Pioglitazone treatment enlarges subcutaneous adipocytes in insulin-resistant patients.
BACKGROUND
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.


METHODS
This was a placebo-controlled, randomized crossover study.


METHODS
The study was conducted at a university medical center.


METHODS
Twelve adult patients with congenital adrenal hyperplasia (CAH) characterized by insulin resistance were included in this study.


METHODS
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.


METHODS
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 micromol/kg . min per milliunit per liter; pioglitazone 0.53 +/- 0.16 micromol/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 microm(2); pioglitazone 2821 +/- 885 microm(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.
Koenen
Tim B
TB
Departments of General Internal Medicine, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, The Netherlands. t.koenen@aig.umcn.nl
Tack
Cees J
CJ
Kroese
Jeanne Margot
JM
Hermus
Ad R
AR
Sweep
Fred C G
FC
van der Laak
Jeroen
J
Stalenhoef
Anton F H
AF
de Graaf
Jacqueline
J
van Tits
Lambertus J H
LJ
Stienstra
Rinke
R
D017667:Adipocytes / Q000187:drug effects / Q000473:pathology*; D000312:Adrenal Hyperplasia, Congenital / Q000188:drug therapy* / Q000473:pathology; D000328:Adult; D018592:Cross-Over Studies; D015309:Glucose Clamp Technique / Q000379:methods; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007333:Insulin Resistance / Q000502:physiology*; D009765:Obesity / Q000473:pathology; D000077205:Pioglitazone; D010919:Placebos; D045162:Thiazolidinediones / Q000627:therapeutic use*
D007004:Hypoglycemic Agents; D010919:Placebos; D045162:Thiazolidinediones; D000077205:Pioglitazone