Oxymatrine ameliorates insulin resistance in rats with type 2 diabetes by regulating the expression of KSRP, PETN, and AKT in the liver

J Cell Biochem. 2019 Sep;120(9):16185-16194. doi: 10.1002/jcb.28898. Epub 2019 May 14.

Abstract

Insulin resistance plays a key role in the development and progression of type 2 diabetes mellitus (T2DM). Recent studies found that insulin resistance was associated with the dysfunction of KH-type splicing regulatory protein (KSRP) expression and AKT pathway, and that oxymatrine possesses an antidiabetic effect. The aim of the present study was to investigate whether the protection of oxymatrine against T2DM was associated with the modulation of the KSRP expression and AKT pathway. Sprague-Dawley rats were fed a high-fat diet and injected with streptozotocin intraperitoneally to induce T2DM, which led to an increase in blood glucose levels and insulin resistance, and a decrease in insulin sensitivity and glycogen synthesis concomitant with KSRP downregulation, PTEN upregulation, and AKT phosphorylation deficiency. The administration of oxymatrine decreased blood glucose levels and insulin resistance, increased insulin sensitivity, and improved glycogen synthesis in the liver of T2DM rats, through a reversal in the expression of KSRP, PTEN, and AKT. On the basis of these observations, we concluded that oxymatrine can protect T2DM rats from insulin resistance through the regulation of the KSRP, PETN, and AKT expression in the liver.

Keywords: AKT; KH-type splicing regulatory protein (KSRP); PETN; insulin resistance; oxymatrine; type 2 diabetes mellitus (T2DM).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / administration & dosage*
  • Alkaloids / pharmacology
  • Animals
  • Blood Glucose / drug effects
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / metabolism
  • Diet, High-Fat / adverse effects*
  • Gene Expression Regulation / drug effects
  • Injections, Intraperitoneal
  • Insulin Resistance
  • Male
  • PTEN Phosphohydrolase / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Quinolizines / administration & dosage*
  • Quinolizines / pharmacology
  • RNA-Binding Proteins / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Streptozocin
  • Trans-Activators / metabolism*

Substances

  • Alkaloids
  • Blood Glucose
  • KHSRP protein, rat
  • Quinolizines
  • RNA-Binding Proteins
  • Trans-Activators
  • Streptozocin
  • oxymatrine
  • Proto-Oncogene Proteins c-akt
  • PTEN Phosphohydrolase
  • Pten protein, rat