Increased vimentin in human α- and β-cells in type 2 diabetes
- Maaike M Roefs1,*,
- Françoise Carlotti1,*,
- Katherine Jones2,
- Hannah Wills2,
- Alexander Hamilton2,
- Michael Verschoor1,
- Joanna M Williams Durkin1,
- Laura Garcia-Perez1,
- Melissa F Brereton3,
- Laura McCulloch2,
- Marten A Engelse1,
- Paul R V Johnson2,4,
- Barbara C Hansen5,
- Kevin Docherty6,
- Eelco J P de Koning1,7 and
- Anne Clark2⇑
- 1Department of Internal Medicine, Leiden University Medical Center (LUMC), Leiden, the Netherlands
- 2Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), Oxford, UK
- 3Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK
- 4Nuffield Department of Surgical Sciences, John Radcliffe Hospital, Oxford, UK
- 5Departments of Internal Medicine and Pediatrics, Morsani College of Medicine, University of South Florida, Tampa, Florida, USA
- 6Medical Sciences, University of Aberdeen, Aberdeen, UK
- 7Hubrecht Institute, Utrecht, the Netherlands
- Correspondence should be addressed to A Clark; Email: anne.clark{at}drl.ox.ac.uk
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Figure 1
The mesenchymal protein vimentin is expressed in a subset of human α- and β-cells in T2DM. (A, B) Islet from non-diabetic (ND) subject labelled for vimentin (white) and (A) insulin (red) and (B) glucagon (green). Insets show cells double labelled for the islet peptide and vimentin. (C, D) Islet from subject with type 2 diabetes (T2DM) labelled for vimentin (white) and (C) insulin (red) and (D) glucagon (green). Insets show cells double labelled for the islet peptide and vimentin. Scale bars = 50 µm. (E, F) Quantitative data of the frequency of vimentin+insulin+ cells (E) and vimentin+glucagon+ cells/subject (F) in pancreatic sections from subjects without (ND) and with T2DM. Graphs represent individual values (as scatter plots) and median values ± interquartile range (as box plots, *P < 0.05). Vimentin+glucagon+ cells were more frequent than vimentin+glucagon+ cells in both ND and T2DM subjects (note the differences in axis values).
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Figure 2
Ultrastructural identification of vimentin in human islets. Immunogold labelling for vimentin in islet from ND subject (A, B) and a subject with T2DM (C, D). Labelling was not detected in either α-cells (A) or β-cells (B) in islets from ND subjects although labelling was present in perivascular fibroblasts in all islets. (C) Vimentin was present as patches of cytoplasmic intermediate filaments (arrows) in α-cells in islets isolated from patients with T2DM. (D) In β-cells of islets from a diabetic subject, vimentin labelling was present in primary lysosomes (lys) (arrows) and infrequently in cytoplasmic intermediate filaments. g, glucagon granules; i, insulin granules; lb, lipofuscin body; m, mitochondrion; n, nucleus. Scale bars 500 nm.
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Figure 3
Vimentin+insulin+ cells rarely express the key β-cell transcription factor Nkx6.1. (A) Islet labelled for vimentin (white), insulin (red) and Nkx6.1 (green). Insets show a cell double labelled for insulin and vimentin (arrow), as well as an insulin+Nkx6.1+ (white arrow head) and insulin+Nkx6.1− cell (yellow arrow head). Scale bar 20 µm. (B) Quantification data on samples from the Leiden cohort. The majority of insulin+ cells express Nkx6.1 (B, left panel), whereas most vimentin+insulin+ cells were Nkx6.1 negative (B, right panel). (C) Islet labelled for vimentin (white), insulin (red) and Pdx1 (green). Most vimentin+insulin+ cells were Pdx1 negative. Scale bar 50 µm. Insets show a cell double labelled for insulin and vimentin. (D) Islet from a subject with T2DM labelled for vimentin (green), insulin (blue) and glucagon (red). Vimentin-positive cells (arrows) were positive for glucagon but not insulin. Scale bar 20 µm.
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Figure 4
Vimentin expression in β-cells is higher in diabetic non-human primates. (A, B) Islets from non-diabetic non-human primates (ND) labelled for vimentin (white) and (A) insulin (red) and (B) glucagon (green). Insets show cells double labelled for the islet peptide and vimentin. (C, D) Islets from diabetic animals (DM) labelled for vimentin (white) and (C) insulin (red) and (D) glucagon (green). The islets from diabetic animals usually contained islet amyloid, as seen in (C) as an area devoid of cells/nuclei. Insets show cells double labelled for the islet peptide and vimentin. Scale bars = 50 µm. (E, F) Quantitative data of the frequency of vimentin+insulin+ cells (E) and vimentin+glucagon+ cells/subject (F) in pancreatic sections from non-diabetic (ND), hyperinsulinaemic (HI) and diabetic (DM) animals. Graphs represent individual values (as scatter plots) and median values ± interquartile range (as box plots, *P < 0.05).
- © 2017 Society for Endocrinology
