Increased vimentin in human α- and β-cells in type 2 diabetes

Maaike M Roefs; Françoise Carlotti; Katherine Jones; Hannah Wills; Alexander Hamilton; Michael Verschoor; Joanna M Williams Durkin; Laura Garcia-Perez; Melissa F Brereton; Laura McCulloch; Marten A Engelse; Paul R V Johnson; Barbara C Hansen; Kevin Docherty; Eelco J P de Koning; Anne Clark

doi:10.1530/JOE-16-0588

Increased vimentin in human α- and β-cells in type 2 diabetes

Maaike M Roefs, Françoise Carlotti, Katherine Jones, Hannah Wills, Alexander Hamilton, Michael Verschoor, Joanna M Williams Durkin, Laura Garcia-Perez, Melissa F Brereton, Laura McCulloch, Marten A Engelse, Paul R V Johnson, Barbara C Hansen, Kevin Docherty, Eelco J P de Koning, Anne Clark

Hubrecht Institute

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

27 Citations (Scopus)

Abstract

Type 2 diabetes (T2DM) is associated with pancreatic islet dysfunction. Loss of β-cell identity has been implicated via dedifferentiation or conversion to other pancreatic endocrine cell types. How these transitions contribute to the onset and progression of T2DM in vivo is unknown. The aims of this study were to determine the degree of epithelial-to-mesenchymal transition occurring in α and β cells in vivo and to relate this to diabetes-associated (patho)physiological conditions. The proportion of islet cells expressing the mesenchymal marker vimentin was determined by immunohistochemistry and quantitative morphometry in specimens of pancreas from human donors with T2DM (n = 28) and without diabetes (ND, n = 38) and in non-human primates at different stages of the diabetic syndrome: normoglycaemic (ND, n = 4), obese, hyperinsulinaemic (HI, n = 4) and hyperglycaemic (DM, n = 8). Vimentin co-localised more frequently with glucagon (α-cells) than with insulin (β-cells) in the human ND group (1.43% total α-cells, 0.98% total β-cells, median; P < 0.05); these proportions were higher in T2DM than ND (median 4.53% α-, 2.53% β-cells; P < 0.05). Vimentin-positive β-cells were not apoptotic, had reduced expression of Nkx6.1 and Pdx1, and were not associated with islet amyloidosis or with bihormonal expression (insulin + glucagon). In non-human primates, vimentin-positive β-cell proportion was larger in the diabetic than the ND group (6.85 vs 0.50%, medians respectively, P < 0.05), but was similar in ND and HI groups. In conclusion, islet cell expression of vimentin indicates a degree of plasticity and dedifferentiation with potential loss of cellular identity in diabetes. This could contribute to α- and β-cell dysfunction in T2DM.

Original language	English
Pages (from-to)	217-227
Number of pages	11
Journal	The Journal of endocrinology
Volume	233
Issue number	3
DOIs	https://doi.org/10.1530/JOE-16-0588
Publication status	Published - Jun 2017

Keywords

Animals
Case-Control Studies
Cells, Cultured
Diabetes Mellitus, Type 2
Glucagon-Secreting Cells
Humans
Hyperinsulinism
Insulin-Secreting Cells
Macaca fascicularis
Macaca mulatta
Vimentin
Journal Article

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10.1530/JOE-16-0588

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Roefs, M. M., Carlotti, F., Jones, K., Wills, H., Hamilton, A., Verschoor, M., Durkin, J. M. W., Garcia-Perez, L., Brereton, M. F., McCulloch, L., Engelse, M. A., Johnson, P. R. V., Hansen, B. C., Docherty, K., de Koning, E. J. P., & Clark, A. (2017). Increased vimentin in human α- and β-cells in type 2 diabetes. The Journal of endocrinology, 233(3), 217-227. https://doi.org/10.1530/JOE-16-0588

