, Thallas V, Thomas MC, et al. The breakdown of preexisting advanced glycation end products is associated with reduced renal fibrosis in experimental diabetes. The FASEB Journal. 2003 Sep; 17(12):1762-4.

  • Kelly DJ, Zhang Y, Hepper C, et al. Protein kinase C β inhibition attenuates the progression of experimental diabetic nephropathy in the presence of continued hypertension. Diabetes. 2003 Feb 1; 52(2):512-8.

  • Ko GJ, Kang YS, Han SY, et al. Pioglitazone attenuates diabetic nephropathy through an anti-inflammatory mechanism in type 2 diabetic rats. Nephrology Dialysis Transplantation. 2008 Sep 1; 23(9):2750-60.

  • Ohga S, Shikata K, Yozai K, et al. Thiazolidinedione ameliorates renal injury in experimental diabetic rats through anti- inflammatory effects mediated by inhibition of NF-κB activation. American Journal of Physiology-Renal Physiology. 2007 Apr; 292(4):F1141-50.

  • De Galan, B.E., Zoungas, S., Chalmers, J, et al. 2009. Cognitive function and risks of cardiovascular disease and hypoglycaemia in patients with type 2 diabetes: the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial. Diabetologia, 52(11), pp.2328-2336.

  • Bakris GL, Copley JB, Vicknair N, et al. Calcium channel blockers versus other antihypertensive therapies on progression of NIDDM associated nephropathy. Kidney international. 1996 Nov 1; 50(5):1641-50.

  • Bakris GL, Barnhill BW, Sadler R. Treatment of arterial hypertension in diabetic humans: importance of therapeutic selection. Kidney international. 1992 Apr 1; 41(4):912-9.

  • Hovind P, Rossing P, Tarnow L, et al. Remission of nephrotic-range albuminuria in type 1 diabetic patients. Diabetes Care. 2001 Nov 1; 24(11):1972-7.

  • Jones PA. Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nature Reviews Genetics. 2012 Jul; 13(7):484-92.

  • Barrès R, Osler ME, Yan J, Rune A, Fritz T, Caidahl K, Krook A, Zierath JR. Non-CpG methylation of the PGC-1α promoter through DNMT3B controls mitochondrial density. Cell metabolism. 2009 Sep 2; 10(3):189-98.

  • Gray SG, De Meyts P. Role of histone and transcription factor acetylation in diabetes pathogenesis. Diabetes/Metab Res Rev 2005; 21:416–33


Abstract Views: 160

PDF Views: 0




  • A Compressive Review on Novel Molecular Target of Diabetic Nephropathy

Abstract Views: 160  |  PDF Views: 0

Authors

Astha Jaiswal
Institute of Pharmaceutical Research, GLA University, 17 KM Stone, NH#2, Mathura - Delhi Road, P.O.: Chaumuhan Mathura – 281406,, India
Bhupesh Chandra Semwal
Institute of Pharmaceutical Research, GLA University, 17 KM Stone, NH#2, Mathura - Delhi Road, P.O.: Chaumuhan Mathura – 281406,, India
Sonia Singh
Institute of Pharmaceutical Research, GLA University, 17 KM Stone, NH#2, Mathura - Delhi Road, P.O.: Chaumuhan Mathura – 281406,, India

Abstract


Diabetic nephropathy (DN) is a leading cause of mortality and morbidity, decreases quality of life and shortened life expectancy. The renin angiotensin system is considered to be involved in most of the pathological processes that result in diabetic nephropathy. Various subsystems of RAAS contribute to the disease pathology. One of these involves angiotensin II (Ang II) which shows increased activity during diabetic nephropathy. Evidence indicates interaction between advanced glycation end products (AGEs), activated protein kinase C (PKC) and angiotensin II provoke the progression of DN. Inhibitors of angiotensin-converting enzyme (ACEIs), renin angiotensin aldosterone system (RAAS), AGEs, and PKC have been tested for slowing down the progression of DN. This review focuses on the latest published data dealing with the pathophysiology, stages of DN, pathogenesis, prevention and treatment of DN.

Keywords


Diabetic Nephropathy, Angiotensin, Nitric Oxide, Polyol Pathway, PKc.

References