REGIONAL VARIATION IN ADIPOSE-TISSUE INSULIN ACTION AND GLUT4 GLUCOSE-TRANSPORTER EXPRESSION IN SEVERELY OBESE PREMENOPAUSAL WOMEN

Insulin action and GLUT4 expression were examined in adipose tissue of severely obese premenopausal women undergoing gastrointestinal surger y. Fat samples were taken from three different anatomical regions: the subcutaneous abdominal site, the round ligament (deep abdominal prope ritoneal fat), and the greater omentum (deep abdominal intraperitoneal fat). The stimulatory effect of insulin on glucose transport and the ability of the hormone to inhibit lipolysis were determined in adipocy tes isolated from these three adipose depots. Insulin stimulated gluco se transport 2-3 times over basal rates in all adipocytes. However, ro und ligament adipose cells showed a significantly greater responsivene ss to insulin when compared to subcutaneous and omental adipocytes. Ro und ligament fat cells also displayed the greatest sensitivity and max imal antilipolytic response to insulin. We also investigated whether r egional differences in fat cell insulin-stimulated glucose transport w ere linked to a differential expression of the GLUT4 glucose transport er. GLUT4 protein content in total membranes was 5 and 2.2 times great er in round ligament adipose tissue than in subcutaneous and omental f at depots, respectively, Moreover, GLUT4 mRNA levels were 2.1 and 3 ti mes higher in round ligament than in subcutaneous or omental adipose t issues, respectively. Adipose tissue GLUT4 protein content was strongl y and negatively associated (r = -0.79 to -0.89, p < 0.01) with the wa ist-to-hip ratio but not with total adiposity. In conclusion, these re sults demonstrate the existence of site differences in adipose tissue insulin action in morbidly obese women. The greater insulin effect on glucose transport in round ligament adipocytes was associated with a h igher expression of GLUT4 when compared to subcutaneous abdominal and omental fat cells. Moreover, despite the regional variation in GLUT4 e xpression, an increased proportion of abdominal fat was found to be as sociated with lower levels of GLUT4 in all adipose regions investigate d.