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title = "Increased vimentin in human α- and β-cells in type 2 diabetes",

abstract = "Type 2 diabetes (T2DM) is associated with pancreatic islet dysfunction. Loss of β-cell identity has been implicated via dedifferentiation or conversion to other pancreatic endocrine cell types. How these transitions contribute to the onset and progression of T2DM in vivo is unknown. The aims of this study were to determine the degree of epithelial-to-mesenchymal transition occurring in α and β cells in vivo and to relate this to diabetes-associated (patho)physiological conditions. The proportion of islet cells expressing the mesenchymal marker vimentin was determined by immunohistochemistry and quantitative morphometry in specimens of pancreas from human donors with T2DM (n = 28) and without diabetes (ND, n = 38) and in non-human primates at different stages of the diabetic syndrome: normoglycaemic (ND, n = 4), obese, hyperinsulinaemic (HI, n = 4) and hyperglycaemic (DM, n = 8). Vimentin co-localised more frequently with glucagon (α-cells) than with insulin (β-cells) in the human ND group (1.43% total α-cells, 0.98% total β-cells, median; P < 0.05); these proportions were higher in T2DM than ND (median 4.53% α-, 2.53% β-cells; P < 0.05). Vimentin-positive β-cells were not apoptotic, had reduced expression of Nkx6.1 and Pdx1, and were not associated with islet amyloidosis or with bihormonal expression (insulin + glucagon). In non-human primates, vimentin-positive β-cell proportion was larger in the diabetic than the ND group (6.85 vs 0.50%, medians respectively, P < 0.05), but was similar in ND and HI groups. In conclusion, islet cell expression of vimentin indicates a degree of plasticity and dedifferentiation with potential loss of cellular identity in diabetes. This could contribute to α- and β-cell dysfunction in T2DM.",

keywords = "Animals, Case-Control Studies, Cells, Cultured, Diabetes Mellitus, Type 2, Glucagon-Secreting Cells, Humans, Hyperinsulinism, Insulin-Secreting Cells, Macaca fascicularis, Macaca mulatta, Vimentin, Journal Article",

author = "Roefs, {Maaike M} and Fran{\c c}oise Carlotti and Katherine Jones and Hannah Wills and Alexander Hamilton and Michael Verschoor and Durkin, {Joanna M Williams} and Laura Garcia-Perez and Brereton, {Melissa F} and Laura McCulloch and Engelse, {Marten A} and Johnson, {Paul R V} and Hansen, {Barbara C} and Kevin Docherty and {de Koning}, {Eelco J P} and Anne Clark",

note = "{\textcopyright} 2017 Society for Endocrinology.",

year = "2017",

month = jun,

doi = "10.1530/JOE-16-0588",

language = "English",

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pages = "217--227",

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issn = "0022-0795",

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Roefs, MM, Carlotti, F, Jones, K, Wills, H, Hamilton, A, Verschoor, M, Durkin, JMW, Garcia-Perez, L, Brereton, MF, McCulloch, L, Engelse, MA, Johnson, PRV, Hansen, BC, Docherty, K, de Koning, EJP & Clark, A 2017, 'Increased vimentin in human α- and β-cells in type 2 diabetes', The Journal of endocrinology, vol. 233, no. 3, pp. 217-227. https://doi.org/10.1530/JOE-16-0588

