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  • 1
    ISSN: 1432-0428
    Keywords: Insulin receptor ; tyrosine kinase ; goldthioglucose obese mice ; insulin resistance ; muscle ; hyperinsulinaemia ; acarbose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of prolonged treatment with acarbose, an inhibitor of α-glycosidase, has been studied in mice made obese and hyperinsulinaemic by goldthioglucose. After the onset of obesity, one month after goldthioglucose administration, mice were then treated, with or without a 10% sucrose supplement, for four months with acarbose, added to the diet at 50 mg/100 g food. When mice received a standard diet, acarbose had no effect on body weight, blood glucose or insulin levels. In contrast, in the control obese mice receiving a 10% sucrose-enriched diet, it decreased the body weight gain, and prevented the rise in glycaemia and insulinaemia. Basal (non insulin-stimulated) glucose uptake, which is decreased in isolated soleus muscle from untreated obese mice, returned to normal values under acarbose treatment. However, muscle insulin resistance was not improved in acarbose-treated obese mice at maximal and submaximal effective concentrations, despite a higher insulin binding in muscles of acarbose-treated obese than in control obese animals. Furthermore, insulin receptor autophosphorylation and tyrosine kinase activity were altered similarly in treated and untreated obese mice compared to lean mice.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Insulin signalling ; MAP-kinase ; PI3-kinase ; IRS 1 ; GLUT 4 translocation ; insulin resistance ; wortmannin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Insulin-induced glucose transport stimulation, which results from the translocation of glucose transporter 4 (GLUT 4)-containing vesicles, is completely blocked after prolonged insulin treatment of 3T3-L1 adipocytes. Since GLUT 4 expression was reduced by only 30%, we looked at the insulin signalling pathway in this insulin-resistant model. Insulin-induced tyrosine phosphorylation of the major insulin receptor substrate IRS 1 was reduced by 50±7%, while its expression was decreased by 70±4%. When cells were treated with wortmannin (a PI3-kinase inhibitor) together with insulin, the expression of IRS 1 diminished to a much lower extent. Associated with the decrease in IRS 1 expression and phosphorylation, the activation by insulin of antiphosphotyrosine immunoprecipitable PI3-kinase activity and of p44mapk and p42mapk activities was altered. However, the expression of these proteins was normal and p44mapk activity remained responsive to the tumour promoter TPA. Those results indicate that prolonged insulin treatment of 3T3-L1 adipocytes induces an insulin-resistant state with a reduced ability of insulin to stimulate the PI3-kinase and the MAP-kinases and a blockade of glucose transporter translocation.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 14 (1978), S. 337-341 
    ISSN: 1432-0428
    Keywords: Injury ; insulin binding ; insulin resistance ; glucagon binding ; muscle
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Acute insulin resistance developed after scald injury in the mouse. After 2h plasma glucose and insulin concentrations were each raised about two-fold. Glucose metabolism was studied in vitro in soleus muscles isolated at this time. Glycolysis and glycogen synthesis, and their stimulation by insulin, were unchanged in muscles from scalded mice, and insulin-stimulated transport of 2-deoxyglucose slightly increased, showing that the insulin resistance seen in vivo is not maintained in isolated tissues. Binding of insulin to liver cell membranes prepared from scalded mice was unaltered, whilst that of glucagon was slightly but significantly reduced, showing that changes in polypeptide-hormone receptors can occur within this short time. It was concluded that the acute loss of sensitivity to insulin after injury does not result from a change in insulin receptor sites and presumably reflects an impairment of glucose metabolism in vivo mediated by circulating hormones.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0428
    Keywords: Anti-insulin receptor antibodies ; insulin-like effects ; insulin resistance ; skeletal muscle ; insulin receptor ; insulin binding ; insulin action ; glucose transport ; glycolysis ; glycogen synthesis ; obese mice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Autoantibodies against the insulin receptor are found in the serum of some patients with severe insulin resistance. The effects of one of these sera on insulin binding and on glucose transport and metabolism were investigated in the isolated mouse soleus muscle. Preincubation of muscles with the patient's serum resulted in an inhibition of subsequent125I-insulin binding (half-maximal effect at 1∶500 dilution) and in a two to three-fold stimulation of glucose transport and metabolism (half-maximal effect at 1∶2000 dilution). The insulin-like effects were blocked by anti-human IgG, but not by antiinsulin antibodies. The magnitude of the serum effects on 2-deoxyglucose uptake and glycolysis was similar to that of insulin, but the effect on glycogen synthesis was smaller than that of insulin. It is suggested that the patient's serum and insulin promote glucose transport and glycolysis through a common pathway, but act differently on glycogen synthesis.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0428
    Keywords: Key words Insulin signalling ; MAP-kinase ; PI3-kinase ; IRS 1 ; GLUT 4 translocation ; insulin resistance ; wortmannin.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Insulin-induced glucose transport stimulation, which results from the translocation of glucose transporter 4 (GLUT 4)-containing vesicles, is completely blocked after prolonged insulin treatment of 3T3-L1 adipocytes. Since GLUT 4 expression was reduced by only 30 %, we looked at the insulin signalling pathway in this insulin-resistant model. Insulin-induced tyrosine phosphorylation of the major insulin receptor substrate IRS 1 was reduced by 50 ± 7 %, while its expression was decreased by 70 ± 4 %. When cells were treated with wortmannin (a PI3-kinase inhibitor) together with insulin, the expression of IRS 1 diminished to a much lower extent. Associated with the decrease in IRS 1 expression and phosphorylation, the activation by insulin of antiphosphotyrosine immunoprecipitable PI3-kinase activity and of p44mapk and p42mapk activities was altered. However, the expression of these proteins was normal and p44mapk activity remained responsive to the tumour promoter TPA. Those results indicate that prolonged insulin treatment of 3T3-L1 adipocytes induces an insulin-resistant state with a reduced ability of insulin to stimulate the PI3-kinase and the MAP-kinases and a blockade of glucose transporter translocation. [Diabetologia (1995) 38: 1148–1156]
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 28 (1985), S. 295-301 
    ISSN: 1432-0428
    Keywords: Insulin ; insulin resistance ; obesity ; exercise ; glucose metabolism ; glycogen synthase ; fructose 2–6 bisphosphate ; skeletal muscle ; goldthioglucose obese mice ; hypertrophy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of work-induced hypertrophy (without any concomitant change in circulating parameters) on skeletal muscle metabolism was studied in lean mice and in goldthioglucose obese-mice. Soleus muscle was functionally overloaded in one leg by tenotomy of gastrocnemius muscle 4 days before muscle isolation, muscle in the other leg being used as control. Basal deoxyglucose uptake and glycolysis were markedly increased in overloaded muscles compared with control muscles, together with a ten-fold increase in fructose 2–6 bisphosphate content. In the presence of maximally effective insulin concentrations, deoxyglucose uptake and glycolysis were identical in overloaded and control muscles of lean mice, while the effects of overload and insulin were partly additive in muscles of goldthioglucose-obese mice. The sensitivity to insulin and insulin binding to muscles were not modified in overloaded muscles. Insulin-stimulated glycogenogenesis was decreased by about 50% probably due to a lower amount of glycogen synthase in overloaded than in control muscles. Thus, in muscles of goldthioglucose-obese mice work-induced hypertrophy increased the response to maximal insulin concentrations without modifying the altered insulin sensitivity and decreased insulin binding.
    Type of Medium: Electronic Resource
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