| Popis: |
Obesity-induced inflammation has been proposed to be a factor in onset and progression of type 2 diabetes, marked by dysfunction of pancreatic beta-cells. Pro-inflammatory cytokines, specifically the obesity-induced IL-6 and IL-1 beta, have been indicated. Zinc, calcium, and iron are essential metals for proper function of beta-cells, yet it is not well understood how obesity-induced inflammation influences metals in beta-cells. This study was undertaken to investigate the metallome of pancreatic beta-cells and compare those results to the metallome of cells exposed to obesity-induced pro-inflammatory cytokines. To study the metallome of beta-cells, synchrotron X-ray florescent (SXRF) microscopy was performed. SXRF is a technique that allows quantification and visualization of multiple metals in a single cell simultaneously. The collected data showed significant zinc depletion, a redistribution and reduction of calcium, and an accumulation of iron in unique iron structures after exposure to cytokines. Investigation of gene expression in beta-cells after exposure to cytokines revealed upregulation of zinc transporters consistent with increase in intracellular zinc and granular zinc, in addition to a significant upregulation of iron-regulating genes, which are consistent with iron accumulation. An investigation of gene expression of ER stress and unfolded protein response (UPR) markers suggests that after exposure to cytokines, beta-cells induce UPR. In summary, this work, for the first time, reported details of the beta-cell metallome and showed cytokine-induced changes are potentially adaptive. |
