Novel players in the rescue of ß-cells from inflammation-mediated destruction in type 2 diabetes mellitus
|Other Titles:||Neue Ansätze zur Inhibierung der entzündungsvermittelten ß-Zellzerstörung bei Typ-2-Diabetes mellitus||Authors:||Gitanjali, Dharmadhikari||Supervisor:||Mädler, Kathrin||1. Expert:||Mädler, Kathrin||2. Expert:||Bonifacio, Ezio||Abstract:||
Chronic inflammation is consequential to the etiology of both T1D and T2D. Cytokine and chemokine production by infiltrating macrophages and by ß-cells themselves in a diabetic milieu contributes to their destruction in inflamed islets and thus to progression of diabetes. In order to find potential targets for inhibition of this deleterious response of islets, the investigation of underlying mechanisms for triggering inflammation is essential. The expression of a novel family of adhesion molecules called Sialic acid-binding immunoglobulin-like lectins (Siglecs) in pancreatic islets was observed in cell type specific manner. Siglec-7, expressed on the ß-cells, was down-regulated in diabetes. Over-expression of Siglec-7 in cultured isolated islets prevented ß-cell dysfunction and apoptosis under chronic diabetic stimuli and also in diabetic islets. The protective effect of Siglec-7 was mediated by the inhibition of the NF-κB pathway and the subsequent decrease in cytokine secretion. Also, activated immune cells showed loss of Siglec-7 expression. Ultimately, restoration of Siglec-7 in stressed islets caused a reduction in the number of recruited migrating monocytes. Siglec-7 expression on ß-cells contributes to the inhibition of pro-inflammatory activation of these cells in diabetes. Restoration of Siglec-7 expression or signaling may be a potential therapeutic strategy to preserve ß-cell function and mass in the manifestation of diabetes. This strategy would not only rescue the ß-cells, but also inhibit systemic inflammation observed in T2D.
|Keywords:||diabetes ß-cell siglec inflammation||Issue Date:||15-Oct-2013||Type:||Dissertation||URN:||urn:nbn:de:gbv:46-00103606-14||Institution:||Universität Bremen||Faculty:||FB2 Biologie/Chemie|
|Appears in Collections:||Dissertationen|
checked on Jan 19, 2021
checked on Jan 19, 2021
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