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  • 1
    ISSN: 1432-2307
    Keywords: Breast carcinoma ; ERBB2 ; E-cadherin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A recent in vitro study has suggested that overexpression of ERBB2 may mediate breast tumour progression and metastasis by inhibiting the transcription of the E-cadherin (E-CD) gene. To test this hypothesis in human breast cancer in vivo, we studied the relationship between the expression of both molecules in 247 breast carcinomas immunohistochemically. Five ductal carcinomas in situ overexpressed ERBB2 and showed preserved E-CD expression. Forty-four of 226 infiltrating ductal carcinomas (19.47%) showed ERBB2 overexpression, and a statistically significant relationship was found between ERBB2 overexpression and high histological grade. E-CD expression was preserved in 111 cases (49.1%) and correlated with the histological grade. However, no significant relationship was found between ERBB2 and E-CD expression. None of the 16 infiltrating lobular carcinomas expressed ERBB2 or E-CD. These observations in different histological types of breast carcinoma strongly argue against a role for ERBB2 as a transcriptional regulator of E-CD expression in most human breast carcinomas in vivo.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Magnesium ; insulin receptors ; tyrosine kinase ; skeletal muscle ; insulin secretion ; glucose disposal ; GLUT 4
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Key words Magnesium ; insulin receptors ; tyrosine kinase ; skeletal muscle ; insulin secretion ; glucose disposal ; GLUT 4.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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 × 10−9 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 × 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. [Diabetologia (1995) 38: 1262–1270]
    Type of Medium: Electronic Resource
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