Effects of selenium and exendin-4 on glucagon-like peptide-1 receptor, IRS-1, and Raf-1 in the liver of diabetic rats

Biochem Genet. 2012 Dec;50(11-12):922-35. doi: 10.1007/s10528-012-9532-2. Epub 2012 Sep 16.

Abstract

Selenium and exendin-4 exert antidiabetic effects by unknown mechanisms. Herein, we investigated their effects on the expression of glucagon-like peptide-1 receptor (GLP-1R), insulin receptor substrate-1 (IRS-1), and Raf-1 in the livers of rats with streptozotocin-induced diabetes. Diabetic rats were injected intraperitoneally with exendin-4 (0.03 μg/kg body weight) twice daily or treated with 5 ppm selenium as sodium selenite in drinking water for 4 weeks. Both selenium and exendin-4 reduced the hyperglycemia in diabetic rats. Induction of diabetes mellitus resulted in decreased level of GLP-1R and increased levels of IRS-1 and Raf-1 in the liver. Treatment of diabetic rats with selenium or exendin-4 resulted in increased level of GLP-1R and decreased levels of IRS-1 and Raf-1 in the liver, compared with the levels in diabetic rats. Therefore, the antidiabetic actions of selenium and exendin-4 involve their effects on GLP-1R, IRS-1, and Raf-1 levels in the liver.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose
  • Blotting, Western
  • Diabetes Mellitus, Experimental / drug therapy
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / pathology
  • Exenatide
  • Glucagon-Like Peptide-1 Receptor
  • Hypoglycemic Agents / pharmacology
  • Insulin / metabolism
  • Insulin / pharmacology
  • Insulin Receptor Substrate Proteins / genetics
  • Insulin Receptor Substrate Proteins / metabolism*
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / pathology
  • MAP Kinase Kinase Kinases / genetics
  • MAP Kinase Kinase Kinases / metabolism*
  • Male
  • Peptides / administration & dosage
  • Peptides / pharmacology*
  • Proto-Oncogene Proteins c-raf
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Glucagon / genetics
  • Receptors, Glucagon / metabolism*
  • Selenium / metabolism
  • Selenium / pharmacology
  • Sodium Selenite / administration & dosage
  • Sodium Selenite / pharmacology*
  • Streptozocin / administration & dosage
  • Streptozocin / adverse effects
  • Time Factors
  • Venoms / administration & dosage
  • Venoms / pharmacology*

Substances

  • Blood Glucose
  • Glp1r protein, rat
  • Glucagon-Like Peptide-1 Receptor
  • Hypoglycemic Agents
  • Insulin
  • Insulin Receptor Substrate Proteins
  • Irs1 protein, rat
  • Peptides
  • RNA, Messenger
  • Receptors, Glucagon
  • Venoms
  • Streptozocin
  • Exenatide
  • Proto-Oncogene Proteins c-raf
  • Raf1 protein, rat
  • MAP Kinase Kinase Kinases
  • Selenium
  • Sodium Selenite