Search

Abstract: Objective: Islet microcirculation is mainly composed by IMECs. The aim of the study was to investigate the differences in gene expression profiles of IMECs upon glucose toxicity exposure and insulin treatment. Methods: IMECs were treated with 5.6 mmol L−1 glucose, 35 mmol L−1 glucose, and 35 mmol L−1 glucose plus 10−8 mol L−1 insulin, respectively. Gene expression profiles were determined by microarray and verified by qPCR. GO terms and KEGG analysis were performed to assess the potential roles of differentially expressed genes. The interaction and expression tendency of differentially expressed genes were analyzed by Path‐Net algorithm. Results: Compared with glucose toxicity‐exposed IMECs, 1574 mRNAs in control group and 2870 mRNAs in insulin‐treated IMECs were identified with differential expression, respectively. GO and KEGG pathway analysis revealed that these genes conferred roles in regulation of apoptosis, proliferation, migration, adhesion, and metabolic process etc. Additionally, MAPK signaling pathway and apoptosis were the dominant nodes in Path‐Net. IMECs survival and function pathways were significantly changed, and the expression tendency of genes from euglycemia and glucose toxicity exposure to insulin treatment was revealed and enriched in 7 patterns. Conclusions: Our study provides a microcirculatory framework for gene expression profiles of glucose toxicity‐exposed IMECs. [ABSTRACT FROM AUTHOR]

Matrix metalloproteinases (MMPs) have been involved in inflammatory and degradative processes in pathologic conditions. The purpose of this study was to investigate the protective effect of melatonin in human umbilical vein endothelial cell (HUVEC) monolayer permeability and the regulation of MMP9 induced by interleukin 1&bgr; (IL1&bgr; (IL1B)) in HUVECs. Protection studies were carried out with melatonin, a well-known antioxidant and antiinflammatory molecule. MMP9 expression was increased with IL1&bgr; induction in HUVECs. Melatonin showed a barrier-protective role by downregulation of MMP9 and upregulation of tissue inhibitor of metalloproteinase-1 expression in HUVECs. Meanwhile, melatonin also decreased sodium fluorescein permeability and counteracted the downregulation of vascular endothelial cadherin and occludin expression in HUVECs. During inflammatory stimulus, nuclear factor-kB (NF-kB) plays a significant role in regulating MMP genes expression, thus the function of NF-kB in HUVECs' barrier disruption was investigated. IL1&bgr; induced nuclear translocation of NF-kB in HUVECs and regulated MMP9 expression. However, NF-kB translocation into the nucleus was inhibited significantly by melatonin. Our results show that melatonin decreases the permeability of monolayer endothelial cell induced by IL1&bgr;. At the same time, melatonin decreased the expression and activity of MMP9 by a NF-kB-dependent pathway in HUVECs induced by IL1&bgr;. [ABSTRACT FROM AUTHOR]