Laudes M, Oberhauser F, Schulte D M, Schilbach K, Freude S, Bilkovski R, Schulz O, Faust M, Krone W
Department of Internal Medicine II, University of Cologne, Germany.
Exp Clin Endocrinol Diabetes. 2010 Aug;118(8):473-7. doi: 10.1055/s-0030-1249014. Epub 2010 Mar 2.
Dipeptidyl-peptidase (DPP)-4, which catalizes the degradation of the insulinotropic incretin glucagon-like-peptide (GLP)-1, and the DPP-4 like enzyme attractin are involved in activation of T-lymphocytes and monocytes. Recently, it has been demonstrated, that the risk for certain infections is increased in type 2 diabetic patients under DPP-4 inhibitor treatment. The aim of the present study was to examine the expression of DPP-4 and attractin in circulating blood monocytes of obese and type 2 diabetic subjects. Monocytes were isolated by CD14-antibody based magnetic cell sorting from blood samples of 17 lean controls, 20 obese, non-diabetic subjects and 19 obese patients with type 2 diabetes. FACS analysis was performed to test purity of the cell preparations. Expression was measured by multiplex RT-PCR on RNA-level. DPP-4 and attractin were detectable in human circulating monocytes with attractin being expressed at higher levels compared to DPP-4. Both enzymes were significantly higher expressed in circulating blood monocytes of obese subjects compared to lean controls. In contrast, type 2 diabetes did not significantly affect expression levels. Finally, neither DPP-4 nor attractin expression was altered by sitagliptin or insulin treatment. In conclusion, our data demonstrate, that expressions of DPP-4 and attractin in circulating blood monocytes of human subjects are influenced by metabolic abnormalities with obesity being an important factor.
二肽基肽酶(DPP)-4可催化促胰岛素分泌的肠促胰岛素胰高血糖素样肽(GLP)-1的降解,而DPP-4样酶吸引素则参与T淋巴细胞和单核细胞的激活。最近有研究表明,2型糖尿病患者在接受DPP-4抑制剂治疗时,某些感染的风险会增加。本研究的目的是检测肥胖和2型糖尿病患者循环血单核细胞中DPP-4和吸引素的表达。通过基于CD14抗体的磁性细胞分选技术,从17名瘦对照者、20名肥胖非糖尿病患者和19名肥胖2型糖尿病患者的血样中分离出单核细胞。进行流式细胞术分析以检测细胞制剂的纯度。通过多重逆转录聚合酶链反应在RNA水平上测量表达。在人类循环单核细胞中可检测到DPP-4和吸引素,吸引素的表达水平高于DPP-4。与瘦对照者相比,肥胖受试者循环血单核细胞中这两种酶的表达均显著升高。相比之下,2型糖尿病并未显著影响表达水平。最后,西他列汀或胰岛素治疗均未改变DPP-4和吸引素的表达。总之,我们的数据表明,人类受试者循环血单核细胞中DPP-4和吸引素的表达受代谢异常影响,肥胖是一个重要因素。