title: Islet remodeling in female mice with spontaneous autoimmune and streptozotocin-induced diabetes.
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.
authors.affiliation: Departments of Pathology and Laboratory Medicine, Child & Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Annette
authors.initials: A
authors.lastname: Plesner
authors.affiliation: Departments of Pathology and Laboratory Medicine, Child & Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Joris T
authors.initials: JT
authors.lastname: Ten Holder
authors.affiliation: Departments of Pathology and Laboratory Medicine, Child & Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada; Department of Surgery, Child & Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: C Bruce
authors.initials: CB
authors.lastname: Verchere
mesh_terms: D000818:Animals; D001786:Blood Glucose; D049109:Cell Proliferation; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000276:immunology / Q000473:pathology*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000276:immunology / Q000473:pathology*; D005260:Female; D005934:Glucagon / Q000097:blood; D052216:Glucagon-Like Peptide 1 / Q000097:blood / Q000378:metabolism; D050416:Glucagon-Secreting Cells / Q000473:pathology; D007150:Immunohistochemistry; D007328:Insulin / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D050417:Insulin-Secreting Cells / Q000473:pathology; D007515:Islets of Langerhans / Q000473:pathology*; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D013004:Somatostatin / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D007328:Insulin; D013004:Somatostatin; D052216:Glucagon-Like Peptide 1; D005934:Glucagon
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