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Human Pancreatic Alpha- to Beta-Cell Area Ratio Increases After Type 2 Diabetes Onset.

Human Pancreatic Alpha- to Beta-Cell Area Ratio Increases After Type 2 Diabetes Onset.
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Fujita Y, Kozawa J, Iwahashi H, Yoneda S, Uno S, Eguchi H, Nagano H, Imagawa A, Shimomura I,


Fujita Y, Kozawa J, Iwahashi H, Yoneda S, Uno S, Eguchi H, Nagano H, Imagawa A, Shimomura I, (click to view)

Fujita Y, Kozawa J, Iwahashi H, Yoneda S, Uno S, Eguchi H, Nagano H, Imagawa A, Shimomura I,

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Journal of diabetes investigation 2018 03 23() doi 10.1111/jdi.12841
Abstract
AIMS/INTRODUCTION
Pancreatic alpha-cell area and the alpha- to beta-cell area ratio (α/β) might be associated with glucose tolerance. The aim was to clarify how these histological parameters change as glucose tolerance deteriorates.

MATERIALS AND METHODS
We analyzed pancreatic tissues obtained from pancreatectomies in 43 patients. We evaluated the relationships between alpha-cell area or the α/β and various clinical parameters. Additionally, we analyzed alpha-cell proliferation and the expression patterns of various pancreatic transcription factors.

RESULTS
The α/β in individuals with longstanding (previously diagnosed) type 2 diabetes (0.36±0.12) was higher than that in those with normal glucose tolerance (0.18±0.10; p<0.01), impaired glucose tolerance (0.17±0.12; p<0.05), and newly diagnosed diabetes (0.17±0.12; p<0.05). In all subjects, HbA1c correlated with relative alpha-cell area (p=0.010). Diabetes duration (p=0.004), HbA1c (p<0.001), and plasma glucose levels (p=0.008) were significantly correlated with the α/β in single regression analyses, and diabetes duration was the only independent and significant determinant in stepwise multiple regression analyses (p=0.006). The alpha-cell Ki67-positive ratio in patients with HbA1c ≥6.5% was significantly higher than that in patients with HbA1c <6.5% (p=0.022). We identified beta-cells that expressed aristaless-related homeobox (ARX) and alpha-cells that did not express ARX at all glucose tolerance stages. ARX and NK homeobox 6.1 expression patterns varied in insulin and glucagon double-positive cells. CONCLUSIONS
The pancreatic α/β increases after type 2 diabetes onset and correlates with diabetes duration. This change might occur through alpha-cell proliferation and phenotypic changes in pancreatic endocrine cells. This article is protected by copyright. All rights reserved.

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