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Title

Islet inflammation and fibrosis in a spontaneous model of type 2 diabetes, the GK rat

Authors
Homo-Delarche, Francoise
Calderari, Sophie
Gangnerau, M. N.
Coulaud, Josiane
Dolz, Manuel
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Published in Diabetes. 2006, vol. 55, no. 6, p. 1625-1633
Abstract 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.
Keywords AnimalsCell Adhesion/geneticsDiabetes Mellitus, Type 2/genetics/metabolism/ pathologyDisease Models, AnimalExtracellular Matrix/metabolismFibrosisGene Expression ProfilingHyperglycemia/genetics/metabolism/pathologyImmunohistochemistryInflammation/genetics/immunology/metabolismIslets of Langerhans/immunology/metabolism/ pathologyMacrophages/metabolism/pathologyMaleOligonucleotide Array Sequence AnalysisRatsRats, WistarReverse Transcriptase Polymerase Chain Reaction
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PMID: 16731824
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HOMO-DELARCHE, Francoise et al. Islet inflammation and fibrosis in a spontaneous model of type 2 diabetes, the GK rat. In: Diabetes, 2006, vol. 55, n° 6, p. 1625-1633. https://archive-ouverte.unige.ch/unige:8813

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Deposited on : 2010-07-12

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