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Expression of Ins1 and Ins2 genes in mouse fetal liver

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Abstract

A possible cure for diabetes is explored by using non-pancreatic cells such as fetal hepatocytes. The expression of insulin and transcription factors for insulin is investigated in mouse fetal liver. We detected mRNAs for insulin I (Ins1) and insulin II (Ins2) and proinsulin- and mature insulin-positive cells in mouse fetal liver by reverse transcription plus the polymerase chain reaction and immunohistochemistry. Glucagon, somatostatin and pancreatic polypeptide were not expressed throughout development. Mouse Ins2 and Ins1 promoters were transiently activated in mouse fetal hepatocytes of embryonic days 13.5 and 16.5, respectively. Pancreatic and duodenal homeobox 1 (Pdx1) mRNA was not expressed during development of the liver. In contrast, mRNAs and proteins of neurogenic differentiation (NeuroD)/β cell E-box transactivator 2 (Beta2) and v-maf musculoaponeurotic fibrosarcoma oncogene homolog (MafA) were almost simultaneously expressed with insulin genes in the liver. Ins2 and Ins1 promoters were activated in hepatoma cells by the transfection of the expression vector for NeuroD/Beta2 alone and by the combination of NeuroD/Beta2 and MafA, respectively. These results indicate that the expression of NeuroD/Beta2 and MafA is linked temporally with the transcription of Ins2 and Ins1 genes in mouse fetal liver and suggest the potential usage of fetal hepatocytes to make insulin-producing β cells by introducing transcription factors.

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Acknowledgments

We are grateful to Mr. Yuya Shichinohe for technical assistance and Mr. Brent Bell for critical reading of the manuscript. The present study is partial academic fulfillment for Thesis by S. M.-K. of Medical Science at Tohoku University.

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Authors and Affiliations

  1. Department of Advanced Biological Sciences for Regeneration (Kotobiken Medical Laboratories), Tohoku University Graduate School of Medicine, Sendai, 980-8575, Japan

    Shoko Murakami-Kawaguchi, Shin Takasawa, Tohru Onogawa & Koji Nata

  2. Department of Biochemistry, Nara Medical University, 840 Shijo-cho, Kashihara, 634-8521, Japan

    Shin Takasawa, Asako Itaya-Hironaka, Sumiyo Sakuramoto-Tsuchida, Akiyo Yamauchi, Hiroyo Ota & Maiko Takeda

  3. Division of Gastroenterological Surgery, Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, 980-8574, Japan

    Tohru Onogawa

  4. Department of Medical Biochemistry, School of Pharmacy, Iwate Medical University, Yahaba-cho, Shiwa-gun, Iwate, 028-3603, Japan

    Koji Nata

  5. Department of Anesthesiology, Tohoku University Graduate School of Medicine, Sendai, 980-8574, Japan

    Masato Kato

  6. Tohoku University, Sendai, 980-8577, Japan

    Hiroshi Okamoto

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  1. Shoko Murakami-Kawaguchi
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  2. Shin Takasawa
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Correspondence to Shin Takasawa.

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T.O. was the recipient of a fellowship from the Japan Society for Promotion of Science. This work was supported in part by Grants-in-Aid for Scientific Research from Ministry of Education, Culture, Sports, Science and Technology, Japan and from the Japan Science and Technology Agency (JST).

The authors declare no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

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Murakami-Kawaguchi, S., Takasawa, S., Onogawa, T. et al. Expression of Ins1 and Ins2 genes in mouse fetal liver. Cell Tissue Res 355, 303–314 (2014). https://doi.org/10.1007/s00441-013-1741-4

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