предыдущий|следующий

Phlorizin Ameliorates Glucose and Lipid Metabolism Disorders in T2DM Rats by Modulating IRS-1/PI3K/Akt Signaling Pathway

  • role： First author第一作者
  • Affiliation：

    Jiangxi University of Chinese Medicine， Nanchang 330004，China

  • Email：nuerailiaili@163.com
  • Introduction：努尔·艾力，在读硕士，从事中药资源与药效学研究，E-mail：nuerailiaili@163.com
Nuer Aili1,  
  • Affiliation：

    Nanchang Medical College， Nanchang 330052，China

CAO Qingyu2,  
  • Affiliation：

    Jiangxi University of Chinese Medicine， Nanchang 330004，China

LIU Huan1,  
  • Affiliation：

    Jiangxi University of Chinese Medicine， Nanchang 330004，China

HE Junwei1,  
  • role： Corresponding author通信作者
  • Affiliation：

    Jiangxi University of Chinese Medicine， Nanchang 330004，China

  • Email：zhongweihong@jxutcm.edu.cn
  • Introduction：钟卫红，讲师，从事中药和民族药资源与品质评价研究，E-mail：zhongweihong@jxutcm.edu.cn
ZHONG Weihong1*,  
  • role： Corresponding author通信作者
  • Affiliation：

    Jiangxi University of Chinese Medicine， Nanchang 330004，China

  • Email：674179402@qq.com
  • Introduction：曹岚，硕士，副教授，从事中药资源与民族药研究，E-mail：674179402@qq.com； *
CAO Lan1*

реферат

ObjectiveTo observe the pharmacodynamic efficacy of phlorizin in improving hepatic glycolipid metabolism disorders in type 2 diabetic mellitus （T2DM） rats and to explore its mechanism of action based on the insulin receptor substrate-1 （IRS-1）/phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway.MethodsA high-fat diet and streptozotocin （STZ） were used to establish T2DM rat models. The rats were randomly assigned into six groups： the blank control group， model group， metformin group （300 mg·kg-1）， and phlorizin high-dose （100 mg·kg-1） and low-dose groups （25 mg·kg-1）. The rats were given intragastric administration for 6 weeks. The changes in body weight and fasting blood glucose （FBG） were observed， and the oral glucose tolerance test （OGTT） was carried out. The levels of total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， glycated serum protein （GSP）， aspartate aminotransferase （AST）， and alanine aminotransferase （ALT） in serum were detected by an automatic biochemical analyzer. The levels of fasting insulin （FINS）， interleukin （IL）-1β， IL-6， and tumour necrosis factor （TNF）-α were detected by enzyme-linked immunosorbent assay （ELISA）. The levels of superoxide dismutase （SOD） and malondialdehyde （MDA） were detected by the biochemical assays. The pancreas index， liver index， and insulin resistance index were calculated. Hematoxylin-eosin （HE） staining was used to evaluate the pathological changes in liver and pancreatic tissues. The immunofluorescence method was used to detect the changes in insulin and glucagon in pancreatic tissue. Western blot was used to detect the expression of related proteins in the IRS-1/PI3K/Akt pathway of liver tissue and its downstream glycogen synthase kinase-3β （GSK-3β） and forkhead box transcription factor O1 （FoxO1） proteins.ResultsCompared with the blank control group， the body weight of rats in the model group continued to decrease， while the FBG level increased significantly. The area under the OGTT blood glucose curve （AUC）， GSP， TC， TG， LDL-C， IL-1β， IL-6， TNF-α， MDA， pancreatic index and liver index increased significantly， while the levels of HDL-C， SOD， and FINS decreased significantly （P0.05， P0.01）. Histological results showed that the pancreatic islets of rats in the model group exhibited atrophy and severe structural abnormalities. The insulin-positive β-cells decreased significantly （P0.01）， while the glucagon-positive α-cells increased significantly （P0.01）. Inflammatory cell infiltration and partial necrosis were observed in the liver tissues of the model group rats. The expressions of p-IRS-1/IRS-1， p-GSK-3β/GSK-3β， and p-FoxO1/FoxO1 proteins in the liver of the model group increased significantly （P0.01）， while the expressions of p-PI3K/PI3K and p-Akt/Akt proteins decreased significantly （P0.01）. Compared with the model group， the diabetic symptoms of rats in all administration groups were improved. The changes in body weight and FBG were close to those of the blank control group. The levels of OGTT-AUC， GSP， TC， TG， LDL-C， MDA， IL-1β， IL-6， TNF-α and the pancreatic index， liver index were obviously reduced （P0.05， P0.01）， while the levels of HDL-C， SOD， and FINS obviously increased （P0.05， P0.01）. The pathological changes of the pancreas and liver in rats in all treatment groups were effectively improved. The insulin-positive β-cells in the pancreas increased significantly （P0.01）， while the glucagon-positive α-cells decreased significantly （P0.01）. The protein expressions of p-IRS-1/IRS-1， p-GSK-3β/GSK-3β， and p-FoxO1/FoxO1 in the liver were significantly reduced （P0.01）， while the protein expressions of p-PI3K/PI3K and p-Akt/Akt significantly increased （P0.01）.ConclusionPhlorizin reversed the weight loss and abnormal increase of FBG in T2DM rats， improved blood lipid profiles， oxidative stress， and inflammatory levels， alleviated insulin resistance， and had certain protective effects on the liver and pancreas. The hypoglycemic mechanism may involve regulating the IRS-1/PI3K/Akt signaling pathway to inhibit the activities of GSK-3β and FoxO1， thereby promoting liver glycogen synthesis and suppressing hepatic gluconeogenesis， ultimately improving glycolipid metabolism disorders.

ключеви́че слова́

phlorizin;insulin receptor substrate-1（IRS-1）/phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）;type 2 diabetes mellitus （T2DM）;insulin resistance;glucose and lipid metabolism

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