Impaired tyrosine-kinase activity of muscle insulin receptors from hypomagnesaemic rats

Abstract

The effect of magnesium deficiency on glucose disposal, glucose-stimulated insulin secretion and insulin action on skeletal muscle was investigated in rats which were fed a low magnesium-containing diet for 4 days. Control rats were fed a standard diet. Compared to the control rats, the rats fed with low magnesium diet presented: 1) lower serum magnesium levels (0.45 +/- 0.02 vs 0.78 +/- 0.01 mmol/l, p < 0.001), 2) higher basal serum glucose (6.8 +/- 0.02 vs 5.5 +/- 0.2 mmol/l, p < 0.05) and similar basal serum insulin, 3) 40% reduction (p < 0.001) in the glucose disappearance rate after its i.v. administration, and 4) 45% reduction (p < 0.05) in the glucose-stimulated insulin secretion. The insulin action upon the glucose uptake by skeletal muscle was determined by means of hindquarter perfusions. Compared with control rats, magnesium-deficient rats presented: 1) normal basal glucose uptake, 2) lower stimulatory effect on the glucose uptake by insulin at the concentrations of 5 x 10(-10) mol/l (3.0 +/- 0.9 vs 5.4 +/- 0.6, p < 0.05) and 5 x 10(-9) mol/l (6.3 +/- 0.5 vs 8.0 +/- 0.5, p < 0.05), 3) normal glucose uptake at a maximal insulin concentration of 1 x 10(-7) mol/l, and 4) 50% reduction in the insulin sensitivity (ED50: 1.3 +/- 0.3 vs 0.55 +/- 0.1 mol/l, p < 0.05). In partially purified insulin receptors prepared from gastrocnemius muscle, 125I-insulin binding was similar in both groups of rats. However, the autophosphorylation of the beta-subunit of the insulin receptor was significantly reduced by 50% in magnesium-deficient rats and the tyrosine kinase activity of insulin receptors toward the exogenous substrate Poly Glu4; Tyr 1 was also reduced (p < 0.05) by hypomagnesaemia. The abundance of the insulin-sensitive glucose transporter protein (muscle/fat GLUT4), measured by Western blot analysis using polyclonal antisera, was similar in muscles of control and hypomagnesaemic rats. These findings indicate that hypomagnesaemia has a deleterious effect on glucose metabolism due to an impairment of both insulin secretion and action. The insulin resistance observed in skeletal muscle of magnesium-deficient rats may be attributed, at least in part, to a defective tyrosine kinase activity of insulin receptors.

Effect of Tree Nuts on Glycemic Control in Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Dietary Trials

“…Meta-analyses of prospective cohort studies and randomized double-blind controlled trials looking at magnesium intake in individuals with type 2 diabetes support decreases in diabetes risk [48], [49], as well as benefits for glycemic control [50]. Magnesium is thought to play a key role in insulin-mediated glucose uptake [51], [52], where animal studies have shown poor intracellular magnesium concentrations to result in defective tyrosine-kinase activity at the insulin-receptor level and therefore impairing insulin action [52], [53]. Similarly, in a meta-analysis of randomized controlled trials looking at the effects of MUFA on glycemic control in individuals with abnormal glucose metabolism, diets high in MUFA were shown to significantly reduce HbA1c [54].…”

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“…Magnesium plays a significant role in glucose and insulin metabolism, mainly through its impact on tyrosine kinase enzyme, magnesium may directly affect Glucose Transporter protein activity 4 and regulate glucose translocation into the cell. [19] …”

Protective mechanisms of the Mediterranean diet in obesity and type 2 diabetes

“…Reduced intracellular magnesium concentrations lead to a decrease in the activity of these enzymes, which, in turn, might favor insulin resistance. It has been shown that insulin resistance in magnesium-deficient rats might be partially attributed to a decrease of tyrosine kinase activity of insulin receptors [117]. At the extracellular level, magnesium moderates intracellular calcium uptake through its nonspecific antagonistic effects on calcium channels [118,119].…”