Research Service, Phoenix VA Health Care System, Phoenix, AZ 85012, USA.
Biochem Biophys Res Commun. 2010 Nov 26;402(4):762-6. doi: 10.1016/j.bbrc.2010.10.104. Epub 2010 Oct 29.
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.
患有代谢综合征（胰岛素抵抗、葡萄糖耐量异常、血脂异常、高血压等）的受试者与正常人相比，腹部脂肪组织相对增加，肥胖也与胰岛素清除率降低有关。胰岛素的大部分清除是由于胰岛素降解酶（IDE）的作用，而 IDE 存在于所有组织中。由于肥胖时腹部脂肪增加，我们假设 IDE 可能在不同的脂肪库中发生改变。脂肪细胞从接受择期腹部手术的受试者的脂肪样本中分离出来。脂肪样本取自皮下（SQ）和内脏（VIS）部位。比较从 SQ 和 VIS 脂肪组织中分离出来的脂肪细胞中的胰岛素代谢。来自 VIS 部位的脂肪细胞降解的胰岛素比来自 SQ 脂肪组织的脂肪细胞多。组织蛋白酶 B 和 D 的抑制剂对胰岛素的降解没有影响，而 bacitracin，一种 IDE 的抑制剂，在 SQ 和 VIS 脂肪细胞中抑制降解约 33%。这些数据表明，胰岛素代谢在 VIS 中比在 SQ 脂肪组织中相对较高，可能是由于 IDE。
