Subjects with the metabolic syndrome (insulin resistance glucose intolerance dyslipidemia hypertension etc) have a relative increase in abdominal fat tissue compared to normal individuals and obesity has also been shown to be associated with a decrease in insulin clearance The majority of the clearance of insulin is due to the action of insulin-degrading enzyme (IDE) and IDE is present throughout all tissues Since abdominal fat is increased in obesity we hypothesized that IDE may be altered in the different fat depots Adipocytes were isolated from fat samples obtained from subjects during elective abdominal surgery Fat samples were taken from subcutaneous (SQ) and visceral (VIS) sites Insulin metabolism was compared in adipocytes isolated from SQ and VIS fat tissue Adipocytes from the VIS site degraded more insulin that those from SQ fat tissue Inhibitors of cathepsins B and D has no effect on the degradation of insulin while bacitracin an inhibitor of IDE inhibited degradation by approx 33% in both SQ and VIS adipocytes These data show that insulin metabolism is relatively greater in VIS than in SQ fat tissue and potentially due to IDE Published by Elsevier Inc