Unraveling the Pathogenesis of Type 1 Diabetes with Proteomics: Present And Future Directions
Year: 2005
Type: review
Abstract: Type 1 diabetes (T1D) is the result of selective destruction of the insulin-producing -cells in the pancreatic islets of Langerhans.T1D is due to a complex interplay between the -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 in particular, are present in the islets during -cell destruction and are able to modulate -cell function and induce -cell death.In -cells exposed to IL-1, 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 -cell.Proteomics has been applied in studies of differentiating -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 -cell lines, islets, and transplanted islets both in vitro and in vivo have been described.The data indicate that the -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 -cell to dynamic instability and eventually to -cell destruction. Molecular & Cellular Proteomics 4:441-457, 2005.Diabetes mellitus (DM) 1 is a group of disorders of multiple etiologies characterized by chronic hyperglycemia with dis-turbances of carbohydrate, fat, and protein metabolism resulting from defects in insulin secretion, insulin action, or both (1).Indian physicians were able in the 5-6 th century to distinguish between two forms of diabetes, one affecting elderly obese people (type 2 diabetes (T2D)) and the other affecting thin people who did not survive long (type 1 diabetes (T1D)).In 1922, the first T1D patient was treated with insulin.Before that time, no regular treatment of diabetes existed, and in best cases patients survived 2 or 3 years, but usually only for a few months (2).Based upon etiology, diabetes can be divided into four main groups (1) as described below.T1D-Absolute insulin deficiency due to an autoimmuneassociated destruction specifically of the insulin-producing -cells in the islets of Langerhans (Fig. 1).T2D-Relative insulin deficiency due to decreased effect of insulin in the target tissues e.g.muscles and adipose tissue (insulin resistance) or due to a secretory defect of insulin with or without insulin resistance.Other Specific Types of Diabetes-For example, specific genetic defects of -cell function, genetic defects in insulin action, diseases of the exocrine pancreas, endocrinopathies, drug or chemically induced, infections, uncommon forms of immune-mediated diabetes, and other genetic syndromes sometimes associated with diabetes.Gestational Diabetes-Carbohydrate intolerance resulting in hyperglycemia of variable serverity with onset or first recognition during pregnancy (includes gestational impaired glucose tolerance and gestational diabetes).The metabolic state between normal glucose homeostasis and diabetes encompasses a state termed "impaired glucose regulation" (impaired glucose tolerance (IGT) and impaired fasting glycaemia (IFG)).Individuals with IGT or IFG may be normo-glycaemic in daily life with normal or near-normal glycated hemoglobin levels.IGT and IFG are not independent clinical entities, but are rather risk categories for future dia-From
Source: Molecular & Cellular Proteomics
Institution: University of Southern Denmark
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,430
OpenAlex ID: W2017136097