Astragalus polysaccharides affect insulin resistance by regulating the hepatic SIRT1-PGC-1α/PPARα-FGF21 signaling pathway in male Sprague Dawley rats undergoing catch-up growth.
The present study investigated the effects of Astragalus polysaccharides (APS) on insulin resistance by modulation of hepatic sirtuin 1 (SIRT1)‑peroxisome proliferator‑activated receptor (PPAR)‑γ coactivator (PGC)‑1α/PPARα‑fibroblast growth factor (FGF)21, and glucose and lipid metabolism. Thirty male Sprague Dawley rats were divided into three groups: A normal control group, a catch‑up growth group and an APS‑treated (APS-G) group. The latter two groups underwent food restriction for 4 weeks, prior to being provided with a high fat diet, which was available ad libitum. The APS‑G group was orally treated with APS for 8 weeks, whereas the other groups were administered saline. Body weight was measured and an oral glucose tolerance test (OGTT) was conducted after 8 weeks. The plasma glucose and insulin levels obtained from the OGTT were assayed, and hepatic morphology was observed by light and transmission electron microscopy. In addition, the mRNA expression levels of PGC‑1α/PPARα, and the protein expression levels of SIRT1, FGF21 and nuclear factor‑κB were quantified in the liver and serum. APS treatment suppressed abnormal glycolipid metabolism and insulin resistance following 8 weeks of catch‑up growth by improving hepatic SIRT1‑PPARα‑FGF21 intracellular signaling and reducing chronic inflammation, and by partially attenuating hepatic steatosis. The suppressive effects of APS on liver acetylation and glycolipid metabolism‑associated molecules contributed to the observed suppression of insulin resistance. However, the mechanism underlying the effects of APS on insulin resistance requires further research in order to be elucidated. Rapid and long‑term treatment with APS may provide a novel, safe and effective therapeutic strategy for type 2 diabetes.
Department of Endocrinology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai 201399, P.R. China.
Chengying
C
Gu
Department of Traditional Chinese Medicine, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai 201399, P.R. China.
Yipeng
Y
Zeng
Department of Endocrinology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, P.R. China.
Zhaosheng
Z
Tang
Department of Endocrinology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai 201399, P.R. China.
Chaoxun
C
Wang
Department of Endocrinology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai 201399, P.R. China.
Yanju
Y
He
Department of Traditional Chinese Medicine, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai 201399, P.R. China.
Xinge
X
Feng
Department of Endocrinology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai 201399, P.R. China.
Ligang
L
Zhou
D000818:Animals; D027883:Astragalus Plant / Q000737:chemistry*; D001786:Blood Glucose / Q000187:drug effects; D031204:Caloric Restriction; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D059305:Diet, High-Fat / Q000009:adverse effects; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics / Q000473:pathology; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D005951:Glucose Tolerance Test; D006801:Humans; D000960:Hypolipidemic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D007333:Insulin Resistance; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011134:Polysaccharides / Q000302:isolation & purification / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D001786:Blood Glucose; D000960:Hypolipidemic Agents; D047493:PPAR alpha; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011134:Polysaccharides; C501429:Ppargc1a protein, rat; D014157:Transcription Factors; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors; C488368:Sirt1 protein, rat; D056564:Sirtuin 1