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Islet remodeling in female mice with spontaneous autoimmune and streptozotocin-induced diabetes.

Plesner A, Ten Holder JT, Verchere CB - PLoS ONE (2014)

Bottom Line: Islet alpha- and delta-cells are spared autoimmune destruction directed at beta-cells in type 1 diabetes resulting in an apparent increase of non-beta endocrine cells in the islet core.Serum levels of insulin, glucagon and GLP-1 were measured to compare hormone levels with respect to disease state.Alpha- or delta-cell mass in STZ-diabetic mice did not normalize by replacement of insulin via osmotic mini-pumps or islet transplantation.

View Article: PubMed Central - PubMed

Affiliation: Departments of Pathology and Laboratory Medicine, Child & Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.

ABSTRACT
Islet alpha- and delta-cells are spared autoimmune destruction directed at beta-cells in type 1 diabetes resulting in an apparent increase of non-beta endocrine cells in the islet core. We determined how islet remodeling in autoimmune diabetes compares to streptozotocin (STZ)-induced diabetes. Islet cell mass, proliferation, and immune cell infiltration in pancreas sections from diabetic NOD mice and mice with STZ-induced diabetes was assessed using quantitative image analysis. Serial sections were stained for various beta-cell markers and Ngn3, typically restricted to embryonic tissue, was only upregulated in diabetic NOD mouse islets. Serum levels of insulin, glucagon and GLP-1 were measured to compare hormone levels with respect to disease state. Total pancreatic alpha-cell mass did not change as autoimmune diabetes developed in NOD mice despite the proportion of islet area comprised of alpha- and delta-cells increased. By contrast, alpha- and delta-cell mass was increased in mice with STZ-induced diabetes. Serum levels of glucagon reflected these changes in alpha-cell mass: glucagon levels remained constant in NOD mice over time but increased significantly in STZ-induced diabetes. Increased serum GLP-1 levels were found in both models of diabetes, likely due to alpha-cell expression of prohormone convertase 1/3. Alpha- or delta-cell mass in STZ-diabetic mice did not normalize by replacement of insulin via osmotic mini-pumps or islet transplantation. Hence, the inflammatory milieu in NOD mouse islets may restrict alpha-cell expansion highlighting important differences between these two diabetes models and raising the possibility that increased alpha-cell mass might contribute to the hyperglycemia observed in the STZ model.

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Related in: MedlinePlus

Islet endocrine cell changes during progression of autoimmune diabetes as leukocyte infiltration increases and dissipates.Serial pancreas sections from 4(red) and somatostatin (green), or glucagon (red) and CD45-positive leukocytes (green). Scale bar = 10 µm.
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pone-0102843-g002: Islet endocrine cell changes during progression of autoimmune diabetes as leukocyte infiltration increases and dissipates.Serial pancreas sections from 4(red) and somatostatin (green), or glucagon (red) and CD45-positive leukocytes (green). Scale bar = 10 µm.

Mentions: In young (4 wk old) diabetes-prone NOD mice, glucagon-, insulin- and somatostatin-positive cells comprised most of the islet area (84.9±1.8%; Fig. 1a). In older (12 wk old) mice with insulitis and in diabetic (18–24 wk old) NOD mice, the proportion of islet area comprised of these major islet endocrine cell types diminished to 68.0±11.2% and 61.7±4.3%, respectively as the number of infiltrating immune cells in the islets increased markedly, as demonstrated by CD45-staining (Fig. 1 and 2).


Islet remodeling in female mice with spontaneous autoimmune and streptozotocin-induced diabetes.

Plesner A, Ten Holder JT, Verchere CB - PLoS ONE (2014)

Islet endocrine cell changes during progression of autoimmune diabetes as leukocyte infiltration increases and dissipates.Serial pancreas sections from 4(red) and somatostatin (green), or glucagon (red) and CD45-positive leukocytes (green). Scale bar = 10 µm.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4125302&req=5

pone-0102843-g002: Islet endocrine cell changes during progression of autoimmune diabetes as leukocyte infiltration increases and dissipates.Serial pancreas sections from 4(red) and somatostatin (green), or glucagon (red) and CD45-positive leukocytes (green). Scale bar = 10 µm.
Mentions: In young (4 wk old) diabetes-prone NOD mice, glucagon-, insulin- and somatostatin-positive cells comprised most of the islet area (84.9±1.8%; Fig. 1a). In older (12 wk old) mice with insulitis and in diabetic (18–24 wk old) NOD mice, the proportion of islet area comprised of these major islet endocrine cell types diminished to 68.0±11.2% and 61.7±4.3%, respectively as the number of infiltrating immune cells in the islets increased markedly, as demonstrated by CD45-staining (Fig. 1 and 2).

Bottom Line: Islet alpha- and delta-cells are spared autoimmune destruction directed at beta-cells in type 1 diabetes resulting in an apparent increase of non-beta endocrine cells in the islet core.Serum levels of insulin, glucagon and GLP-1 were measured to compare hormone levels with respect to disease state.Alpha- or delta-cell mass in STZ-diabetic mice did not normalize by replacement of insulin via osmotic mini-pumps or islet transplantation.

View Article: PubMed Central - PubMed

Affiliation: Departments of Pathology and Laboratory Medicine, Child & Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.

ABSTRACT
Islet alpha- and delta-cells are spared autoimmune destruction directed at beta-cells in type 1 diabetes resulting in an apparent increase of non-beta endocrine cells in the islet core. We determined how islet remodeling in autoimmune diabetes compares to streptozotocin (STZ)-induced diabetes. Islet cell mass, proliferation, and immune cell infiltration in pancreas sections from diabetic NOD mice and mice with STZ-induced diabetes was assessed using quantitative image analysis. Serial sections were stained for various beta-cell markers and Ngn3, typically restricted to embryonic tissue, was only upregulated in diabetic NOD mouse islets. Serum levels of insulin, glucagon and GLP-1 were measured to compare hormone levels with respect to disease state. Total pancreatic alpha-cell mass did not change as autoimmune diabetes developed in NOD mice despite the proportion of islet area comprised of alpha- and delta-cells increased. By contrast, alpha- and delta-cell mass was increased in mice with STZ-induced diabetes. Serum levels of glucagon reflected these changes in alpha-cell mass: glucagon levels remained constant in NOD mice over time but increased significantly in STZ-induced diabetes. Increased serum GLP-1 levels were found in both models of diabetes, likely due to alpha-cell expression of prohormone convertase 1/3. Alpha- or delta-cell mass in STZ-diabetic mice did not normalize by replacement of insulin via osmotic mini-pumps or islet transplantation. Hence, the inflammatory milieu in NOD mouse islets may restrict alpha-cell expansion highlighting important differences between these two diabetes models and raising the possibility that increased alpha-cell mass might contribute to the hyperglycemia observed in the STZ model.

Show MeSH
Related in: MedlinePlus