A REVIEW ON THE ROLE OF PPARγ AGONISTS AND HYBRIDS IN TYPE 2 DIABETES AND CARDIOMYOPATHY.

Authors

  • Deepanwita Maji BIRLA INSTITUTE OF TECHNOLOGY
  • Subir Samanta

Abstract

Type 2 diabetes mellitus (DM) is a chronic multiple metabolic disorders characterized by increase in blood glucose level and accompanied with a
number of microvascular and macrovascular complications due to lifestyle factors, genetic factors related to impaired insulin secretion and insulin
resistance and environmental factors. Cardiovascular complications are one of the main causes responsible for 80% mortality rate in Type 2 diabetic
patients. Recently, amino acids and peptides are emerging as very good groups of antidiabetics as well as cardioprotective drugs, which may decrease
the symptoms of DM as well as take care of cardiovascular complications. Synthetic analogs of amylin and incretin mimetics are becoming ideal
adjuncts to diabetes therapy. To overcome the complications related to present day oral hypoglycemic agents which includes sulfonylureas, biguanide,
thiazolidinediones etc., This study has been done to review the role of peroxisome proliferator-activated receptor-γ agonists, amino acids and hybrid
compounds for activation of adenosine monophosphate-activated protein kinase receptors, which in turn plays important role in the treatment of
Type 2 diabetes and cardiomyopathy.

Keywords: Peroxisome proliferator-activated receptor-γ agonists, Thiazolidinediones, Hybrid compounds, Adenosine monophosphate-activated
protein kinase activation, Type 2 diabetes, Cardiomyopathy.

Downloads

Download data is not yet available.

Author Biography

Deepanwita Maji, BIRLA INSTITUTE OF TECHNOLOGY

Ph.D Scholar,Pharmaceutical Chemistry.

.Dept.of Pharmaceutical Sceiences andTechnology,BIT,MESRA,RANCHI 835215.JHARKHAND

References

Ramachandran A, Snehalatha C, Shetty AS, Nanditha A. Trends in prevalence of diabetes in Asian countries. World J Diabetes 2012;3(6):110-7.

Ramachandran A, Snehalatha C, Viswanathan V. Burden of type 2 diabetes and its complications – The Indian scenario. Curr Sci 2002;83:1471-6.

Sireesha K, Sailaja Rao P. Oxidative stress and diabetes: An overview. Asian J Pharm Clin Res 2015;8(1):15-9.

Blaschke F, Takata Y, Caglayan E, Law RE, Hsueh WA. Obesity, peroxisome proliferator-activated receptor, and atherosclerosis in type 2 diabetes. Arterioscler Thromb Vasc Biol 2006;26(1):28-40.

Diep QN, Benkirane K, Amiri F, Cohn JS, Endemann D, Schiffrin EL. PPAR alpha activator fenofibrate inhibits myocardial inflammation and fibrosis in angiotensin II-infused rats. J Mol Cell Cardiol 2004;36(2):295-304.

Molavi B, Chen J, Mehta JL. Cardioprotective effects of rosiglitazone are associated with selective overexpression of type 2 angiotensin receptors and inhibition of p42/44 MAPK. Am J Physiol Heart Circ Physiol 2006;291(2):H687-93.

Malik S, Upadhyaya PK, Miglani S. Thiazolidinediones : A plethro of biological load. Int J PharmTech Res 2011;3:62-75.

Molavi B, Rassouli N, Bagwe S, Rasouli N. A review of thiazolidinediones and metformin in the treatment of type 2 diabetes with focus on cardiovascular complications. Vasc Health Risk Manag 2007;3(6):967‑73.

Berger JP, Akiyama TE, Meinke PT. PPARs: Therapeutic targets for metabolic disease. Trends Pharmacol Sci 2005;26(5):244-51.

Roberts-Thomson SJ. Peroxisome proliferator-activated receptors in tumorigenesis: Targets of tumour promotion and treatment. Immunol Cell Biol 2000;78(4):436-41.

Plutzky J. Peroxisome proliferator - Activated receptors as therapeutic targets in inflammation. J Am Coll Cardiol 2003;42:8-10.

