Comparison of Acute Gene Expression Profiles of Islet Cells Obtained via Laser Capture Microdissection between Alloxan- and Streptozotocin-treated Rats

Abstract

To identify the molecular profiles of islets from alloxan (ALX)- and streptozotocin (STZ)-treated rats, a microarray-based global gene expression analysis was performed on frozen islets isolated via laser capture microdissection. At 6 weeks old, rats were injected with ALX (40 mg/kg) or STZ (50 or 100 mg/kg) and then euthanized 24 hr later. Histopathological analysis showed β-cell necrosis, macrophage infiltration, and islet atrophy. The extent of these changes was more notable in the STZ groups than in the ALX group. Transcriptome analysis demonstrated a significant up- or downregulation of cell cycle arrest-related genes in the p53 signaling pathway. Cyclin D2 and cyclin-dependent kinase inhibitor 1A, mediators of G1 arrest, were remarkably altered in STZ-treated rats. In contrast, cyclin-B1 and cyclin-dependent kinase 1, mediators of G2 arrest, were remarkably changed in ALX-treated rats. Genes involved in the intrinsic mitochondria-mediated apoptotic pathway were upregulated in the ALX and STZ groups. Moreover, heat-shock 70 kDA protein 1A ( Hspa1a), Hsp90ab1, and Hsph1 were upregulated in ALX-treated rats, suggesting that ALX treatment injures β cells via endoplasmic reticulum stress. These results contribute to a better understanding of gene expression in the pathogenesis of islet toxicity.

Chemokines as Drivers of the Autoimmune Destruction in Type 1 Diabetes: Opportunity for Therapeutic Intervention in Consideration of an Optimal Treatment Schedule

“…Thereby, RNA can be isolated from the entire islet microenvironment, selected regions containing exclusively intact b-cells or infiltrating cells, or even from single b-cells (39). Indeed, laser-capture micro-dissection has been performed in pancreas section of healthy controls, patients with T1D, as well as of several mouse and rat models (37,40,41). Although some of these studies have identified proteins involved in immune cell migration to be upregulated in T1D (42), the focus of these studies was often on other topics and therefore a clear conclusion on the role of chemokines is still missing.…”