Suárez A, Pulido N, Casla A, Casanova B, Arrieta F J, Rovira A
Department of Endocrinology, Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Spain.
Diabetologia. 1995 Nov;38(11):1262-70. doi: 10.1007/BF00401757.
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.
研究了缺镁对大鼠葡萄糖代谢、葡萄糖刺激的胰岛素分泌以及胰岛素对骨骼肌作用的影响。将大鼠喂食低镁饮食4天，对照组大鼠喂食标准饮食。与对照组大鼠相比，喂食低镁饮食的大鼠表现为：1）血清镁水平较低（0.45±0.02 vs 0.78±0.01 mmol/l，p<0.001）；2）基础血清葡萄糖水平较高（6.8±0.02 vs 5.5±0.2 mmol/l，p<0.05），基础血清胰岛素水平相似；3）静脉注射葡萄糖后葡萄糖消失率降低40%（p<0.001）；4）葡萄糖刺激的胰岛素分泌降低45%（p<0.05）。通过后肢灌注法测定胰岛素对骨骼肌摄取葡萄糖的作用。与对照组大鼠相比，缺镁大鼠表现为：1）基础葡萄糖摄取正常；2）在5×10⁻¹⁰ mol/l（3.0±0.9 vs 5.4±0.6，p<0.05）和5×10⁻⁹ mol/l（6.3±0.5 vs 8.0±0.5，p<0.05）浓度下，胰岛素对葡萄糖摄取的刺激作用较低；3）在最大胰岛素浓度1×10⁻⁷ mol/l时葡萄糖摄取正常；4）胰岛素敏感性降低50%（ED50：1.3±0.3 vs 0.55±0.1 mol/l，p<0.05）。在从腓肠肌制备的部分纯化胰岛素受体中，两组大鼠的¹²⁵I-胰岛素结合相似。然而，缺镁大鼠胰岛素受体β亚基的自磷酸化显著降低50%，低镁血症也使胰岛素受体对外源底物聚谷氨酸4；酪氨酸1的酪氨酸激酶活性降低（p<0.05）。使用多克隆抗血清通过蛋白质印迹分析测定的胰岛素敏感葡萄糖转运蛋白（肌肉/脂肪GLUT4）丰度，在对照组和低镁血症大鼠的肌肉中相似。这些发现表明，低镁血症由于胰岛素分泌和作用受损而对葡萄糖代谢产生有害影响。缺镁大鼠骨骼肌中观察到的胰岛素抵抗可能至少部分归因于胰岛素受体酪氨酸激酶活性缺陷。