TY - JOUR

T1 - Increased vimentin in human α- and β-cells in type 2 diabetes

AU - Roefs, Maaike M

AU - Carlotti, Françoise

AU - Jones, Katherine

AU - Wills, Hannah

AU - Hamilton, Alexander

AU - Verschoor, Michael

AU - Durkin, Joanna M Williams

AU - Garcia-Perez, Laura

AU - Brereton, Melissa F

AU - McCulloch, Laura

AU - Engelse, Marten A

AU - Johnson, Paul R V

AU - Hansen, Barbara C

AU - Docherty, Kevin

AU - de Koning, Eelco J P

AU - Clark, Anne

PY - 2017/6

Y1 - 2017/6

N2 - Type 2 diabetes (T2DM) is associated with pancreatic islet dysfunction. Loss of β-cell identity has been implicated via dedifferentiation or conversion to other pancreatic endocrine cell types. How these transitions contribute to the onset and progression of T2DM in vivo is unknown. The aims of this study were to determine the degree of epithelial-to-mesenchymal transition occurring in α and β cells in vivo and to relate this to diabetes-associated (patho)physiological conditions. The proportion of islet cells expressing the mesenchymal marker vimentin was determined by immunohistochemistry and quantitative morphometry in specimens of pancreas from human donors with T2DM (n = 28) and without diabetes (ND, n = 38) and in non-human primates at different stages of the diabetic syndrome: normoglycaemic (ND, n = 4), obese, hyperinsulinaemic (HI, n = 4) and hyperglycaemic (DM, n = 8). Vimentin co-localised more frequently with glucagon (α-cells) than with insulin (β-cells) in the human ND group (1.43% total α-cells, 0.98% total β-cells, median; P < 0.05); these proportions were higher in T2DM than ND (median 4.53% α-, 2.53% β-cells; P < 0.05). Vimentin-positive β-cells were not apoptotic, had reduced expression of Nkx6.1 and Pdx1, and were not associated with islet amyloidosis or with bihormonal expression (insulin + glucagon). In non-human primates, vimentin-positive β-cell proportion was larger in the diabetic than the ND group (6.85 vs 0.50%, medians respectively, P < 0.05), but was similar in ND and HI groups. In conclusion, islet cell expression of vimentin indicates a degree of plasticity and dedifferentiation with potential loss of cellular identity in diabetes. This could contribute to α- and β-cell dysfunction in T2DM.

AB - Type 2 diabetes (T2DM) is associated with pancreatic islet dysfunction. Loss of β-cell identity has been implicated via dedifferentiation or conversion to other pancreatic endocrine cell types. How these transitions contribute to the onset and progression of T2DM in vivo is unknown. The aims of this study were to determine the degree of epithelial-to-mesenchymal transition occurring in α and β cells in vivo and to relate this to diabetes-associated (patho)physiological conditions. The proportion of islet cells expressing the mesenchymal marker vimentin was determined by immunohistochemistry and quantitative morphometry in specimens of pancreas from human donors with T2DM (n = 28) and without diabetes (ND, n = 38) and in non-human primates at different stages of the diabetic syndrome: normoglycaemic (ND, n = 4), obese, hyperinsulinaemic (HI, n = 4) and hyperglycaemic (DM, n = 8). Vimentin co-localised more frequently with glucagon (α-cells) than with insulin (β-cells) in the human ND group (1.43% total α-cells, 0.98% total β-cells, median; P < 0.05); these proportions were higher in T2DM than ND (median 4.53% α-, 2.53% β-cells; P < 0.05). Vimentin-positive β-cells were not apoptotic, had reduced expression of Nkx6.1 and Pdx1, and were not associated with islet amyloidosis or with bihormonal expression (insulin + glucagon). In non-human primates, vimentin-positive β-cell proportion was larger in the diabetic than the ND group (6.85 vs 0.50%, medians respectively, P < 0.05), but was similar in ND and HI groups. In conclusion, islet cell expression of vimentin indicates a degree of plasticity and dedifferentiation with potential loss of cellular identity in diabetes. This could contribute to α- and β-cell dysfunction in T2DM.

KW - Animals

KW - Case-Control Studies

KW - Cells, Cultured

KW - Diabetes Mellitus, Type 2

KW - Glucagon-Secreting Cells

KW - Humans

KW - Hyperinsulinism

KW - Insulin-Secreting Cells

KW - Macaca fascicularis

KW - Macaca mulatta

KW - Vimentin

KW - Journal Article

U2 - 10.1530/JOE-16-0588

DO - 10.1530/JOE-16-0588

M3 - Article

C2 - 28348116

SN - 0022-0795

VL - 233

SP - 217

EP - 227

JO - The Journal of endocrinology

JF - The Journal of endocrinology

IS - 3

ER -

Increased vimentin in human α- and β-cells in type 2 diabetes

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Keywords

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