Effect of magnesium sulfate administration to improve insulin resistance in type 2 diabetes animal model: using the hyperinsulinemic-euglycemic clamp technique.

Abstract

This study attempted to elucidate the possible mechanism of magnesium sulfate (MgSO4 ) administration on reducing insulin resistance in type 2 diabetic rats. Fifty Wistar rats were divided into five groups: NDC was fed the normal diet, CD received high-fat diet with 35 mg/kg of streptozotocin, CD-Mg animals received MgSO4 via drinking water, CD-Ins1, and CD-Ins2 animals treated with low or high dose of insulin. Body weight and blood glucose levels were measured weekly. Intraperitoneal glucose tolerance test (IPGTT), insulin tolerance test, and metabolic cage assessment were performed monthly. After 12 weeks, the hyperinsulinemic-euglycemic clamp was performed for all animals and blood sample was taken to measure glycated hemoglobin (HbA1c), plasma insulin, glucagon, calcium, and magnesium levels. Liver and gastrocnemius muscle were isolated to measure glucagon receptor (GR), Glucose 6 phosphatase (G6Pase), Phosphoenolpyruvate carboxykinase (Pepck) and Glucose transporter 4 (Glut4) genes expression and GLUT4 protein translocation into the cell membrane. Consuming of high-fat diet generated insulin-resistant rats. Magnesium or insulin therapy altered insulin resistance, blood glucose, IPGTT, gluconeogenesis pathway, GR, body weight, the percentage of body fat, and HbA1C in diabetic rats. Administrations of MgSO4 or insulin in Type 2 diabetes mellitus animals increase GLUT4 gene and protein expression. Mg could improve glucose tolerance via stimulation of Glut4 gene expression and translocation and also suppression of the gluconeogenesis pathway and GR gene expression. Mg also increased glucose infusion rate and displayed beneficial effects in the treatment of glucose metabolism and improved insulin resistance.

• Authors: Shahla Sohrabipour, Mohammad Reza Sharifi, Mohammadreza Sharifi, Ardeshir Talebi, Nepton Soltani
• Journal: Fundamental & clinical pharmacology (Fundam Clin Pharmacol) Vol. 32 Issue 6 Pg. 603-616 (Dec 2018) ISSN: 1472-8206 [Electronic] England
• PMID: 29869808 (Publication Type: Journal Article)
• Copyright: © 2018 Société Française de Pharmacologie et de Thérapeutique.

Chemical References

• Blood Glucose
• Glucose Transporter Type 4
• Hypoglycemic Agents
• Insulin
• Streptozocin
• Magnesium Sulfate
• Glucose

Topics

• Animals
• Blood Glucose (drug effects)
• Diabetes Mellitus, Experimental (drug therapy, metabolism)
• Diabetes Mellitus, Type 2 (drug therapy, metabolism)
• Diet, High-Fat
• Disease Models, Animal
• Gluconeogenesis (drug effects)
• Glucose (metabolism)
• Glucose Clamp Technique (methods)
• Glucose Tolerance Test (methods)
• Glucose Transporter Type 4 (metabolism)
• Hypoglycemic Agents (pharmacology)
• Insulin (metabolism)
• Insulin Resistance (physiology)
• Liver (drug effects, metabolism)
• Magnesium Sulfate (pharmacology)
• Male
• Muscle, Skeletal (drug effects, metabolism)
• Rats
• Rats, Wistar
• Streptozocin (pharmacology)