Balakumar P, Rose M, Ganti SS, Krishan P, Singh M. PPAR dual agonists: Are they opening Pandora’s Box? Pharmacol Res 2007;56(2):91-8.

Park CW, Zhang Y, Zhang X, Wu J, Chen L, Cha DR, et al. PPARalpha agonist fenofibrate improves diabetic nephropathy in db/db mice. Kidney Int 2006;69(9):1511-7.

Ravnskjaer K, Frigerio F, Boergesen M, Nielsen T, Maechler P, Mandrup S. PPARdelta is a fatty acid sensor that enhances mitochondrial oxidation in insulin-secreting cells and protects against fatty acid‑induced dysfunction. J Lipid Res 2010;51(6):1370-9.

Bastie C, Luquet S, Holst D, Jehl-Pietri C, Grimaldi PA. Alterations of peroxisome proliferator-activated receptor delta activity affect fatty acid-controlled adipose differentiation. J Biol Chem 2000;275(49):38768‑73.

Oliver WR Jr, Shenk JL, Snaith MR, Russell CS, Plunket KD, Bodkin NL, et al. A selective peroxisome proliferator-activated receptor delta agonist promotes reverse cholesterol transport. Proc Natl Acad Sci U S A 2001;98:5306-11.

Tenenbaum A, Motro M, Fisman EZ. Dual and pan-peroxisome proliferator-activated receptors (PPAR) co-agonism: The bezafibrate lessons. Cardiovasc Diabetol 2005;4:14.

Lee MY, Choi R, Kim HM, Cho EJ, Kim BH, Choi YS, et al. Peroxisome proliferator-activated receptor d agonist attenuates hepatic steatosis by anti-inflammatory mechanism. Exp Mol Med 2012;44(10):578-85.

Larsen TM, Toubro S, Astrup A. PPARgamma agonists in the treatment of type II diabetes: Is increased fatness commensurate with long-term efficacy? Int J Obes Relat Metab Disord 2003;27(2):147-61.

Garret JE, Melvin JP. A Fundamental and Clinical Text. Philadelphia: Lippincott Williams & Wilkin; 2004. p. 1130-48.

Sohda T, Mizuno K, Tawada H, Sugiyama Y, Fujita T, Kawamatsu Y. Studies on antidiabetic agents. I. Synthesis of 5-[4-(2-methyl-2-phenylpropoxy)-benzyl]thiazolidine-2,4-dione (AL-321) and related compounds. Chem Pharm Bull (Tokyo) 1982;30(10):3563-73.22. Fujita T, Sugiyama Y, Taketomi S, Sohda T, Kawamatsu Y, Iwatsuka H, et al. Reduction of insulin resistance in obese and/or diabetic animals by 5-[4-(1-methylcyclohexylmethoxy)benzyl]-thiazolidine-2,4-dione (ADD-3878, U-63,287, ciglitazone), a new antidiabetic agent. Diabetes 1983;32(9):804-10.

Fujiwara T, Yoshioka S, Yoshioka T, Ushiyama I, Horikoshi H. Characterization of new oral antidiabetic agent CS-045. Studies in KK and ob/ob mice and Zucker fatty rats. Diabetes 1988;37(11):1549-58.

Watkins PB, Whitcomb RW. Hepatic dysfunction associated with troglitazone. N Engl J Med 1998;338:916-7.

Oakes ND, Kennedy CJ, Jenkins AB, Laybutt DR, Chisholm DJ, Kraegen EW. A new antidiabetic agent, BRL 49653, reduces lipid availability and improves insulin action and glucoregulation in the rat. Diabetes 1994;43(10):1203-10.

Cantello BC, Cawthorne MA, Cottam GP, Duff PT, Haigh D, Hindley RM, et al. [[omega-(Heterocyclylamino)alkoxy]benzyl]-2,4-thiazolidinediones as potent antihyperglycemic agents. J Med Chem 1994;37(23):3977-85.

Lalloyer F, Staels B. Fibrates, glitazones, and peroxisome proliferator-activated receptors. Arterioscler Thromb Vasc Biol 2010;30(5):894-9.

