Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Evidence that the etiology of the syndrome containing type 2 diabetes mellitus results from abnormal magnesium metabolism. 1841 43

Magnesium (Mg) is the second most abundant intracellular cation where it plays an important role in enzyme function and trans-membrane ion transport. Mg deficiency has been associated with a number of clinical disorders including osteoporosis. Osteoporosis is common problem accounting for 2 million fractures per year in the United States at a cost of over $17 billion dollars. The average dietary Mg intake in women is 68% of the RDA, indicating that a large proportion of our population has substantial dietary Mg deficits. The objective of this paper is to review the evidence for Mg deficiency-induced osteoporosis and potential reasons why this occurs, including a cumulative review of work in our laboratories and well as a review of other published studies linking Mg deficiency to osteoporosis. Epidemiological studies have linked dietary Mg deficiency to osteoporosis. As diets deficient in Mg are also deficient in other nutrients that may affect bone, studies have been carried out with select dietary Mg depletion in animal models. Severe Mg deficiency in the rat (Mg at <0.0002% of total diet; normal = 0.05%) causes impaired bone growth, osteopenia and skeletal fragility. This degree of Mg deficiency probably does not commonly exist in the human population. We have therefore induced dietary Mg deprivation in the rat at 10%, 25% and 50% of recommended nutrient requirement. We observed bone loss, decrease in osteoblasts, and an increase in osteoclasts by histomorphometry. Such reduced Mg intake levels are present in our population. We also investigated potential mechanisms for bone loss in Mg deficiency. Studies in humans and and our rat model demonstrated low serum parathyroid hormone (PTH) and 1,25(OH)(2)-vitamin D levels, which may contribute to reduced bone formation. It is known that cytokines can increase osteoclastic bone resorption. Mg deficiency in the rat and/or mouse results in increased skeletal substance P, which in turn stimulates production of cytokines. With the use of immunohistocytochemistry, we found that Mg deficiency resulted in an increase in substance P, TNFalpha and IL1beta. Additional studies assessing the relative presence of receptor activator of nuclear factor kB ligand (RANKL) and its decoy receptor, osteoprotegerin (OPG), found a decrease in OPG and an increase in RANKL favoring an increase in bone resorption. These data support the notion at dietary Mg intake at levels not uncommon in humans may perturb bone and mineral metabolism and be a risk factor for osteoporosis.
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PMID:Skeletal and hormonal effects of magnesium deficiency. 1982 98


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