Astragalus polysaccharides decreased the expression of PTP1B through relieving ER stress induced activation of ATF6 in a rat model of type 2 diabetes.
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.
Wang
Nian
N
Department of Pathophysiology, Medical College of Wuhan University, Hubei Provincial Key Laboratory of Allergy and Immune-Related Diseases, Wuhan, People's Republic of China.
Zhang
Deling
D
Mao
XianQing
X
Zou
Feng
F
Jin
Huan
H
Ouyang
JingPing
J
D051702:Activating Transcription Factor 6 / Q000378:metabolism*; D000818:Animals; D027883:Astragalus Plant / Q000737:chemistry*; D002460:Cell Line; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology* / Q000473:pathology; D004195:Disease Models, Animal; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000473:pathology*; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D010957:Plasmids; D011134:Polysaccharides / Q000494:pharmacology*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological / Q000187:drug effects*; D013450:Sulfones / Q000494:pharmacology; D014162:Transfection
D051702:Activating Transcription Factor 6; D007328:Insulin; D011134:Polysaccharides; D013450:Sulfones; C002010:4-(2-aminoethyl)benzenesulfonylfluoride; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; C516610:Ptpn1 protein, rat; D005947:Glucose