Charbonnel B, Dormandy J, Erdmann E, Massi-Benedetti M, Skene A, PROactive Study Group. The prospective pioglitazone clinical trial in macrovascular events (PROactive): Can pioglitazone reduce cardiovascular events in diabetes? Study design and baseline characteristics of 5238 patients. Diabetes Care 2004;27(7):1647-53.

Adeghate E, Adem A, Hasan MY, Tekes K, Kalasz H. Medicinal chemistry and actions of dual and pan PPAR modulators. Open Med Chem J 2011;5 Suppl 2:93-8.

Tenenbaum A, Fisman EZ, Motro M. Metabolic syndrome and type 2 diabetes mellitus: Focus on peroxisome proliferator activated receptors (PPAR). Cardiovasc Diabetol 2003;2:4.

Diep QN, El Mabrouk M, Cohn JS, Endemann D, Amiri F, Virdis A, et al. Structure, endothelial function, cell growth, and inflammation in blood vessels of angiotensin II-infused rats: Role of peroxisome proliferator-activated receptor-gamma. Circulation 2002;105(19):2296‑302.

Villacorta L, Schopfer FJ, Zhang J, Freeman BA, Chen YE. PPARgamma and its ligands: Therapeutic implications in cardiovascular disease. Clin Sci (Lond) 2009;116(3):205-18.

Liang C, Ren Y, Tan H, He Z, Jiang Q, Wu J, et al. Rosiglitazone via upregulation of Akt/eNOS pathways attenuates dysfunction of endothelial progenitor cells, induced by advanced glycation end products. Br J Pharmacol 2009;158(8):1865-73.

Ceolotto G, Gallo A, Papparella I, Franco L, Murphy E, Iori E, et al. Rosiglitazone reduces glucose-induced oxidative stress mediated by NAD(P)H oxidase via AMPK-dependent mechanism. Arterioscler Thromb Vasc Biol 2007;27(12):2627-33.

Voulgari C, Papadogiannis D, Tentolouris N. Diabetic cardiomyopathy: From the pathophysiology of the cardiac myocytes to current diagnosis and management strategies. Vasc Health Risk Manag 2010 21;6:883‑903.

Gruzman A, Babai G, Sasson S. Adenosine monophosphate-activated protein kinase (AMPK) as a new target for antidiabetic drugs: A review on metabolic, pharmacological and chemical considerations. Rev Diabet Stud 2009;6(1):13-36.

Shirwany NA, Zou MH. AMPK in cardiovascular health and disease. Acta Pharmacol Sin 2010;31(9):1075-84.

Xie Z, Lau K, Eby B, Lozano P, He C, Pennington B, et al. Improvement of cardiac functions by chronic metformin treatment is associated with enhanced cardiac autophagy in diabetic OVE26 mice. Diabetes 2011;60(6):1770-8.

Poornima IG, Parikh P, Shannon RP. Diabetic cardiomyopathy: The search for a unifying hypothesis. Circ Res 2006;98(5):596-605.

Fang ZY, Prins JB, Marwick TH. Diabetic cardiomyopathy: Evidence, mechanisms, and therapeutic implications. Endocr Rev 2004;25(4):543‑67.

Nesto RW, Bell D, Bonow RO, Fonseca V, Grundy SM, Horton ES, et al. Thiazolidinedione use, fluid retention, and congestive heart failure: A consensus statement from the American Heart Association and American Diabetes Association. October 7, 2003. Circulation 2003;108(23):2941-8.

Wang J, Song Y, Wang Q, Kralik PM, Epstein PN. Causes and characteristics of diabetic cardiomyopathy. Rev Diabet Stud 2006;3(3):108-17.

Hayat SA, Patel B, Khattar RS, Malik RA. Diabetic cardiomyopathy: Mechanisms, diagnosis and treatment. Clin Sci (Lond) 2004;107(6):539‑57.

Fryer LG, Parbu-Patel A, Carling D. The Anti-diabetic drugs rosiglitazone and metformin stimulate AMP-activated protein kinase through distinct signaling pathways. J Biol Chem 2002;277(28):25226‑32.

Viollet B, Guigas B, Sanz Garcia N, Leclerc J, Foretz M, Andreelli F. Cellular and molecular mechanisms of metformin: An overview. Clin Sci (Lond) 2012;122(6):253-70.

