Our observations raise the question of whether metformin treatment could reduce oxidative stress and act as an ER stress modulator in T2D patients by promoting an adaptive unfolded protein response (s-xbp1 and p-eIF2α) in their leukocytes; this was in contrast with nonmetformin-treated patients whose response could be driven by the ATF6-dependent pro-apoptotic pathway.
Our current study has determined that ATF6α was a promising therapeutic target and also highlighted the potential of TSPA in the treatment of type 2 diabetes mellitus (T2DM).
Studies in Pima Indian, Caucasians and African Americans identified several SNPs in DUSP12 and ATF6, located in chromosome 1q21-q23, were associated with type 2 diabetes.
Although the associations with type 2 diabetes and plasma insulin levels are marginal and their functional consequences are yet unknown, all three amino acid substitutions are located in a functionally important part of ATF6.