Glucose uptake is mediated by a family of glucose transport proteins, which are known to be expressed in specific insulin-sensitive tissues. Magnesium (Mg) is essential for autophosrylation of insulin receptor (INSR) and translocation of glucose transporter 4 (GLUT4) to the plasma membrane to facilitate glucose homeostasis. The specific effect of magnesium on INSR and GLUT4 expression in a diabetic state is however lacking. We conducted this study to investigate whether magnesium supplementation alters INSR and GLUT4 expression in the insulin-responsive skeletal muscle, and whether this contributes to improved glucose homeostasis in type 2 diabetic (T2D) rats.
Thirty-two (32) male Sprague-Dawley rats were randomly divided into four groups consisting of control, diabetic untreated (DU), diabetic treated with 1 mg of Mg/kg diet (Mg1-D) and diabetic rats treated with 2 mg of Mg/kg diet (Mg2-D). T2D was induced with a single intraperitoneal (i.P) injection of nicotinamide (120 mg/kg BW) and streptozotocin (55 mg/kg BW). Animals with blood glucose level above 200 mg/dl were considered to be diabetic. Glucose and insulin tolerance tests, lipid and oxidative parameters as well as expression of INSR and GLUT4 were determined in all experimental rats. The obtained data was analyzed by GraphPad Prism (v. 5) using One-way analysis of variance (ANOVA).
Diabetes resulted in impaired glucose tolerance and insulin resistance. Mg supplementation in diabetic rats however improved glucose tolerance with increased insulin sensitivity. Fasting glucose, cholesterol, triglyceride, high density lipoprotein (HDL) levels as well as HOMA-IR were significantly increased in diabetic rats (DU vs CTR); these were however normalized to near control values by Mg supplementation. In addition, Mg treatment attenuated the diabetes-induced decrease in the expression of INSR and GLUT4 receptors in the gastrocnemius muscle of the diabetic rats.
This study demonstrates that Mg decreases the metabolic disturbance associated with T2D, improving glucose/insulin metabolism through an increased expression of INSR and GLUT4 receptors.