Hemmalakshmi S, Devaki S, Priyan SK. In vivo antidiabetic potential of cyclea peltata in streptozotocin induced diabetic rats. Asian J Pharm Clin Res 2015;8(1):103-10.

Barrlett GC, Elmore TD. Amino Acids and Peptides. Cambridge: Cambridge University Press; 2004. p. 1-11.

Kim ED, Kim E, Lee JH, Hyun CK. Gly-Ala-Gly-Val-Gly-Tyr, a novel synthetic peptide, improves glucose transport and exerts beneficial lipid metabolic effects in 3T3-L1 adipocytes. Eur J Pharmacol 2011;650:487‑708.

Sulochana KN, Ge R. Developing antiangiogenic peptide drugs for angiogenesis-related diseases. Curr Pharm Des 2007;13(20):2074-86.

Ghosh R, Vaidehi T, Vilasrao JK. Novel peptides: An alternative approach for the treatment of diabetes mellitus. Curr Drug Ther 2007;2(3):196-204.

Setter SM, Neumiller JJ. Clinical focus on GLP-1 agonists in type 2 diabetes mellitus. US Pharm (Diabetes Suppl) 2011;36(5):10-5.

Nonoyama A, Laurence JS, Garriques L, Qi H, Le T, Middaugh CR. A biophysical characterization of the peptide drug pramlintide (AC137) using empirical phase diagrams. J Pharm Sci 2008;97(7):2552-67.

Mantzourani E, Laimou D, Matsoukas M, Tselios T. Peptides as therapeutic agents or drug leads for autoimmune, hormone dependent and cardiovascular diseases. Antiinflamm Antiallergy Agents Med Chem 2008;7:294-306.

Prabhakar C, Madhusudhan G, Sahadev K, Reddy CM, Sarma MR, Reddy GO, et al. Synthesis and biological activity of novel thiazolidinediones. Bioorg Med Chem Lett 1998;8(19):2725-30.

Chittiboyina AG, Venkatraman MS, Mizuno CS, Desai PV, Patny A, Benson SC, et al. Design and synthesis of the first generation of dithiolane thiazolidinedione- and phenylacetic acid-based PPARgamma agonists. J Med Chem 2006;49(14):4072-84.

Neogi P, Lakner FJ, Medicherla S, Cheng J, Dey D, Gowri M, et al. Synthesis and structure-activity relationship studies of cinnamic acid-based novel thiazolidinedione antihyperglycemic agents. Bioorg Med Chem 2003;11(18):4059-67.

Flora SJ. Structural, chemical and biological aspects of antioxidants for strategies against metal and metalloid exposure. Oxid Med Cell Longev 2009;2(4):191-206.

Kumar BR, Soni M, Kumar SS, Singh K, Patil M, Baig RB, et al. Synthesis, glucose uptake activity and structure-activity relationships of some novel glitazones incorporated with glycine, aromatic and alicyclic amine moieties via two carbon acyl linker. Eur J Med Chem 2011;46:835-44.

Jawale DV, Pratap UR, Rahuja N, Srivastava AK, Mane RA. Synthesis and antihyperglycemic evaluation of new 2,4-thiazolidinediones having biodynamic aryl sulfonylurea moieties. Bioorg Med Chem Lett 2012;22(1):436-9.

Mohler DL, Shen G, Dotse AK. Solution- and solid-phase synthesis of peptide-substituted thiazolidinediones as potential PPAR ligands. Bioorg Med Chem Lett 2000;10(20):2239-42.

Brunmair B, Staniek K, Gras F, Scharf N, Althaym A, Clara R, et al. Thiazolidinediones, like metformin, inhibit respiratory complex I: A common mechanism contributing to their antidiabetic actions? Diabetes 2004;53(4):1052-9.

Published

01-03-2015

How to Cite

Maji, D., and S. Samanta. “A REVIEW ON THE ROLE OF PPARγ AGONISTS AND HYBRIDS IN TYPE 2 DIABETES AND CARDIOMYOPATHY”. Asian Journal of Pharmaceutical and Clinical Research, vol. 8, no. 2, Mar. 2015, pp. 26-31, https://mail.innovareacademics.in/journals/index.php/ajpcr/article/view/3993.

Issue

Section

Review Article(s)