Human pancreatic α- to β-cell area ratio increases after type 2 diabetes onset

Yukari Fujita, Junji Kozawa, Hiromi Iwahashi, Sho Yoneda, Sae Uno, Hidetoshi Eguchi, Hiroaki Nagano, Akihisa Imagawa, Iichiro Shimomura

Research output: Contribution to journalArticle

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Abstract

Aims/Introduction: Pancreatic α-cell area and the α- to β-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 of 43 patients. We evaluated the relationships between α-cell area or the α/β and various clinical parameters. Additionally, we analyzed α-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 participants, glycated hemoglobin (HbA1c) correlated with relative α-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 α-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 β-cells that expressed aristaless-related homeobox and α-cells that did not express aristaless-related homeobox at all glucose tolerance stages. Aristaless-related homeobox 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 α-cell proliferation and phenotypic changes in pancreatic endocrine cells.

Original languageEnglish
Pages (from-to)1270-1282
Number of pages13
JournalJournal of Diabetes Investigation
Volume9
Issue number6
DOIs
Publication statusPublished - Nov 2018

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Type 2 Diabetes Mellitus
Homeobox Genes
Glucose
Regression Analysis
Cell Proliferation
Pancreatectomy
Glucose Intolerance
Endocrine Cells
Glycosylated Hemoglobin A
Glucagon
Transcription Factors
Insulin

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Fujita, Y., Kozawa, J., Iwahashi, H., Yoneda, S., Uno, S., Eguchi, H., ... Shimomura, I. (2018). Human pancreatic α- to β-cell area ratio increases after type 2 diabetes onset. Journal of Diabetes Investigation, 9(6), 1270-1282. https://doi.org/10.1111/jdi.12841

Human pancreatic α- to β-cell area ratio increases after type 2 diabetes onset. / Fujita, Yukari; Kozawa, Junji; Iwahashi, Hiromi; Yoneda, Sho; Uno, Sae; Eguchi, Hidetoshi; Nagano, Hiroaki; Imagawa, Akihisa; Shimomura, Iichiro.

In: Journal of Diabetes Investigation, Vol. 9, No. 6, 11.2018, p. 1270-1282.

Research output: Contribution to journalArticle

Fujita, Y, Kozawa, J, Iwahashi, H, Yoneda, S, Uno, S, Eguchi, H, Nagano, H, Imagawa, A & Shimomura, I 2018, 'Human pancreatic α- to β-cell area ratio increases after type 2 diabetes onset', Journal of Diabetes Investigation, vol. 9, no. 6, pp. 1270-1282. https://doi.org/10.1111/jdi.12841
Fujita, Yukari ; Kozawa, Junji ; Iwahashi, Hiromi ; Yoneda, Sho ; Uno, Sae ; Eguchi, Hidetoshi ; Nagano, Hiroaki ; Imagawa, Akihisa ; Shimomura, Iichiro. / Human pancreatic α- to β-cell area ratio increases after type 2 diabetes onset. In: Journal of Diabetes Investigation. 2018 ; Vol. 9, No. 6. pp. 1270-1282.
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AU - Fujita, Yukari

AU - Kozawa, Junji

AU - Iwahashi, Hiromi

AU - Yoneda, Sho

AU - Uno, Sae

AU - Eguchi, Hidetoshi

AU - Nagano, Hiroaki

AU - Imagawa, Akihisa

AU - Shimomura, Iichiro

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N2 - Aims/Introduction: Pancreatic α-cell area and the α- to β-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 of 43 patients. We evaluated the relationships between α-cell area or the α/β and various clinical parameters. Additionally, we analyzed α-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 participants, glycated hemoglobin (HbA1c) correlated with relative α-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 α-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 β-cells that expressed aristaless-related homeobox and α-cells that did not express aristaless-related homeobox at all glucose tolerance stages. Aristaless-related homeobox 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 α-cell proliferation and phenotypic changes in pancreatic endocrine cells.

AB - Aims/Introduction: Pancreatic α-cell area and the α- to β-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 of 43 patients. We evaluated the relationships between α-cell area or the α/β and various clinical parameters. Additionally, we analyzed α-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 participants, glycated hemoglobin (HbA1c) correlated with relative α-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 α-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 β-cells that expressed aristaless-related homeobox and α-cells that did not express aristaless-related homeobox at all glucose tolerance stages. Aristaless-related homeobox 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 α-cell proliferation and phenotypic changes in pancreatic endocrine cells.

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