• The Therapeutic Effects of Magnesium in Insulin Secretion and Insulin Resistance
  • Azadehalsadat Hosseini Dastgerdi,1,* Mahtab Ghanbari Rad,2 Nepton Soltani,3
    1. Department of medicine, Na.C., Islamic Azad University, Najafabad, Iran
    2. Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
    3. Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran


  • Introduction: Insulin resistance is a chronic pathological condition that is related to reduce the rates of glucose uptake, especially in the liver, muscle, and adipose tissue as target tissues, and it occurs when insulin receptors (INRs) lose their sensitivity to insulin. Insulin controls energy homeostasis and glucose metabolism by stimulating glucose uptake from skeletal muscle and, to a lesser degree, liver and adipose tissue. In adipose tissue and skeletal muscle, glucose transporter 4 (GLUT4) is the main isoform of GLUTs that participate in insulin stimulated glucose uptake based on translocation of GLUT4 from an intracellular pool to the plasma membrane. Hence, IR is associated with defects at the level of GLUT4 content in skeletal muscles and adipose tissue that leads to enhancing the concentration of insulin in the circulatory system as a compensatory mechanism. Type 2 diabetes (T2D) as a chronic disease is characterized by hyperglycemia due to impaired insulin secretion, insulin function, or both. Chronic hyperglycemia is the main risk factor for heart disease, stroke, kidney disease, blindness, and amputation. Unfortunately, the World Health Organization reported that the prevalence of diabetes is rapidly increasing all around the world and there has been an epidemic increase in mortality from T2D. It is expected that the number of people suffering from diabetes will reach 25%–28% by 2050. To overcome this situation, some approaches have been made to find some medications that may increase insulin sensitivity and improve T2D complications. Quite recently, considerable attention has been paid to magnesium (Mg2+) as a potential option for balancing glucose uptake. Mg2+ is the fourth most important element in the human body and the second most abundant intracellular cation. Mg2+ involves in more than 300 enzymatic reactions and numerous physiological processes by acting as a cofactor for many enzymes such as energy metabolism, glucose transport across cell membrane, hepatic gluconeogenesis, pancreatic functions, insulin secretion, and action in pancreatic cells and target tissues through interaction with receptors of this hormone. With this aim in mind, we reviewed Mg2+ performance in improving IR.
  • Methods: To identify relevant studies, the search was performed in Google Scholar, PubMed, Scopus, and Web of Science. The search was carried out from 1983 until 2021. The keywords used in the search were insulin resistance, skeletal muscle, liver, pancreases, magnesium, Mg2+, and inflammation without language or date restrictions. The title and abstract of all the articles were studied and those describing mechanisms of IR and therapeutic effects of Mg2+ in reducing IR were finally selected.
  • Results: Mg2+ has numerous duties in the human body such as regulation of insulin secretion in pancreatic beta cells and phosphorylation of the insulin receptors in target cells and also gets involved in other downstream signal kinases as intracellular cation. On this basis, intracellular Mg2+ balancing is vital for adequate carbohydrate metabolism. Based on the research reviewed in this article, it can be concluded that normal Mg2+ serum level is essential for optimal functioning of many enzymes in insulin secretion and also glucose and energy metabolism. Mg2+ is associated with improvement in beta cell function, decreasing IR, accelerating glucose tolerance, and ultimately, clinical. improvement of T2D. Oral Mg2+ supplementation and appropriate dietary patterns improve insulin sensitivity and metabolic control in individuals with T2D, suggesting that Mg2+ is an important factor in the etiology and management of this widespread socially significant disease. In addition, it is worth highlighting that Mg2+ acts as the insulin sensitizer by regulating Tyrosine Kinase activity of the receptor of this hormone and autophosphorylation of this receptor b subunit, with ensuing phosphorylation of its substrates mediators, and favors the manifestation of IR. Mg2+ improves glucose consumption and glucose tolerance, at least in part, via stimulation of GLUT4 gene expression and translocation and also suppression of the gluconeogenesis pathway and glucagon receptor gene expression by targeting the liver and muscle.
  • Conclusion: According to the results of our study and the previous ones, we can conclude that not only Mg2+ supplementation can be helpful in diabetes control, but also the effective dosage and duration of supplementation, and the patients who need the supplementation should be considered. Therefore, Mg2+ is also recommended as an inexpensive, easy to use, natural adjuvant therapy for patients with T2D.
  • Keywords: Diabetes, glucose, insulin resistance, magnesium