Molecular Analysis of db Gene-related Pancreatic .BETA. Cell Dysfunction; Evidence for a Compensatory Mechanism Inhibiting Development of Diabetes in the db Gene Heterozygote

• KANDA Yukiko

  Diabetes and Endocrine Division, Department of Internal Medicine, Kawasaki Medical School, Kurashiki, Japan

• SHIMODA Masashi

  Diabetes and Endocrine Division, Department of Internal Medicine, Kawasaki Medical School, Kurashiki, Japan

• TAWARAMOTO Kazuhito

  Diabetes and Endocrine Division, Department of Internal Medicine, Kawasaki Medical School, Kurashiki, Japan

• HAMAMOTO Sumiko

  Diabetes and Endocrine Division, Department of Internal Medicine, Kawasaki Medical School, Kurashiki, Japan

• TATSUMI Fuminori

  Diabetes and Endocrine Division, Department of Internal Medicine, Kawasaki Medical School, Kurashiki, Japan

• KAWASAKI Fumiko

  Diabetes and Endocrine Division, Department of Internal Medicine, Kawasaki Medical School, Kurashiki, Japan

• HASHIRAMOTO Mitsuru

  Diabetes and Endocrine Division, Department of Internal Medicine, Kawasaki Medical School, Kurashiki, Japan

• NAKASHIMA Koji

  Diabetes and Endocrine Division, Department of Internal Medicine, Kawasaki Medical School, Kurashiki, Japan

• MATSUKI Michihiro

  Diabetes and Endocrine Division, Department of Internal Medicine, Kawasaki Medical School, Kurashiki, Japan

• KAKU Kohei

  Diabetes and Endocrine Division, Department of Internal Medicine, Kawasaki Medical School, Kurashiki, Japan

抄録

The db gene homozygous, but not heterozygous, mice develop diabetes with severe β-cell damage. We investigated the molecular mechanism underlying db gene-associated pancreatic β-cell dysfunction. Islet morphology, β-cell function, and gene expression profiles specific for pancreatic islet cells were compared among db gene homozygous(db/db), heterozygous (db/m) and unrelated m/m mice. The β-cell ratio decreased in db/db mice with age, but not in non-diabetic db/m and m/m mice. The islet insulin content was lower, but the triglyceride content was higher in db/db than other mice. The islet cell specific gene expression profiles analyzed by laser capture microdissection method and morphological findings suggested an augmentation of β-cell apoptosis, oxidative stress and ER stress in db/db mice. Interestingly, insulin I and II, anti-apoptotic bcl-2, and proliferation promoting ERK-1 gene expressions were significantly upregulated in db/m mice. An impaired glucose tolerance was shown in m/m mice fed a high fat diet, but not in db/m mice, in which a higher insulin response and increased β-cell mass were observed. Expressions of insulin I and II, bcl-2, and ERK-1 gene were increased in db/m mice, but not in m/m fed a high fat diet. The present results strongly suggest that the db gene heterozygote, but not homozygote, acquires a compensatory mechanism suppressing β-cell apoptosis and augmenting the capacity of β-cell function.

収録刊行物

• Endocrine Journal

  Endocrine Journal 56 (8), 997-1008, 2009

  一般社団法人 日本内分泌学会

キーワード

• <I>db</I> gene heterozygote
• β cell dysfunction
• Cell proliferation
• Cell apoptosis
• Oxidative stress

詳細情報

• CRID: 1390282681275260032
• NII論文ID: 10026915747
• NII書誌ID: AA10901436
• DOI: 10.1507/endocrj.k09e-028
• ISSN: 13484540
• ISSN: 09188959
• Web Site: http://www.jstage.jst.go.jp/article/endocrj/56/8/56_K09E-028/_pdf
• 本文言語コード: en
• データソース種別:
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