Decreased expression of insulin and increasedexpression of pancreatic transcription factor PDX-1 in islets in patients with liver cirrhosis: a comparative investigation using human autopsy specimens.
Decreased expression of insulin and increasedexpression of pancreatic transcription factor PDX-1 in islets in patients with liver cirrhosis: a comparative investigation using human autopsy specimens.
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肝硬化患者胰岛中胰岛素表达降低和胰腺转录因子 PDX-1 表达增加：使用人体尸检标本的比较研究。
DOI：
10.1007/s00535-012-0633-9
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发表时间：
2013
期刊：
影响因子：
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通讯作者：
Sata M.
中科院分区：
文献类型：
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作者：
Sakata M;Kawahara A;Kawaguchi T;Akiba J;Taira T;Taniguchi E;Abe M;Koga H;Kage M;Sata M.
背景肝硬化（LC）患者的糖耐量异常（glucose intolerance）被称为肝源性糖尿病（hepatogenous diabetes），在某些方面被认为不同于2型糖尿病（type 2 diabetes，T2 DM）。肝脏疾病中的高胰岛素血症和/或胰岛素抵抗与肝癌的发生、肝癌的生长和不良预后相关。然而，病理生理过程中的胰岛是负责高胰岛素血症在LC仍然没有确切的了解。因此，我们研究了LC和T2 DM胰岛的组织病理学差异。方法35例尸检胰腺组织标本（对照组18例，T2 DM组6例，LC组11例）用于本研究。胰岛素，胰高血糖素，生长抑素，胰十二指肠同源框-1（PDX-1），增殖细胞核抗原（PCNA），Ki-67的表达进行了检查，采用免疫组化和定量图像analysis.ResultsIslet肥大和PCNA阳性细胞在胰岛中的显着增加，观察从LC病例的组织。LC组胰岛胰岛素阳性面积较对照组和T2 DM组明显减少（P= 0.001，P = 0.035），而PDX-1阳性面积较对照组明显增加（P= 0.001）。此外，胰腺内分泌细胞和PDX-1的核质易位的解体都被认为是在LC subjects.ConclusionsIn LC，胰岛进行肥大，并表现出矛盾的胰岛素和PDX-1的表达。在尸检的受试者中，胰岛素表达降低，而胰腺转录因子PDX-1的表达在LC中增加。这些结果指出了LC和T2 DM之间的重要区别。
BackgroundGlucose intolerance in patients with liver cirrhosis (LC), known as hepatogenous diabetes, is thought to be distinct from type 2 diabetes (T2DM) in some aspects. Hyperinsulinemia and/or insulin resistance in liver disease is associated with hepatocarcinogenesis, growth of hepatocellular carcinoma, and poor prognosis. However, the pathophysiological processes in islets that are responsible for hyperinsulinemia in LC are still not precisely known. Therefore, we investigated the histopathological differences in islets of Langerhans cells between LC and T2DM.MethodsA total of 35 human autopsy pancreatic tissue samples were used in this study (control,n= 18; T2DM,n= 6; LC,n= 11). The expression of insulin, glucagon, somatostatin, pancreatic duodenal homeobox-1 (PDX-1), proliferating cell nuclear antigen (PCNA), and Ki-67 was examined using immunohistochemistry and quantitated by image analysis.ResultsIslet hypertrophy and a significant increase in PCNA-positive cells in islets were observed in the tissues from LC cases. The insulin-positive areas in islets were significantly decreased in LC cases compared with control and T2DM cases (P= 0.001,P= 0.035, respectively), whereas the PDX-1-positive area was significantly increased in LC cases (P= 0.001) compared with the control. Furthermore, disorganization of pancreatic endocrine cells and nucleocytoplasmic translocation of PDX-1 were both seen in the LC subjects.ConclusionsIn LC, islets undergo hypertrophy and exhibit paradoxical expression of insulin and PDX-1. In the subjects autopsied, insulin expression was decreased, whereas expression of the pancreatic transcription factor PDX-1 was increased in LC. These results point to important distinctions between LC and T2DM.