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Diabetologia

, Volume 38, Issue 11, pp 1262–1270 | Cite as

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

  • A. Suárez
  • N. Pulido
  • A. Casla
  • B. Casanova
  • F. J. Arrieta
  • A. Rovira
Originals

Summary

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±0.2 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 5×10−10 mol/l (3.0±0.9 vs 5.4±0.6, p<0.05) and 5×10−9mol/l (6.3±0.5 vs 8.0±0.5, p<0.05), 3) normal glucose uptake at a maximal insulin concentration of 1×10−7 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 Β-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.

Key words

Magnesium insulin receptors tyrosine kinase skeletal muscle insulin secretion glucose disposal GLUT 4 

Abbreviations

WGA

Wheat germ agglutinin agarose

Hepes

N-2-hydroxyethylpiperazine-N′-2-ethane sulphonic acid

PMSF

phenylmethylsulphonyl fluoride

TBS

Tris buffered saline

IVGTT

intravenous glucose tolerance test

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Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • A. Suárez
    • 1
  • N. Pulido
    • 1
  • A. Casla
    • 1
  • B. Casanova
    • 1
  • F. J. Arrieta
    • 1
  • A. Rovira
    • 1
  1. 1.Department of Endocrinology, Fundación Jiménez DíazUniversidad Autónoma de MadridMadridSpain

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