EXPRESSION OF PEROXISOME-PROLIFERATOR ACTIVATED RECEPTORS- IN DIABETICS, OBESE AND NORMAL SUBJECTS
Abstract
Background: Current research in type 2 diabetes mellitus focuses on the role of Peroxisome-Proliferator Activated Receptors (PPARs) in the pathogenesis of the Insulin Resistance Syndrome (IRS), which are pre-diabetic lesion and the hallmark of fully developed type 2 diabetes mellitus. This study aims at identifying the abnormal status of the PPAR-g in adipose tissues of type 2 diabetes mellitus patients, when compared with matched normal controls. Methods: This cross-sectional study was conducted in Ayub Medical College, Abbottabad, from 2012 to 2014. Sample included three equal groups of patients. Group-1 with diagnosed type 2 diabetes mellitus, aged 40–65 years, acting as the test group, Group-2 included non-diabetic obese, and Group-3 with normal subjects. Transcription Factor Assay for Peroxisome Proliferator Activated Receptor Gamma (gamma PPAR) was done on ELISA Technique from Nuclear Extract procured from Adipose Tissue of the subjects. Results: Mean age of enrolled participants was 48.93 SD±6.52.years. Patients ranged between ages of 40 years to 67 years. The mean values of PPAR in normal, obese and diabetic group were 1.72 SD±0.28, 1.282 SE±0.18 and 1.283 SE±0.18 respectively. The difference in mean values of PPAR was significant p<0.05. Conclusion: The levels of PPAR-g in patients with type 2 Diabetes Mellitus and Obese cases are significantly lower than normal controls.References
McGarry JD. Dysregulation of fatty acid metabolism in the etiology of type 2 diabetes.(Banting Lecture 2001). Diabetes 2002;51(1):7–19.
Greenfield JR, Campbell LV. Insulin resistance and obesity. Clin Dermatol 2004;22(4):289–95.
Le Roith D, Zick Y. Recent advances in our understanding of insulin action and insulin resistance. Diabetes Care 2001;24(3):588–97.
Bloomgarden ZT. American Diabetes Association 60th Scientific Sessions, 2000 The Diabetic Foot. Diabetes Care 2001;24(5):946–51.
Zierath JR, Houseknecht KL, Gnudi L, Kahn BB. High-fat feeding impairs insulin-stimulated GLUT4 recruitment via an early insulin-signaling defect. Diabetes 1997;46(2):215–23.
Marx N, Sukhova G, Murphy C, Libby P, Plutzky J. Macrophages in human atheroma contain PPARγ: differentiation-dependent peroxisomal proliferator-activated receptor γ (PPARγ) expression and reduction of MMP-9 activity through PPARγ activation in mononuclear phagocytes in vitro. Am J Pathol 1998;153(1):17–23.
Hsueh WA, Jackson S, Law RE. Control of Vascular Cell Proliferation and Migration by PPAR-γ A new approach to the macrovascular complications of diabetes. Diabetes Care 2001;24(2):392–7.
Barroso I, Gurnell M, Crowley VE, Agostini M, Schwabe JW, Soos MA, et al. Dominant negative mutations in human PPARγ associated with severe insulin resistance, diabetes mellitus and hypertension. Nature 1999;402(6764):880–3.
Brun RP, Spiegelman BM. OBESITY AND THE ADIPOCYTE PPARγ and the molecular control of adipogenesis. Differentiation 1997;83:813–9.
Ducluzeau PH, Perretti N, Laville M, Andreelli F, Vega N, Riou JP, et al. Regulation by insulin of gene expression in human skeletal muscle and adipose tissue Evidence for specific defects in type 2 diabetes. Diabetes 2001;50(5):1134–42.
Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes estimates for the year 2000 and projections for 2030. Diabetes Care 2004;27(5):1047–53.
Sicree R, Shaw JE, Zimmet PZ, Tapp R. The global burden of diabetes. Diabetes Atlas 2003;2:15–71.
Unger RH, Zhou YT. Lipotoxicity of beta-cells in obesity and in other causes of fatty acid spillover. Diabetes 2001;50(suppl 1):S118–21.
Raji A, Seely EW, Arky RA, Simonson DC. Body fat distribution and insulin resistance in healthy Asian Indians and Caucasians. J Clin Endocrinol Metab 2001;86(11):5366–71.
