Diabetes Research Today is a free monthly online journal that collates and summarizes the latest research about Diabetes, including details on insulin, type i, type ii, diet, treatment, prevention.

Immune-mediated beta-cell destruction in vitro and in vivo-A pivotal role for galectin-3.

Karlsen AE, Størling ZM, Sparre T, Larsen MR, Mahmood A, Størling J, Roepstorff P, Wrzesinski K, Larsen PM, Fey S, Nielsen K, Heding P, Ricordi C, Johannesen J, Kristiansen OP, Christensen UB, Kockum I, Luthman H, Nerup J, Pociot F

Steno Diabetes Center, Gentofte, Denmark. aek@novonordisk.com

Pro-apoptotic cytokines are toxic to the pancreatic beta-cells and have been associated with the pathogenesis of Type 1 diabetes (T1D). Proteome analysis of IL-1beta exposed isolated rat islets identified galectin-3 (gal-3) as the most up-regulated protein. Here analysis of human and rat islets and insulinoma cells confirmed IL-1beta regulated gal-3 expression of several gal-3 isoforms and a complex in vivo expression profile during diabetes development in rats. Over-expression of gal-3 protected beta-cells against IL-1beta toxicity, with a complete blockage of JNK phosphorylation, essential for IL-1-mediated apoptosis. Mutation scanning of regulatory and coding regions of the gal-3 gene (LGALS3) identified six polymorphisms. A haplotype comprising three cSNPs showed significantly increased transmission to unaffected offspring in 257 T1D families and replicated in an independent set of 170 T1D families. In summary, combined proteome-transcriptome-genome and functional analyses identify gal-3 as a candidate gene/protein in T1D susceptibility that may prove valuable in future intervention/prevention strategies.

Published 24 April 2006 in Biochem Biophys Res Commun, 344(1): 406-15.
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