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      KCI등재 SCOPUS SCIE

      Refocusing Peroxisome Proliferator Activated Receptor-α: A New Insight for Therapeutic Roles in Diabetes

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      https://www.riss.kr/link?id=A104796474

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      다국어 초록 (Multilingual Abstract)

      Although glucose-lowering treatment shows some risk lowering effects in cardiovascular diseases, risks of macrovascular and microvascular complications have still remained, and development of new therapeutic strategies is needed. Recent data have shown that peroxisome proliferator activated receptor-α (PPAR-α) plays a pivotal role in the regulation of lipid homeostasis, fatty acid oxidation, cellular differentiation, and immune response such as inflammation or vascularization related to diabetic complication.
      This review will re-examine the metabolic role of PPAR-α, summarize data from clinical studies on the effect of PPAR-αagonist in diabetes, and will discuss the possible therapeutic role of PPAR-α activation.
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      Although glucose-lowering treatment shows some risk lowering effects in cardiovascular diseases, risks of macrovascular and microvascular complications have still remained, and development of new therapeutic strategies is needed. Recent data have show...

      Although glucose-lowering treatment shows some risk lowering effects in cardiovascular diseases, risks of macrovascular and microvascular complications have still remained, and development of new therapeutic strategies is needed. Recent data have shown that peroxisome proliferator activated receptor-α (PPAR-α) plays a pivotal role in the regulation of lipid homeostasis, fatty acid oxidation, cellular differentiation, and immune response such as inflammation or vascularization related to diabetic complication.
      This review will re-examine the metabolic role of PPAR-α, summarize data from clinical studies on the effect of PPAR-αagonist in diabetes, and will discuss the possible therapeutic role of PPAR-α activation.

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      참고문헌 (Reference)

      1 Long GG, "Urothelial carcinogenesis in the urinary bladder of rats treated with naveglitazar, a gamma-dominant PPAR alpha/gamma agonist: lack of evidence for urolithiasis as an inciting event" 36 : 218-231, 2008

      2 UK Prospective Diabetes Study Group, "Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38" 317 : 703-713, 1998

      3 Yki-Jarvinen H, "Thiazolidinediones" 351 : 1106-1118, 2004

      4 Staels B, "Therapeutic roles of peroxisome proliferator- activated receptor agonists" 54 : 2460-2470, 2005

      5 Cavender MA, "Therapeutic potential of aleglitazar, a new dual PPAR-α/γ agonist: implications for cardiovascular disease in patients with diabetes mellitus" 10 : 209-216, 2010

      6 Dressel U, "The peroxisome proliferator-activated receptor beta/delta agonist, GW501516, regulates the expression of genes involved in lipid catabolism and energy uncoupling in skeletal muscle cells" 17 : 2477-2493, 2003

      7 Friedland SN, "The cardiovascular effects of peroxisome proliferator-activated receptor agonists" 125 : 126-133, 2012

      8 송선옥, "The Risk of Bladder Cancer in Korean Diabetic Subjects Treated with Pioglitazone" 대한당뇨병학회 36 (36): 371-378, 2012

      9 Fruchart JC, "The Residual Risk Reduction Initiative: a call to action to reduce residual vascular risk in dyslipidaemic patient" 5 : 319-335, 2008

      10 Rutledge JC, "Role of triglyceride- rich lipoproteins in diabetic nephropathy" 6 : 361-370, 2010

      1 Long GG, "Urothelial carcinogenesis in the urinary bladder of rats treated with naveglitazar, a gamma-dominant PPAR alpha/gamma agonist: lack of evidence for urolithiasis as an inciting event" 36 : 218-231, 2008

      2 UK Prospective Diabetes Study Group, "Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38" 317 : 703-713, 1998

      3 Yki-Jarvinen H, "Thiazolidinediones" 351 : 1106-1118, 2004

      4 Staels B, "Therapeutic roles of peroxisome proliferator- activated receptor agonists" 54 : 2460-2470, 2005

      5 Cavender MA, "Therapeutic potential of aleglitazar, a new dual PPAR-α/γ agonist: implications for cardiovascular disease in patients with diabetes mellitus" 10 : 209-216, 2010

      6 Dressel U, "The peroxisome proliferator-activated receptor beta/delta agonist, GW501516, regulates the expression of genes involved in lipid catabolism and energy uncoupling in skeletal muscle cells" 17 : 2477-2493, 2003

