Pioglitazone Treatment Enlarges Subcutaneous Adipocytes in Insulin-Resistant Patients Export

@article{citeulike:6071629, abstract = {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 {micro}mol/kg {middle dot} min per milliunit per liter; pioglitazone 0.53 {+/-} 0.16 {micro}mol/kg {middle dot} 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 {micro}m2; pioglitazone 2821 {+/-} 885 {micro}m2, 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. 10.1210/jc.2009-0517}, author = {Koenen, Tim B. and Tack, Cees J. and Kroese, Jeanne M. and Hermus, Ad R. and Sweep, Fred C. G. and van der Laak, Jeroen and Stalenhoef, Anton F. H. and de Graaf, Jacqueline and van Tits, Lambertus J. H. and Stienstra, Rinke}, citeulike-article-id = {6071629}, citeulike-linkout-0 = {http://dx.doi.org/10.1210/jc.2009-0517}, citeulike-linkout-1 = {http://jcem.endojournals.org/content/94/11/4453.abstract}, citeulike-linkout-2 = {http://jcem.endojournals.org/content/94/11/4453.full.pdf}, citeulike-linkout-3 = {http://view.ncbi.nlm.nih.gov/pubmed/19820024}, citeulike-linkout-4 = {http://www.hubmed.org/display.cgi?uids=19820024}, day = {1}, doi = {10.1210/jc.2009-0517}, journal = {J Clin Endocrinol Metab}, keywords = {adipose-tissue, glitazone}, month = {November}, number = {11}, pages = {4453--4457}, posted-at = {2009-11-04 22:12:06}, priority = {2}, title = {Pioglitazone Treatment Enlarges Subcutaneous Adipocytes in Insulin-Resistant Patients}, url = {http://dx.doi.org/10.1210/jc.2009-0517}, volume = {94}, year = {2009} }

TY - JOUR ID - citeulike:6071629 L3 - citeulike-article-id:6071629 N2 - 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 {micro}mol/kg {middle dot} min per milliunit per liter; pioglitazone 0.53 {+/-} 0.16 {micro}mol/kg {middle dot} 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 {micro}m2; pioglitazone 2821 {+/-} 885 {micro}m2, 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. 10.1210/jc.2009-0517 IS - 11 JF - J Clin Endocrinol Metab EP - 4457 TI - Pioglitazone Treatment Enlarges Subcutaneous Adipocytes in Insulin-Resistant Patients VL - 94 SP - 4453 KW - adipose-tissue KW - glitazone AU - Koenen, Tim AU - Tack, Cees AU - Kroese, Jeanne AU - Hermus, Ad AU - Sweep, Fred AU - van der Laak, Jeroen AU - Stalenhoef, Anton AU - de Graaf, Jacqueline AU - van Tits, Lambertus AU - Stienstra, Rinke PY - 2009/11/01/ UR - http://dx.doi.org/10.1210/jc.2009-0517 ER -