Hypoglycemic effect of Astragalus polysaccharide and its effect on PTP1B.
OBJECTIVE
To examine the effects of Astragalus polysaccharide (APS), a component of an aqueous extract of Astragalus membranaceus roots, on protein tyrosine phosphatase 1B (PTP1B), a negative regulator of insulin-receptor (IR) signal transduction, and its potential role in the amelioration of insulin resistance.


METHODS
Ten-week-old fat-fed streptozotocin (STZ)-treated rats, an animal model of type II diabetes mellitus (TIIDM), were treated with APS (400 mg/kg p.o.) for 5 weeks. Insulin sensitivity was identified by the insulin-tolerance test. Further analyses on the possible changes in insulin signaling occurring in skeletal muscle and liver were performed by immunoprecipitation or Western blotting. PTP1B activity was measured by an assay kit.


RESULTS
The diabetic rats responded to APS with a significant decrease in body weight, plasma glucose, and improved insulin sensitivity. The activity and expression of PTP1B were elevated in the skeletal muscle and liver of TIIDM rats. Thus the insulin signaling in target tissues was diminished. APS reduced both PTP1B protein level and activity in the muscle, but not in the liver of TIIDM rats. Insulin-induced tyrosine phosphorylation of the IR beta-subunit and insulin receptor substrate-1 (IRS-1) were increased in the muscle, but not in the liver of APS-treated TIIDM rats. There was no change in the activity or expression of PTP1B in APS-treated normal rats, and blood insulin levels did not change in TIIDM rats after treatment with APS.


CONCLUSIONS
APS enables insulin-sensitizing and hypoglycemic activity at least in part by decreasing the elevated expression and activity of PTP1B in the skeletal muscles of TIIDM rats.
Wu
Yong
Y
Department of Pathophysiology, Medical College of Wuhan University, Wuhan 430060, China.
Ou-Yang
Jing-ping
JP
Wu
Ke
K
Wang
Ya
Y
Zhou
Yun-feng
YF
Wen
Chong-yuan
CY
D000818:Animals; D027885:Astragalus propinquus / Q000737:chemistry; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000201:enzymology* / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins; D008099:Liver / Q000201:enzymology; D008297:Male; D018482:Muscle, Skeletal / Q000201:enzymology; D010750:Phosphoproteins / Q000378:metabolism; D010946:Plants, Medicinal / Q000737:chemistry; D011134:Polysaccharides / Q000302:isolation & purification / Q000494:pharmacology*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011972:Receptor, Insulin / Q000378:metabolism
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D010750:Phosphoproteins; D011134:Polysaccharides; D011972:Receptor, Insulin; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases; C516610:Ptpn1 protein, rat