Evidence of primary β-cell destruction by T-cells and β-cell differentiation from pancreatic ductal cells in diabetes associated with active autoimmune chronic pancreatitis

Shoichiro Tanaka, Tetsuro Kobayashi, Koji Nakanishi, Minoru Okubo, Toshio Murase, Masaji Hashimoto, Goro Watanabe, Hiroshi Matsushita, Yuzo Endo, Hideo Yoshizaki, Tomoo Kosuge, Michiie Sakamoto, Kazuo Takeuchi

研究成果: Article査読

52 被引用数 (Scopus)

抄録

OBJECTIVE - Diabetes associated with autoimmune chronic pancreatitis (ACP) is a subtype of diabetes that is responsive to corticosteroid treatment of progressive endocrine and exocrine dysfunction. However, little is known about pathological changes of islet and exocrine pancreas in ACP. RESEARCH DESIGN AND METHODS - We examined pancreatic specimens obtained on biopsy from four diabetic men with ACP (mean [range] age 62 years [48-78], duration of ACP 3 months [1-5], duration of diabetes 1 month [0-3]) morphologically, immunohistochemically, and morphometrically. RESULTS - The pancreatic specimens in all cases exhibited inflammatory cell infiltration surrounding ductal cells and extensive fibrosis. Some islets were infiltrated with mononuclear cells with disrupted β-cells. The subsets of T-cells infiltrated to the islets were mainly CD8+. Islet β-cell volume was decreased; the mean percentage area of β-cells in the islets in four cases with ACP were 16% (range 13-20) (P = 0.0015 vs. type 2 diabetic patients, 48% [27-73], n = 8; P = 0.0002 vs. nondiabetic control subjects, 58% [39-77], n = 7). Preserved ductal cells were surrounded predominantly by CD8+ or CD4+ T-cells. Some cytokeratin 19-positive ductal cells contained insulin and glucagon, representing upregulated differentiation of islet cells from ductal cells. Insulin promoter factor-1 (IPF-1) was hyperexpressed in insulin-containing ductal cells. CONCLUSIONS - Diabetes associated with ACP is caused by T-cell-mediated mechanisms primarily involving islet β-cells as well as pancreatic ductal cells. In ACP, ductal islet precursor cells were associated with IPF-1 hyperexpression, suggesting a critical role of IPF-1 on islet cell differentiation and eventual β-cell restoration.

本文言語English
ページ(範囲)1661-1667
ページ数7
ジャーナルDiabetes care
24
9
DOI
出版ステータスPublished - 2001
外部発表はい

ASJC Scopus subject areas

  • 内科学
  • 内分泌学、糖尿病および代謝内科学
  • 高度および特殊看護

フィンガープリント

「Evidence of primary β-cell destruction by T-cells and β-cell differentiation from pancreatic ductal cells in diabetes associated with active autoimmune chronic pancreatitis」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル