Thiazolidinediones and PPARγ agonists: time for a reassessment

被引：334

作者：

Cariou, Bertrand ^{[1
,2
,3
]}

Charbonnel, Bernard ^{[2
,3
]}

Staels, Bart ^{[4
,5
,6
]}

机构：

[1] INSERM, Unite Mixte Rech 1087, F-44000 Nantes, France

[2] Ctr Hosp Univ CHU Nantes, Clin Endocrinol, Inst Thorax, F-44000 Nantes, France

[3] Univ Nantes, Fac Med, F-44000 Nantes, France

[4] Univ Lille Nord France, F-59019 Lille, France

[5] Inst Pasteur, INSERM, Unite Mixte Rech 1011, F-59019 Lille, France

[6] Univ Lille 2, F-59019 Lille, France

来源：

TRENDS IN ENDOCRINOLOGY AND METABOLISM | 2012年 / 23卷 / 05期

关键词：

HEPATIC INSULIN SENSITIVITY; TYPE-2; DIABETES-MELLITUS; PIOGLITAZONE CLINICAL-TRIAL; FATTY LIVER IMPROVEMENT; INTIMA-MEDIA THICKNESS; MYOCARDIAL-INFARCTION; HEART-FAILURE; DOUBLE-BLIND; NONALCOHOLIC STEATOHEPATITIS; CARDIOVASCULAR-DISEASE;

D O I：

10.1016/j.tem.2012.03.001

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Thiazolidinediones (TZDs) are anti-diabetic drugs that act as insulin sensitizers and are used in the management of type 2 diabetes mellitus. TZDs, which are ligands for the transcription factor peroxisome proliferator-activated receptor PPAR gamma, have a wide spectrum of action, including modulation of glucose and lipid homeostasis, inflammation, atherosclerosis, bone remodeling and cell proliferation. Randomized clinical trials have demonstrated the efficacy and durability of the anti-hyperglycemic action of TZDs, and have suggested that the TZD pioglitazone also exerts cardioprotective action. However, the clinical use of TZDs is limited by the occurrence of several adverse events, including body-weight gain, congestive heart failure, bone fractures and possibly bladder cancer. Therefore, there is an unmet need for the development of new safer PPAR gamma-modulating drugs.

引用

页码：205 / 215

页数：11

共 100 条

[1] Non-DNA binding, dominant-negative, human PPARγ mutations cause lipodystrophic insulin resistance [J].

Agostini, Maura ;

Schoenmakers, Erik ;

Mitchell, Catherine ;

Szatmari, Istvan ;

Savage, David ;

Smith, Aaron ;

Rajanayagam, Odelia ;

Semple, Robert ;

Luan, Jian'an ;

Bath, Louise ;

Zalin, Anthony ;

Labib, Mourad ;

Kumar, Sudhesh ;

Simpson, Helen ;

Blom, Dirk ;

Marais, David ;

Schwabe, John ;

Barroso, Ines ;

Trembath, Richard ;

Wareham, Nicholas ;

Nagy, Laszlo ;

Gurnell, Mark ;

O'Rahilly, Stephen ;

Chatterjee, Krishna .

CELL METABOLISM, 2006, 4 (04) :303-311

[2] Effects of pioglitazone versus glipizide on body fat distribution, body water content, and hemodynamics in type 2 diabetes [J].

Basu, A ;

Jensen, MD ;

McCann, F ;

Mukhopadhyay, D ;

Joyner, MJ ;

Rizza, RA .

DIABETES CARE, 2006, 29 (03) :510-514

[3] A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis [J].

Belfort, Renata ;

Harrison, Stephen A. ;

Brown, Kenneth ;

Darland, Celia ;

Finch, Joan ;

Hardies, Jean ;

Balas, Bogdan ;

Gastaldelli, Amalia ;

Tio, Fermin ;

Pulcini, Joseph ;

Berria, Rachele ;

Ma, Jennie Z. ;

Dwivedi, Sunil ;

Havranek, Russell ;

Fincke, Chris ;

DeFronzo, Ralph ;

Bannayan, George A. ;

Schenker, Steven ;

Cusi, Kenneth .

NEW ENGLAND JOURNAL OF MEDICINE, 2006, 355 (22) :2297-2307

[4] Thiazolidinediones and fracture risk in patients with Type 2 diabetes [J].

Betteridge, D. J. .

DIABETIC MEDICINE, 2011, 28 (07) :759-771

[5]

Boardman MK, 2011, DIABETOLOGIA, V54, pS314

[6] Toxicological consequences of altered peroxisome proliferator-activated receptor γ (PPARγ) expression in the liver:: insights from models of obesity and type 2 diabetes [J].

Boelsterli, UA ;

Bedoucha, M .

BIOCHEMICAL PHARMACOLOGY, 2002, 63 (01) :1-10

[7] PPARγ activation primes human monocytes into alternative M2 macrophages with anti-inflammatory properties [J].

Bouhlel, M. Amine ;

Derudas, Bruno ;

Rigamonti, Elena ;

Dievart, Rebecca ;

Brozek, John ;

Haulon, Stephan ;

Zawadzki, Christophe ;

Jude, Brigitte ;

Torpier, Gerard ;

Marx, Nikolaus ;

Staels, Bart ;

Chinetti-Gbaguidi, Giulia .

CELL METABOLISM, 2007, 6 (02) :137-143

[8]

Caisse National d'Assurance Maladie, 2011, RISQ CANC VESS CHEZ

[9] Effects of the New Dual PPARα/δ Agonist GFT505 on Lipid and Glucose Homeostasis in Abdominally Obese Patients With Combined Dyslipidemia or Impaired Glucose Metabolism [J].

Cariou, Bertrand ;

Zair, Yassine ;

Staels, Bart ;

Bruckert, Eric .

DIABETES CARE, 2011, 34 (09) :2008-2014

[10]

Chao L., 2000, J CLIN INVEST, V101, P1354

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