McKeigue PM, Pierpoint T, Ferrie JE, Marmot MG. Relationship of glucose intolerance and hyperinsulinaemia to body fat pattern in south Asians and Europeans. Diabetologia 1992;35(8):785–91.
Ahmad LA, Crandall JP. Type 2 diabetes prevention: a review. Clin Diabetes 2010;28(2):53–9.
Pratley RE, Matfin G. Review: Pre-diabetes: clinical relevance and therapeutic approach. Br J Diabetes Vasc Dis 2007;7(3):120–9.
Buchanan TA, Xiang AH, Peters RK, Kjos SL, Marroquin A, Goico J, et al. Preservation of pancreatic β-cell function and prevention of type 2 diabetes by pharmacological treatment of insulin resistance in high-risk Hispanic women. Diabetes 2002;51(9):2796–803.
Fowler MJ. Microvascular and macrovascular complications of diabetes. Clin Diabetes 2008;26(2):77–82.
Berry D, Melkus GD. Epidemiologic perspectives of risk for developing diabetes and diabetes complications. Nur Clin North Am 2006;41(4):487–98.
Szanto A, Nagy L. The many faces of PPARγ: anti-inflammatory by any means?. Immunobiology. 2008;213(9):789–803.
Chawla A, Boisvert WA, Lee CH, Laffitte BA, Barak Y, Joseph SB, et al. A PPARγ-LXR-ABCA1 pathway in macrophages is involved in cholesterol efflux and atherogenesis. Mole Cell 2001;7(1):161–71.
McKenna NJ, O'Malley BW. Combinatorial control of gene expression by nuclear receptors and coregulators. Cell 2002;108(4):465–74.
MacDougald OA, Mandrup S. Adipogenesis: forces that tip the scales. Trends Endocrinol Metab 2002;13(1):5–11.
Barak Y, Nelson MC, Ong ES, Jones YZ, Ruiz-Lozano P, Chien KR, et al. PPARγ is required for placental, cardiac, and adipose tissue development. Mol Cell 1999;4(4):585–95.
Lehmann JM, Moore LB, Smith-Oliver TA, Wilkison WO, Willson TM, Kliewer SA. An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor γ (PPARγ). J Biol Chem 1995;270(22):12953–6.
Haliakon S, Doare L, Foufelle F, Kergoat M, Guerre-Millo M, Berthault MF, et al. Pioglitazone induces in vivo adipocyte differentiation in the obese Zucker fa/fa rat. Diabetes 1997;46(9):1393–9.
Zmyslowska A, Szadkowska A, Mianowska B, Pietrzak I, Wyka K, Mlynarski W. The Pro12Ala PPARg2 gene polymorphism involves residual C-peptide secretion and BMI in type 1 diabetes. Pediatr Endocrinol Diabetes Metab 2015;20(3):88–94.
Hashimoto T, Fujita T, Usuda N, Cook W, Qi C, Peters JM, et al. Peroxisomal and mitochondrial fatty acid β-oxidation in mice nullizygous for both peroxisome proliferator-activated receptor α and peroxisomal fatty acyl-CoA oxidase. Genotype correlation with fatty liver phenotype. J Biol Chem 1999;274(27):19228–36.
Kersten S, Seydoux J, Peters JM, Gonzalez FJ, Desvergne B, Wahli W. Peroxisome proliferator–activated receptor α mediates the adaptive response to fasting. J Clin Invest 1999;103(11):1489–98.
Aoyama T, Peters JM, Iritani N, Nakajima T, Furihata K, Hashimoto T, et al. Altered constitutive expression of fatty acid-metabolizing enzymes in mice lacking the peroxisome proliferator-activated receptor α (PPARα). J Biol Chem 1998;273(10):5678–84.
Laurin J. Clofibrate and other lipid-lowering drugs in the treatment of. Steatohepatitis NASH ASH 2001;121:188.
Park KS, Ciaraldi TP, Abrams-Carter L, Mudaliar S, Nikoulina SE, Henry RR. PPAR-γ gene expression is elevated in skeletal muscle of obese and type II diabetic subjects. Diabetes 1997;46(7):1230–4.
Bragt MC, Popeijus HE. Peroxisome proliferator-activated receptors and the metabolic syndrome. Physiol Behav 2008;94(2):187–97.
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