biostudies-literatureBorg DJNational Health and Medical Research CouncilAustralian Research Council426https://www.ebi.ac.uk/biostudies/studies/S-EPMC8305727biostudies-literatureUnknown11(7)Mechanisms by which advanced glycation end products (AGEs) contribute to type 1 diabetes (T1D) pathogenesis are poorly understood. Since life-long pharmacotherapy with alagebrium chloride (ALT) slows progression to experimental T1D, we hypothesized that acute ALT therapy delivered prediabetes, may be effective. However, in female, non-obese diabetic (NOD<i>ShiLt</i>) mice, ALT administered prediabetes (day 50-100) did not protect against experimental T1D. ALT did not decrease circulating AGEs or their precursors. Despite this, pancreatic β-cell function was improved, and insulitis and pancreatic CD45.1⁺ cell infiltration was reduced. Lymphoid tissues were unaffected. ALT pre-treatment, prior to transfer of primed GC98 CD8⁺ T cell receptor transgenic T cells, reduced bMetabolitesShort Duration Alagebrium Chloride Therapy Prediabetes Does Not Inhibit Progression to Autoimmune Diabetes in an Experimental Model.PMC8305727FT1101003721023664, 1165490, 1084283, 1043315, 1137739, 1004503, 1102935Briskey DPurcell AWForbes JMGiam KLMcCarthy DAAyala RScheijen JLSchalkwijk CGFaridi PDudek NLWard MSSteptoe RFotheringham AKHarcourt BEBorg DJReeves PLeung SfalseShort Duration Alagebrium Chloride Therapy Prediabetes Does Not Inhibit Progression to Autoimmune Diabetes in an Experimental Model.Mechanisms by which advanced glycation end products (AGEs) contribute to type 1 diabetes (T1D) pathogenesis are poorly understood. Since life-long pharmacotherapy with alagebrium chloride (ALT) slows progression to experimental T1D, we hypothesized that acute ALT therapy delivered prediabetes, may be effective. However, in female, non-obese diabetic (NOD<i>ShiLt</i>) mice, ALT administered prediabetes (day 50-100) did not protect against experimental T1D. ALT did not decrease circulating AGEs or their precursors. Despite this, pancreatic β-cell function was improved, and insulitis and pancreatic CD45.1⁺ cell infiltration was reduced. Lymphoid tissues were unaffected. ALT pre-treatment, prior to transfer of primed GC98 CD8⁺ T cell receptor transgenic T cells, reduced b2021-01-01T00:00:00Z2021 Jun2026-04-08T07:30:10.234Z2026-04-07T23:42:31.162ZS-EPMC83057273420347110.3390/metabo11070426