      7 Friedland SN, "The cardiovascular effects of peroxisome proliferator-activated receptor agonists" 125 : 126-133, 2012

      8 송선옥, "The Risk of Bladder Cancer in Korean Diabetic Subjects Treated with Pioglitazone" 대한당뇨병학회 36 (36): 371-378, 2012

      9 Fruchart JC, "The Residual Risk Reduction Initiative: a call to action to reduce residual vascular risk in dyslipidaemic patient" 5 : 319-335, 2008

      10 Rutledge JC, "Role of triglyceride- rich lipoproteins in diabetic nephropathy" 6 : 361-370, 2010

      11 Frederiksen KS, "Prediction of PPAR-alpha ligand-mediated physiological changes using gene expression profiles" 45 : 592-560, 2004

      12 Ferwana M, "Pioglitazone and risk of bladder cancer: a meta-analysis of controlled studies" 30 : 1026-1032, 2013

      13 Hamren B, "Pharmacokinetic- pharmacodynamic assessment of the interrelationships between tesaglitazar exposure and renal function in patients with type 2 diabetes mellitus" 52 : 1317-1327, 2012

      14 Latruffe N, "Peroxisome-proliferator-activated receptors as physiological sensors of fatty acid metabolism: molecular regulation in peroxisomes" 29 (29): 305-309, 2001

      15 Wang YX, "Peroxisome-proliferator-activated receptor delta activates fat metabolism to prevent obesity" 113 : 159-170, 2003

      16 Brown JD, "Peroxisome proliferator-activated receptors as transcriptional nodal points and therapeutic targets" 115 : 518-533, 2007

      17 DiRenzo J, "Peroxisome proliferator-activated receptors and retinoic acid receptors differentially control the interactions of retinoid X receptor heterodimers with ligands, coactivators, and corepressors" 17 : 2166-2176, 1997

      18 Nakaya K, "Peroxisome proliferator-activated receptor-α activation promotes macrophage reverse cholesterol transport through a liver X receptor-dependent pathway" 31 : 1276-1282, 2011

      19 Rakhshandehroo M, "Peroxisome proliferator-activated receptor alpha target genes" 2010 : 612089-, 2010

      20 Berger JP, "PPARs: therapeutic targets for metabolic disease" 26 : 244-251, 2005

      21 Hiukka A, "PPARalpha: an emerging therapeutic target in diabetic microvascular damage" 6 : 454-463, 2010

      22 Park CW, "PPARalpha agonist fenofibrate improves diabetic nephropathy in db/db mice" 69 : 1511-1517, 2006

      23 Wilding JP, "PPAR agonists for the treatment of cardiovascular disease in patients with diabetes" 14 : 973-982, 2012

      24 Rosenson RS, "Modulating peroxisome proliferator-activated receptors for therapeutic benefit? Biology, clinical experience, and future prospects" 164 : 672-680, 2012

      25 Vamecq J, "Medical significance of peroxisome proliferator- activated receptors" 354 : 141-148, 1999

      26 Milionis HJ, "Management of hypertension and dyslipidaemia in patients presenting with hyperuricaemia: case histories" 16 : 164-170, 2000

      27 Kendall DM, "Improvement of glycemic control, triglycerides, and HDL cholesterol levels with muraglitazar, a dual (alpha/gamma) peroxisome proliferator-activated receptor activator, in patients with type 2 diabetes inadequately controlled with metformin monotherapy: a double-blind, randomized, pioglitazone-comparative study" 29 : 1016-1023, 2006

      28 Wannamethee SG, "Impact of diabetes on cardiovascular disease risk and allcause mortality in older men: influence of age at onset, diabetes duration, and established and novel risk factors" 171 : 404-410, 2011

      29 Frick MH, "Helsinki Heart Study: primary-prevention trial with gemfibrozil in middle-aged men with dyslipidemia. Safety of treatment, changes in risk factors, and incidence of coronary heart disease" 317 : 1237-1245, 1987

      30 Oleksiewicz MB, "Generalized cellular hypertrophy is induced by a dual-acting PPAR agonist in rat urinary bladder urothelium in vivo" 33 : 552-560, 2005

      31 Rubins HB, "Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group" 341 : 410-418, 1999

      32 Kouroumichakis I, "Fibrates: therapeutic potential for diabetic nephropathy?" 23 : 309-316, 2012

      33 Arakawa R, "Fenofibric acid, an active form of fenofibrate, increases apolipoprotein A-I-mediated high-density lipoprotein biogenesis by enhancing transcription of ATP-binding cassette transporter A1 gene in a liver X receptor-dependent manner" 25 : 1193-1197, 2005

