Evidence that the etiology of the syndrome containing type 2 diabetes mellitus results from abnormal magnesium metabolism

Abstract

Evidence is reviewed supporting the presence of an inherited structural defect in the plasma membranes of somatic cells of humans who have type 2 diabetes mellitus and sodium-sensitive essential hypertension. This magnesium-binding defect (MgBD) consists of a decreased content of tightly bound Mg2+ ion in the cell membrane and limits the amount of Mg2+ that enters the cell, some of which combines with ATP4-, produced by the cell, to form MgATP2-, the currency of metabolic energy. Consequently, in both prediabetes and overt diabetes, the intracellular concentration of the interdependent Mg2+ and MgATP2- ions is significantly less than normal. These 2 ions are required as cofactors and (or) substrates for some 300 enzyme systems in human metabolism, many of which are involved with insulin. Thus the decreased activities of particular ones of these enzyme systems due to the decreased intracellular [Mg2+] and its dependent [MgATP2-] are responsible for (i) insulin resistance and (ii) decreased insulin secretion and (or) production, the 2 pathophysiological processes required for the occurrence of type 2 diabetes mellitus. These 2 processes can account for all of the morbid symptoms associated with this disease. Thus, the decreased intracellular concentration of the interdependent Mg2+ and MgATP2- ions constitutes the etiology of genetic predisposition to type 2 diabetes mellitus and can be corrected by 2 identified peptide Mg2+-binding promoters that are derived from the carboxyl terminal of the tachykinin substance P and occur in normal blood plasma. Decreased intracellular [Mg2+] and [MgATP2-] can also result from a dietary deficiency of magnesium or from an abnormal accumulation of saturated fatty acids in cell membranes, which inhibits the entrance of Mg2+ into the cell; thus it is also the etiology not only of diabetes caused by magnesium deficiency, but also of the "lipotoxic" type 2 diabetes mellitus. Although these pathologies cannot be corrected by the Mg2+-binding promoters, they can be corrected, respectively, by dietary magnesium supplementation or by exercise plus dietary caloric and lipid restriction. Theoretically, the disease syndrome containing type 2 diabetes mellitus may involve approximately 30% of the population.

Altered metabolism of copper, zinc, and magnesium is associated with increased levels of glycated hemoglobin in patients with diabetes mellitus

“…The relationship between hypomagnesemia and insulin resistance, impaired glucose tolerance, as well as decreased insulin secretion has been suggested by recent studies [18,21,22]. Reduced plasma levels of Mg have been documented in both type 1 and type 2 DM (T1DM and T2DM, respectively), especially in poorly controlled DM [23]. The cause of hypomagnesemia was attributed to osmotic renal losses from glycosuria, decreased intestinal absorption, and redistribution of Mg from the plasma into blood cells caused by insulin effect [24,25].…”

Effect of melatonin on element distribution in the liver tissue of diabetic rats subjected to forced exercise

“…It is known that magnesium levels drop in diabetic patients (22). Elevated magnesium levels we found with melatonin supplementation in the group 6 (melatonin-supplemented diabetic swimming) in our study maight be evaluated as a striking result, in consideration of the effects of this element in the glucose metabolism (20,21). Physical activity was shown to result in an increase in manganese activity in rats (22) However, it is also known that excessive accumulation of manganese causes lipid peroxidation through a toxic effect (23).…”

“…The highest liver magnesium was found in the group 6 (melatonin-supplemented diabetic swimming) and the highest manganese levels were established in the groups 6 (melatonin-supplemented diabetic swimming), 7 (diabetic swimming) and 8 (diabetes). Magnesium is associated with enzyme activities that involve insulin (20). Therefore, magnesium is involved in mechanisms regulating the blood glucose (21).…”

Comparative Proximate Composition and Hypoglycemic Properties of Three Medicinal Plants (Verononia amygdalina, Azadirachta indica and Moringa oleifera).

“…[55][56] In addition, low magnesium levels have been associated with increased type II diabetes. [57][58][59] Results of comparative proximate composition of the three plants showed appreciable AC (Figure 1), which suggest that V. amygdalina, A. indica and M. oleifera contain relatively rich quantity of inorganic trace elements posited to possessing glycemic control property. In similar manner, CFBC of V. amygdalina, A. indica and M. oleifera advance the view that the plants products are agents of glycemic control.…”