Pioglitazone Treatment Enlarges Subcutaneous Adipocytes in Insulin-Resistant Patients

被引:33
作者
Koenen, Tim B. [3 ]
Tack, Cees J. [3 ]
Kroese, Jeanne Margot [1 ,3 ]
Hermus, Ad R. [1 ]
Sweep, Fred C. G. [4 ]
van der Laak, Jeroen [2 ]
Stalenhoef, Anton F. H. [3 ]
de Graaf, Jacqueline [3 ]
van Tits, Lambertus J. H. [3 ]
Stienstra, Rinke [3 ]
机构
[1] Radboud Univ Nijmegen, Med Ctr, Dept Endocrinol, NL-6500 HB Nijmegen, Netherlands
[2] Radboud Univ Nijmegen, Med Ctr, Dept Pathol, NL-6500 HB Nijmegen, Netherlands
[3] Radboud Univ Nijmegen, Med Ctr, Dept Gen Internal Med, NL-6500 HB Nijmegen, Netherlands
[4] Radboud Univ Nijmegen, Med Ctr, Dept Chem Endocrinol, NL-6500 HB Nijmegen, Netherlands
关键词
TYPE-2; DIABETIC-PATIENTS; ADIPOSE-TISSUE; CELL SIZE; FAT DISTRIBUTION; OBESITY; TROGLITAZONE; SENSITIVITY; EXPRESSION; HYPERPLASIA; EXERCISE;
D O I
10.1210/jc.2009-0517
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Context: Obesity-related insulin resistance is associated with an increase in adipocyte size. In rodent models, treatment with the insulin-sensitizers thiazolidinediones (TZDs) leads to the appearance of small, insulin-sensitive adipocytes. Whether such TZD-dependent morphological changes occur in adipose tissue of insulin-resistant patients is unclear. Objective: The objective of the study was to study the effects of treatment with the TZD pioglitazone on sc adipose tissue morphology and function in insulin-resistant subjects. Design: This was a placebo-controlled, randomized crossover study. Setting: The study was conducted at a university medical center. Patients: Twelve adult patients with congenital adrenal hyperplasia (CAH) characterized by insulin resistance were included in this study. Intervention: After a 4-wk run-in phase, patients were treated with pioglitazone (45 mg/d) followed by placebo, each for 16 wk or vice versa. Main Outcome Measures: After both placebo and pioglitazone treatment, insulin sensitivity was determined by hyperinsulinemic euglycemic clamp and abdominal sc adipose tissue was obtained to measure adipocyte cell surface and expression of genes involved in glucose uptake and inflammation. Results: Pioglitazone treatment significantly improved the insulin sensitivity index (placebo: 0.35 +/- 0.16 mu mol/kg . min per milliunit per liter; pioglitazone 0.53 +/- 0.16 mu mol/kg . min per milliunit per liter, P < 0.001) and increased mRNA expression levels of adiponectin and glucose transporter-4 in adipose tissue. The increase in insulin sensitivity was accompanied by a significant enlargement of the sc adipocyte cell surface (placebo: 2323 +/- 725 mu m(2); pioglitazone 2821 +/- 885 mu m(2), P = 0.03). Conclusions: In the human situation, treatment of insulin-resistant subjects with pioglitazone improves insulin sensitivity, whereas at the same time, sc adipocyte cell surface increases. (J Clin Endocrinol Metab 94: 4453-4457, 2009)
引用
收藏
页码:4453 / 4457
页数:5
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