Islet Inflammation and Fibrosis in a Spontaneous Model of Type 2 Diabetes, the GK Rat
- Françoise Homo-Delarche1,
- Sophie Calderari1,
- Jean-Claude Irminger2,
- Marie-Noëlle Gangnerau1,
- Josiane Coulaud1,
- Katharina Rickenbach2,
- Manuel Dolz1,
- Philippe Halban2,
- Bernard Portha1 and
- Patricia Serradas1
- 1Unité Mixte de Recherche 7059, National Center for Scientific Research, Diderot University, Paris, France
- 2Department of Genetic Medecine and Development, University Medical Center, Geneva, Switzerland
- Address correspondence and reprint requests to Francoise Homo-Delarche, CNRS UMR 7059, Université Paris 7/D. Diderot, 2, place Jussieu, 75005 Paris, France. E-mail: francoise.homo-delarche{at}paris7.jussieu.fr
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.
Footnotes
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F.H.-D., S.C., and J.-C.I. contributed equally to this work.
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DOI: 10.2337/db05-1526
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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- Accepted February 27, 2006.
- Received November 23, 2005.
- DIABETES