      34 Tomizawa A, "Fenofibrate suppresses microvascular inflammation and apoptosis through adenosine monophosphate-activated protein kinase activation" 60 : 513-522, 2011

      35 Ansquer JC, "Fenofibrate reduces progression to microalbuminuria over 3 years in a placebo-controlled study in type 2 diabetes: results from the Diabetes Atherosclerosis Intervention Study (DAIS)" 45 : 485-493, 2005

      36 Hottelart C, "Fenofibrate increases creatininemia by increasing metabolic production of creatinine" 92 : 536-541, 2002

      37 Scott R, "Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study: baseline characteristics and short-term effects of fenofibrate [ISRCTN6478 3481]" 4 : 13-, 2005

      38 Keech A, "FIELD study investigators. Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial" 366 : 1849-1861, 2005

      39 Balakumar P, "Emerging role of PPAR ligands in the management of diabetic nephropathy" 60 : 170-173, 2009

      40 Ratner RE, "Efficacy, safety and tolerability of tesaglitazar when added to the therapeutic regimen of poorly controlled insulin-treated patients with type 2 diabetes" 4 : 214-221, 2007

      41 Cholesterol Treatment Trialists’ (CTT) Collaborators, "Efficacy of cholesterol-lowering therapy in 18,686 people with diabetes in 14 randomised trials of statins: a metaanalysis" 371 : 117-125, 2008

      42 ACCORD Study Group, "Effects of medical therapies on retinopathy progression in type 2 diabetes" 363 : 233-244, 2010

      43 Scott R, "Effects of fenofibrate treatment on cardiovascular disease risk in 9,795 individuals with type 2 diabetes and various components of the metabolic syndrome: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study" 32 : 493-498, 2009

      44 Davis TM, "Effects of fenofibrate on renal function in patients with type 2 diabetes mellitus: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study" 54 : 280-290, 2011

      45 Takahashi S, "Effects of combination treatment using anti-hyperuricaemic agents with fenofibrate and/or losartan on uric acid metabolism" 62 : 572-575, 2003

      46 ACCORD Study Group, "Effects of combination lipid therapy in type 2 diabetes mellitus" 362 : 1563-1574, 2010

      47 Henry RR, "Effect of the dual peroxisome proliferator-activated receptor-alpha/gamma agonist aleglitazar on risk of cardiovascular disease in patients with type 2 diabetes (SYNCHRONY): a phase II, randomised, dose-ranging study" 374 : 126-135, 2009

      48 Nissen SE, "Effect of muraglitazar on death and major adverse cardiovascular events in patients with type 2 diabetes mellitus" 294 : 2581-2586, 2005

      49 Keech AC, "Effect of fenofibrate on the need for laser treatment for diabetic retinopathy (FIELD study): a randomised controlled trial" 370 : 1687-1697, 2007

      50 Nagai T, "Effect of bezafibrate or pravastatin on serum lipid levels and albuminuria in NIDDM patients" 7 : 91-96, 2000

      51 Gaede P, "Effect of a multifactorial intervention on mortality in type 2 diabetes" 358 : 580-591, 2008

      52 Rosenson RS, "Does microvascular disease predict macrovascular events in type 2 diabetes?" 218 : 13-18, 2011

      53 Braissant O, "Differential expression of peroxisome proliferator-activated receptors (PPARs): tissue distribution of PPAR-alpha, -beta, and -gamma in the adult rat" 137 : 354-366, 1996

      54 Kanwar YS, "Diabetic nephropathy: mechanisms of renal disease progression" 233 : 4-11, 2008

      55 Bloomgarden ZT, "Cardiovascular disease in diabetes" 33 : e49-e54, 2010

      56 Smulders YM, "Can reduction in hypertriglyceridaemia slow progression of microalbuminuria in patients with non-insulin-dependent diabetes mellitus?" 27 : 997-1002, 1997

      57 Tenenbaum A, "Balanced pan-PPAR activator bezafibrate in combination with statin: comprehensive lipids control and diabetes prevention?" 11 : 140-, 2012

      58 Balakumar P, "Are PPAR alpha agonists a rational therapeutic strategy for preventing abnormalities of the diabetic kidney?" 65 : 430-436, 2012

      59 Balakumar P, "Ameliorative effect of combination of benfotiamine and fenofibrate in diabetes-induced vascular endothelial dysfunction and nephropathy in the rat" 320 : 149-162, 2009

      60 ACCORD Study Group, "Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial: design and methods" 99 (99): 21i-33i, 2007

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