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. Author manuscript; available in PMC: 2013 Jul 11.
Published in final edited form as: Nat Rev Endocrinol. 2011 May 24;7(9):526–539. doi: 10.1038/nrendo.2011.74

Figure 4.

Figure 4

AGEs impair insulin secretion in pancreatic islet β cells. This process can occur via several pathways: by iNOS induction, and through the generation of mitochondrial ROS, AGEs suppress cytochrome C oxidase levels and ATP generation, reducing membrane depolarization and insulin release; by suppressing insulin gene promoter activity; by suppressing SIRT1, which regulates UCP2, impairing β-cell depolarization and secretory function; by promoting immune cell (T cell, macrophage) recruitment, activation and β-cell cytotoxicity, apoptosis or cell death. AGER1 normally suppresses the effects of AGEs and ROS and may enhance SIRT1 expression and function in β cells, positively regulating insulin secretion. Under chronic high-level AGE conditions, AGER1 is downregulated, which may contribute to β-cell dysfunction or destruction. Abbreviations: AGE, advanced glycation endproduct; AGER1, AGE receptor 1; CytC, cytochrome c; iNOS, inducible nitric oxide synthase; SIRT1, NAD-dependent deacetylase sirtuin-1; UCP2, mitochondrial uncoupling protein 2.