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. 2023 Apr 13;22:86. doi: 10.1186/s12933-023-01816-5

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© The Author(s) 2023

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 6 — The SGLT2 inhibitor improves ER stress. SGLT2 inhibitor treatment inhibits the loss of GRP78 from transducers by activating Sirt1, thus inhibiting the development of ER stress. The downstream signalling pathways of PERK, ATF6 and IRE1α can induce the transcription of CHOP. CHOP upregulates the expression of the pseudokinase tribbles homologue 3 gene and weakens the inhibitory effect of AKT on the expression of caspase-9 and caspase-3. On the other hand, CHOP promotes the expression of Bax and Bak and inhibits the expression of Bcl-2, Bcl-XL and MCL-1. IRE1α also promotes apoptosis by sequentially activating ASK1 and JNK