Back to Search
Start Over
Astragalus polysaccharides decreased the expression of PTP1B through relieving ER stress induced activation of ATF6 in a rat model of type 2 diabetes
- Source :
- Molecular and cellular endocrinology. 307(1-2)
- Publication Year :
- 2008
-
Abstract
- Protein tyrosine phosphatase 1B (PTP1B) was considered as a potential therapeutic target of type 2 diabetes (T2DM) because of its negative regulation of insulin signaling. It located on the cytosolic surface of endoplasmic reticulum (ER) and played an essential role in the ER stress signaling. Activating transcription factor 6 (ATF6) was an ER stress regulated transmembrane transcription factor that activated the transcription of ER molecular chaperones. We hypothesized that the expression of PTP1B may be regulated by ATF6 when ER stress happened. Our previous studies showed that Astragalus polysaccharide (APS) increased the insulin sensitivity through decreasing the overexpression of PTP1B in T2DM animal models. In this study, we intended to investigate the possible mechanisms involved in this effect. A rat model of T2DM was established using high fat diet associated with intraperitoneal injection of 25 mg/kg streptozocin; 25 mmol/l D-glucose and 5x10(-7) mol/l insulin were used as in vitro investigations to mimic T2DM-like environment. 4-(2-Aminoethyl) benzenesulfonyl fluoride hydrochloride (AEBSF) and pCI-Flag-ATF6(N)(2-366) plasmid were treated separately on human hepatocyte line HL-7702 to observe the effect of ATF6 on the expression of PTP1B. The results suggested that APS not only restored the glucose homeostasis but also reduced the ER stress in this rat model of T2DM; ATF6 was involved in mediating the expression of PTP1B when ER stress happened; APS decreased the expression of PTP1B at least partly through inhibiting the activation of ATF6.
- Subjects :
- medicine.medical_specialty
medicine.medical_treatment
Activating transcription factor
Endoplasmic Reticulum
Transfection
Biochemistry
Cell Line
Diabetes Mellitus, Experimental
Rats, Sprague-Dawley
chemistry.chemical_compound
Endocrinology
Polysaccharides
Stress, Physiological
Internal medicine
AEBSF
medicine
Glucose homeostasis
Animals
Homeostasis
Humans
Insulin
Sulfones
Molecular Biology
Protein Tyrosine Phosphatase, Non-Receptor Type 1
biology
ATF6
Endoplasmic reticulum
Astragalus Plant
Activating Transcription Factor 6
Rats
Insulin receptor
Disease Models, Animal
Glucose
chemistry
Liver
biology.protein
Unfolded protein response
Plasmids
Subjects
Details
- ISSN :
- 18728057
- Volume :
- 307
- Issue :
- 1-2
- Database :
- OpenAIRE
- Journal :
- Molecular and cellular endocrinology
- Accession number :
- edsair.doi.dedup.....30f97123015d460d660e8c8c9ccb47d3