| Autor: |
Stephen M. Twigg, Emilia Prakoso, Erika Cavanagh, Geoffrey W. McCaughan, Jim Raleigh, Anne-Sophie Veillard, Mark D. Gorrell, Belinda A. Brooks, Nicholas A. Shackel, Amany Zekry, Fiona M. Keane, Ana Julia Vieira de Ribeiro, Susan V. McLennan, Kathryn Williams, Yangmin Bu |
| Rok vydání: |
2014 |
| Předmět: |
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| Zdroj: |
Journal of Diabetes. 7:809-819 |
| ISSN: |
1753-0393 |
| DOI: |
10.1111/1753-0407.12237 |
| Popis: |
Background Intrahepatic expression of dipeptidyl peptidase-4 (DPP4), and circulating DPP4 (cDPP4) levels and its enzymatic activity, are increased in non-alcoholic fatty liver disease (NAFLD) and in type 2 diabetes mellitus and/or obesity. DPP4 has been implicated as a causative factor in NAFLD progression but few studies have examined associations between cDPP4 activity and NAFLD severity in humans. This study aimed to examine the relationship of cDPP4 activity with measures of liver disease severity in NAFLD in subjects with diabetes and/or obesity. Methods cDPP4 was measured in 106 individuals with type 2 diabetes who had transient elastography (Cohort 1) and 145 individuals with morbid obesity who had liver biopsy (Cohort 2). Both cohorts had caspase-cleaved keratin-18 (ccK18) measured as a marker of apoptosis. Results Natural log increases in cDPP4 activity were associated with increasing quartiles of ccK18 (Cohorts 1 and 2) and with median liver stiffness ≥10.3 kPa (Cohort 1) and significant fibrosis (F ≥ 2) on liver biopsy (Cohort 2). Conclusions In diabetes and/or obesity, cDPP4 activity is associated with current apoptosis and liver fibrosis. Given the pathogenic mechanisms by which DPP4 may progress NAFLD, measurement of cDPP4 activity may have utility to predict disease progression and DPP4 inhibition may improve liver histology over time. 摘要 背景： 在非酒精性脂肪性肝病（non-alcoholic fatty liver disease，NAFLD）、2型糖尿病和/或肥胖症患者中，二肽基肽酶-4（dipeptidyl peptidase-4，DPP4）的肝内表达、循环中的DPP4（circulating DPP4，cDPP4）水平以及它的酶活性都增加了。目前认为在NAFLD的进展过程中DPP4是一种致病因素，但是很少有研究调查人类cDPP4活性与NAFLD严重程度之间的关系。这项研究的目的是在糖尿病和/或肥胖症的受试者中调查cDPP4活性与测量到的NAFLD肝病严重程度之间的关系。 方法： 在106名接受瞬时弹性成像检查的2型糖尿病患者（队列1）以及145名接受肝脏活检的病态肥胖症患者（队列2）中测量cDPP4。对两个队列都测量了半胱天冬酶切割的角蛋白-18（caspase-cleaved keratin-18，ccK18）作为细胞凋亡指标。 结果： cDPP4活性的自然对数的增加与ccK18四分位数的增加相关（队列1与2），并且与肝脏硬度中位数≥ 10.3 kPa（队列1）以及肝脏活检有显著纤维化（F ≥ 2）（队列2）相关。 结论： 在糖尿病和/或肥胖症患者中，cDPP4活性与当前的肝细胞凋亡以及肝纤维化之间都有相关性。鉴于DPP4可能导致NAFLD进展的发病机制，测量cDPP4活性以预测疾病进展是一种实用的方法，并且随着时间的推移，抑制DPP4可以改善肝脏的组织学。 |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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