Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 1661-1667 |
| Number of pages | 7 |
| Journal | Diabetes Care |
| Volume | 24 |
| Issue number | 9 |
| Publication status | Published - 2001 |
| Externally published | Yes |
Fingerprint
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Internal Medicine
Cite this
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. / Tanaka, Shoichiro; Kobayashi, Tetsuro; Nakanishi, Koji; Okubo, Minoru; Murase, Toshio; Hashimoto, Masaji; Watanabe, Goro; Matsushita, Hiroshi; Endo, Yuzo; Yoshizaki, Hideo; Kosuge, Tomoo; Sakamoto, Michiie; Takeuchi, Kazuo.
In: Diabetes Care, Vol. 24, No. 9, 2001, p. 1661-1667.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - 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
AU - Tanaka, Shoichiro
AU - Kobayashi, Tetsuro
AU - Nakanishi, Koji
AU - Okubo, Minoru
AU - Murase, Toshio
AU - Hashimoto, Masaji
AU - Watanabe, Goro
AU - Matsushita, Hiroshi
AU - Endo, Yuzo
AU - Yoshizaki, Hideo
AU - Kosuge, Tomoo
AU - Sakamoto, Michiie
AU - Takeuchi, Kazuo
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0035458871&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035458871&partnerID=8YFLogxK
M3 - Article
C2 - 11522716
AN - SCOPUS:0035458871
VL - 24
SP - 1661
EP - 1667
JO - Diabetes Care
JF - Diabetes Care
SN - 1935-5548
IS - 9
ER -