Abstract
Type 1 diabetes (T1D) is the result of selective destruction of the insulin-producing beta-cells in the pancreatic islets of Langerhans. T1D is due to a complex interplay between the beta-cell, the immune system, and the environment in genetically susceptible individuals. The initiating mechanism(s) behind the development of T1D are largely unknown, and no genes or proteins are specific for most T1D cases. Different pro-apoptotic cytokines, IL-1 beta in particular, are present in the islets during beta-cell destruction and are able to modulate beta-cell function and induce beta-cell death. In beta-cells exposed to IL-1 beta, a race between destructive and protective events are initiated and in susceptible individuals the deleterious events prevail. Proteins are involved in most cellular processes, and it is thus expected that their cumulative expression profile reflects the specific activity of cells. Proteomics may be useful in describing the protein expression profile and thus the diabetic phenotype. Relatively few studies using proteomics technologies to investigate the T1D pathogenesis have been published to date despite the defined target organ, the beta-cell. Proteomics has been applied in studies of differentiating beta-cells, cytokine exposed islets, dietary manipulated islets, and in transplanted islets. Although that the studies have revealed a complex and detailed picture of the protein expression profiles many functional implications remain to be answered. In conclusion, a rather detailed picture of protein expression in beta-cell lines, islets, and transplanted islets both in vitro and in vivo have been described. The data indicate that the beta-cell is an active participant in its own destruction during diabetes development. No single protein alone seems to be responsible for the development of diabetes. Rather the cumulative pattern of changes seems to be what favors a transition from dynamic stability in the unperturbed beta-cell to dynamic instability and eventually to beta-cell destruction.
Highlights
Diabetes mellitus (DM)1 is a group of disorders of multiple etiologies characterized by chronic hyperglycemia with disturbances of carbohydrate, fat, and protein metabolism resulting from defects in insulin secretion, insulin action, or both [1]
This study aims to describe the relevance of the proteins identified in vitro after IL-1 exposure for the development of diabetes in vivo in syngeneically transplanted prediabetic BB-DP rats and in diabetes-resistant BioBreeding (BB-DR) and Wistar Furth (WF) rat islets
Today it is beyond any doubt that Type 1 diabetes (T1D) is a multifactorial polygenic disease of largely unknown etiology
Summary
Our published studies have yielded a complex and detailed picture of protein expression changes associated with maturation into the -cell phenotype, cytokine-mediated -cell destruction, and islet destruction in vitro and in vivo during diabetes development. The purpose is to identify and describe the changes in protein expression specific for -cells or of proteins induced by IL-1 exposure of Wistar Furth (WF) and BB-DP islets in vitro and in vivo during development of diabetes, respectively (Fig. 2). In this study we have identified and followed IL-1-induced changes in protein expression in vitro in syngeneically transplanted islets and have related these changes to the development of diabetes in the BB-DP rat. We have produced a rather detailed picture of protein expression during development of diabetes in the BB-DP rat and produced evidence to support that IL-1-induced in vitro protein expression changes in islets occur during autoimmune -cell destruction. Proteins that are changed in expression despite their origin are believed to play a role in changing the stability of the -cell and are as such of potential interest
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