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TSPA as a novel ATF6α translocation inducer efficiently ameliorates insulin sensitivity restoration and glucose homeostasis in db/db mice.
- Source :
-
Biochemical & Biophysical Research Communications . May2018, Vol. 499 Issue 4, p948-953. 6p. - Publication Year :
- 2018
-
Abstract
- Activating transcription factor 6α (ATF6α) as a transducer in unfolded protein response (UPR), plays an important role in liver glucose metabolism and insulin resistance. Thus, targeting ATF6α activation has been proposed to be a potential strategy for anti-T2DM drug discovery. Here, we determined that small molecule 2-[5-[1-(4-chlorophenoxy)ethyl]-4-phenyl-4 H -1,2,4-triazol-3-yl]sulfanyl- N -(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1 H -pyrazol-4-yl)acetamide (TSPA) functioned as an ATF6α translocation inducer effectively promoting ATF6α translocation into nucleus and ameliorating glucose homeostasis on db/db mice. TSPA promoted ATF6α translocation into nucleus without incresing C/EBP-homologous protein (CHOP) expression. TSPA restored the tunicamycin (TM)-stimulated insulin receptor (IR) desensitization through ATF6α activation, inhibited gluconeogenesis and efficiently improved glucose homeostasis on db / db mice. Furthermore, TSPA protected insulin pathway involving p38/X-box binding protein 1s (Xbp1s)/ER chaperones signaling 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). [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 0006291X
- Volume :
- 499
- Issue :
- 4
- Database :
- Academic Search Index
- Journal :
- Biochemical & Biophysical Research Communications
- Publication Type :
- Academic Journal
- Accession number :
- 129152261
- Full Text :
- https://doi.org/10.1016/j.bbrc.2018.04.025