BACKGROUND: Glucose 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. METHODS: A 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. RESULTS: Islet 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. CONCLUSIONS: In 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.
BACKGROUND:Glucose 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. METHODS: A 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. RESULTS: Islet 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. CONCLUSIONS: In 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.
Authors: J C Brüning; M D Michael; J N Winnay; T Hayashi; D Hörsch; D Accili; L J Goodyear; C R Kahn Journal: Mol Cell Date: 1998-11 Impact factor: 17.970