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. 2013 Jun 17;2(3):243–255. doi: 10.1016/j.molmet.2013.06.003

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© 2013 The Authors

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-No Derivative Works License, which permits non-commercial use, distribution, and reproduction in any medium, provided the original author and source are credited.

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Role of Nor-1 in incretin-induced insulin expression and secretion and hypothetical localization of the TCF7L2 and NR4A3 SNP effects. The well-known TCF7L2 SNP rs7903146 leads to impaired incretin response, inhibited PKA pathway, and reduced insulin secretion (dashed lines). Based on our molecular data, we propose a gain-of-function mechanism in NR4A3 SNP rs12686676 carriers independent of incretin action. Increased Nor-1 expression enhances insulin secretion in these subjects probably by induction of genes encoding for exocytosis proteins and maybe by increasing intracellular insulin content thereby bypassing the defect caused by the TCF7L2 SNP (solid lines).