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Decreased expression of insulin and increased expression of pancreatic transcription factor PDX-1 in islets in patients with liver cirrhosis: a comparative investigation using human autopsy specimens

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
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Abstract

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.

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Abbreviations

PDX-1:

Pancreatic duodenal homeobox-1

PCNA:

Proliferating cell nuclear antigen

BMI:

Body mass index

HbA1c:

Hemoglobin A1c

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Acknowledgments

This study was supported in part by a Grant-in-Aid for Young Scientists (B) (No. 19790643 to T.K.) and a Grant-in-Aid for Scientific Research (C) (No. 21590865 to M.S.) from the Ministry of Education, Culture, Sports, Science and Technology of Japan, by Health and Labour Sciences Research Grants for Research on Hepatitis from the Ministry of Health, Labour and Welfare of Japan, and by a Grant for Cancer Research from Fukuoka Cancer Society.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Japan

    Masahiro Sakata, Takumi Kawaguchi, Eitaro Taniguchi, Mitsuhiko Abe, Hironori Koga & Michio Sata

  2. Department of Diagnostic Pathology, Kurume University Hospital, Kurume, Japan

    Akihiko Kawahara, Jun Akiba, Tomoki Taira & Masayoshi Kage

  3. Department of Digestive Disease Information and Research, Kurume University School of Medicine, Kurume, Japan

    Takumi Kawaguchi & Michio Sata

  4. Department of Pathology, Kurume University School of Medicine, Kurume, Japan

    Jun Akiba

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  1. Masahiro Sakata
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  2. Akihiko Kawahara
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  3. Takumi Kawaguchi
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Correspondence to Masahiro Sakata.

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Sakata, M., Kawahara, A., Kawaguchi, T. et al. Decreased expression of insulin and increased expression of pancreatic transcription factor PDX-1 in islets in patients with liver cirrhosis: a comparative investigation using human autopsy specimens. J Gastroenterol 48, 277–285 (2013). https://doi.org/10.1007/s00535-012-0633-9

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  • DOI: https://doi.org/10.1007/s00535-012-0633-9

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