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Sphingolipids in Type 1 Diabetes: Focus on Beta-Cells

Type 1 diabetes (T1DM) is a chronic autoimmune disease, with a strong genetic background, leading to a gradual loss of pancreatic beta-cells, which secrete insulin and control glucose homeostasis. Patients with T1DM require life-long substitution with insulin and are at high risk for development of...

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Autor principal: Gurgul-Convey, Ewa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465050/
https://www.ncbi.nlm.nih.gov/pubmed/32759843
http://dx.doi.org/10.3390/cells9081835
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author Gurgul-Convey, Ewa
author_facet Gurgul-Convey, Ewa
author_sort Gurgul-Convey, Ewa
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description Type 1 diabetes (T1DM) is a chronic autoimmune disease, with a strong genetic background, leading to a gradual loss of pancreatic beta-cells, which secrete insulin and control glucose homeostasis. Patients with T1DM require life-long substitution with insulin and are at high risk for development of severe secondary complications. The incidence of T1DM has been continuously growing in the last decades, indicating an important contribution of environmental factors. Accumulating data indicates that sphingolipids may be crucially involved in T1DM development. The serum lipidome of T1DM patients is characterized by significantly altered sphingolipid composition compared to nondiabetic, healthy probands. Recently, several polymorphisms in the genes encoding the enzymatic machinery for sphingolipid production have been identified in T1DM individuals. Evidence gained from studies in rodent islets and beta-cells exposed to cytokines indicates dysregulation of the sphingolipid biosynthetic pathway and impaired function of several sphingolipids. Moreover, a number of glycosphingolipids have been suggested to act as beta-cell autoantigens. Studies in animal models of autoimmune diabetes, such as the Non Obese Diabetic (NOD) mouse and the LEW.1AR1-iddm (IDDM) rat, indicate a crucial role of sphingolipids in immune cell trafficking, islet infiltration and diabetes development. In this review, the up-to-date status on the findings about sphingolipids in T1DM will be provided, the under-investigated research areas will be identified and perspectives for future studies will be given.
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spelling pubmed-74650502020-09-04 Sphingolipids in Type 1 Diabetes: Focus on Beta-Cells Gurgul-Convey, Ewa Cells Review Type 1 diabetes (T1DM) is a chronic autoimmune disease, with a strong genetic background, leading to a gradual loss of pancreatic beta-cells, which secrete insulin and control glucose homeostasis. Patients with T1DM require life-long substitution with insulin and are at high risk for development of severe secondary complications. The incidence of T1DM has been continuously growing in the last decades, indicating an important contribution of environmental factors. Accumulating data indicates that sphingolipids may be crucially involved in T1DM development. The serum lipidome of T1DM patients is characterized by significantly altered sphingolipid composition compared to nondiabetic, healthy probands. Recently, several polymorphisms in the genes encoding the enzymatic machinery for sphingolipid production have been identified in T1DM individuals. Evidence gained from studies in rodent islets and beta-cells exposed to cytokines indicates dysregulation of the sphingolipid biosynthetic pathway and impaired function of several sphingolipids. Moreover, a number of glycosphingolipids have been suggested to act as beta-cell autoantigens. Studies in animal models of autoimmune diabetes, such as the Non Obese Diabetic (NOD) mouse and the LEW.1AR1-iddm (IDDM) rat, indicate a crucial role of sphingolipids in immune cell trafficking, islet infiltration and diabetes development. In this review, the up-to-date status on the findings about sphingolipids in T1DM will be provided, the under-investigated research areas will be identified and perspectives for future studies will be given. MDPI 2020-08-04 /pmc/articles/PMC7465050/ /pubmed/32759843 http://dx.doi.org/10.3390/cells9081835 Text en © 2020 by the author. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Gurgul-Convey, Ewa
Sphingolipids in Type 1 Diabetes: Focus on Beta-Cells
title Sphingolipids in Type 1 Diabetes: Focus on Beta-Cells
title_full Sphingolipids in Type 1 Diabetes: Focus on Beta-Cells
title_fullStr Sphingolipids in Type 1 Diabetes: Focus on Beta-Cells
title_full_unstemmed Sphingolipids in Type 1 Diabetes: Focus on Beta-Cells
title_short Sphingolipids in Type 1 Diabetes: Focus on Beta-Cells
title_sort sphingolipids in type 1 diabetes: focus on beta-cells
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465050/
https://www.ncbi.nlm.nih.gov/pubmed/32759843
http://dx.doi.org/10.3390/cells9081835
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