The Serine Protease Granzyme B as an Inflammatory Marker, in Relation to the Insulin Receptor Cleavage in Human Obesity and Type 2 Diabetes Mellitus
The Serine Protease Granzyme B as an Inflammatory Marker, in Relation to the Insulin Receptor Cleavage in Human Obesity and Type 2 Diabetes Mellitus
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DOI：
10.1089/jir.2013.0059
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发表时间：
2014-03-01
影响因子：
2.3
通讯作者：
Amin, Ashraf I.
中科院分区：
文献类型：
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作者：
El Mesallamy, Hala O.;Hamdy, Nadia M.;Amin, Ashraf I.
慢性炎症和胰岛素抵抗形成2型糖尿病（T2 DM）的标志。丝氨酸蛋白酶颗粒酶B（Gzm B）的循环水平增加在长期炎症期间被观察到，并且与几种慢性炎性疾病的发病机制有关。此外，在T2 DM中观察到胰岛素受体被未知蛋白酶切割，产生胰岛素受体α亚基（IR α）水平升高，并被认为是胰岛素抵抗的新机制。因此，GzmB和IR α之间可能存在关联。因此，本研究旨在探讨肥胖对T2 DM患者GzmB和IR α水平的影响。此外，我们的目标是确定GzmB是否通过其暗示的细胞外活性导致炎症和胰岛素抵抗。评估所有受试者与肥胖和T2 DM相关的人体测量和代谢参数。此外，空腹血浆胰岛素，GzmB，白细胞介素-1 β（IL-1 β），和IR α水平的酶联免疫吸附测定估计。与非糖尿病受试者相比，T2 DM患者的GzmB和IR α水平显著升高。此外，GzmB水平与肥胖和胰岛素抵抗、IL-1 β、IR α和其他代谢参数呈正相关。虽然多元线性回归分析显示，T2 DM和中心性肥胖都是GzmB的预测因素，但我们的研究结果揭示了GzmB在T2 DM中的可能作用。
Chronic inflammation and insulin resistance form hallmarks of type 2 diabetes mellitus (T2DM). An increased circulating level of the serine protease granzyme B (GzmB) is observed during prolonged inflammation and is implicated in the pathogenesis of several chronic inflammatory diseases. Moreover, insulin receptor cleavage by unknown proteases, yielding elevated levels of insulin receptor alpha-subunit (IR alpha), was observed in T2DM and was proposed as a new mechanism of insulin resistance. Therefore, a possible association between GzmB and IR alpha is suggested. Accordingly, this study was set to explore whether GzmB and IR alpha levels are altered in T2DM patients with the impact of obesity. Furthermore, we aimed to identify if GzmB contributes towards inflammation and insulin resistance through its suggested extracellular activities. All subjects were assessed for anthropometric and metabolic parameters related to obesity and T2DM. In addition, fasting plasma insulin, GzmB, interleukin-1 beta (IL-1 beta), and IR alpha levels were estimated by enzyme linked immunosorbent assay. Levels of GzmB and IR alpha were found to be significantly elevated in T2DM patients compared to nondiabetic subjects. In addition, GzmB levels were positively correlated with measures of obesity and insulin resistance, IL-1 beta, IR alpha, and other metabolic parameters. While multiple linear regression analysis revealed that both T2DM and central obesity were predicting factors for GzmB, our findings reveal a possible role of GzmB in T2DM.