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Islet Inflammation and Fibrosis in a Spontaneous Model of Type 2 Diabetes, the GK Rat

2006; American Diabetes Association; Volume: 55; Issue: 6 Linguagem: Inglês

10.2337/db05-1526

1939-327X

Françoise Homo‐Delarche, Sophie Caldérari, Jean-Claude Irminger, Marie-Noëlle Gangnerau, Josiane Coulaud, Katharina Rickenbach, Manuel Dolz, Philippe A. Halban, Bernard Portha, Patricia Serradas,

Diet, Metabolism, and Disease

The molecular pathways leading to islet fibrosis in diabetes are unknown. Therefore, we studied gene expression in islets of 4-month-old Goto-Kakizaki (GK) and Wistar control rats. Of 71 genes found to be overexpressed in GK islets, 24% belong to extracellular matrix (ECM)/cell adhesion and 34% to inflammatory/immune response families. Based on gene data, we selected several antibodies to study fibrosis development during progression of hyperglycemia by immunohistochemistry. One-month-old GK and Wistar islets appeared to be similar. Two-month-old GK islets were strongly heterogenous in terms of ECM accumulation compared with Wistar islets. GK islet vascularization, labeled by von Willebrand factor, was altered after 1 month of mild hyperglycemia. Numerous macrophages (major histocompatibility complex class II+ and CD68+) and granulocytes were found in/around GK islets. These data demonstrate that marked inflammatory reaction accompanies GK islet fibrosis and suggest that islet alterations in this nonobese model of type 2 diabetes develop in a way reminiscent of microangiopathy.