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

Homo-Delarche, Francoise; Calderari, Sophie; Irminger, Jean-Claude; Gangnerau, M. N.; Coulaud, Josiane; Rickenbach, Katharina; Dolz, Manuel; Halban, Philippe A.; Portha, Bernard; Serradas, Patricia

doi:10.2337/db05-1526

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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 Irminger, Jean-Claude Gangnerau, M. N. Coulaud, Josiane Rickenbach, Katharina Dolz, Manuel Halban, Philippe A. Portha, Bernard Serradas, Patricia show all authors [1 - 10]
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		Animals — Cell Adhesion/genetics — Diabetes Mellitus, Type 2/genetics/metabolism/ pathology — Disease Models, Animal — Extracellular Matrix/metabolism — Fibrosis — Gene Expression Profiling — Hyperglycemia/genetics/metabolism/pathology — Immunohistochemistry — Inflammation/genetics/immunology/metabolism — Islets of Langerhans/immunology/metabolism/ pathology — Macrophages/metabolism/pathology — Male — Oligonucleotide Array Sequence Analysis — Rats — Rats, Wistar — Reverse Transcriptase Polymerase Chain Reaction
Identifiers		DOI: 10.2337/db05-1526 PMID: 16731824
Full text		Article - Limited access to UNIGE Other version: http://diabetes.diabetesjournals.org/content/55/6/1625.full.pdf
Structures		Faculté de médecine / Section de médecine clinique / Département de médecine
Citation (ISO format)		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. doi: 10.2337/db05-1526 https://archive-ouverte.unige.ch/unige:8813