Impaired tyrosine-kinase activity of muscle insulin receptors from hypomagnesaemic rats.
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.
Suárez
A
A
Department of Endocrinology, Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Spain.
Pulido
N
N
Casla
A
A
Casanova
B
B
Arrieta
F J
FJ
Rovira
A
A
D000818:Animals; D005947:Glucose / Q000493:pharmacokinetics; D007328:Insulin / Q000378:metabolism; D008275:Magnesium Deficiency / Q000378:metabolism*; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000378:metabolism*
D007328:Insulin; D009004:Monosaccharide Transport Proteins; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin; D005947:Glucose