Total Astragalus saponins can reverse type 2 diabetes mellitus-related intestinal dysbiosis and hepatic insulin resistance in vivo

Front Endocrinol (Lausanne). 2023 Nov 20:14:1190827. doi: 10.3389/fendo.2023.1190827. eCollection 2023.

Abstract

Objective: Intestinal flora homeostasis in rats with type 2 diabetes mellitus (T2DM) was evaluated to explore the effects of total Astragalus saponins (TAS) on hepatic insulin resistance (IR).

Methods: Six-week-old male Sprague-Dawley rats were fed high-fat and high-sugar diet for 4 weeks and intraperitoneally injected with streptozotocin to induce T2DM, and they were then randomly divided into control, model, metformin, and TAS groups. Stool, serum, colon, and liver samples were collected after 8 weeks of drug administration for relevant analyses.

Results: TAS reduced fasting blood glucose, 2-hour postprandial blood glucose, area under the curve of oral glucose tolerance test, glycated serum protein, homeostasis model assessment of insulin resistance, total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels in T2DM rats but increased insulin, C-peptide, and high-density lipoprotein cholesterol levels. Moreover, TAS improved the morphology and structure of liver and colon tissues and improved the composition of the intestinal microbiome and bacterial community structure at different taxonomic levels. In addition, TAS increased the protein expression of hepatic IRS-1, PI3K, PDK1, and p-AKT and decreased the protein expression of p-GSK-3β. Meanwhile, TAS increased the mRNA expression of liver PDK1, PI3K, and GS and decreased the mRNA expression of GSK-3β.

Conclusion: TAS can ameliorate T2DM-related abnormal glucose and blood lipid metabolism, intestinal dysbiosis, and IR.

Keywords: gut-liver axis; insulin resistance; intestinal microbiota; total Astragalus saponins; type 2 diabetes mellitus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / metabolism
  • Cholesterol / metabolism
  • Diabetes Mellitus, Experimental* / complications
  • Diabetes Mellitus, Experimental* / drug therapy
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / drug therapy
  • Dysbiosis / drug therapy
  • Glycogen Synthase Kinase 3 beta / metabolism
  • Glycogen Synthase Kinase 3 beta / pharmacology
  • Insulin Resistance*
  • Liver / metabolism
  • Male
  • Phosphatidylinositol 3-Kinases / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Saponins* / metabolism
  • Saponins* / pharmacology

Substances

  • Blood Glucose
  • Glycogen Synthase Kinase 3 beta
  • Saponins
  • Phosphatidylinositol 3-Kinases
  • RNA, Messenger
  • Cholesterol

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by a grant for regular science and technology assistance projects for developing countries from the Ministry of Science and Technology (KY201904005) and a grant from the Tangshan Pharmacological Foundation Innovation Team of Traditional Chinese Medicine for Prevention and Treatment of Diabetes (19130205C) and Supported by the project of High level group for research and innovation of School of Public Health, North China University of Science and Technology(KYTD202311) and Hebei Provincial Administration of Traditional Chinese Medicine Research Plan Project (2020222).