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  • 1
    Electronic Resource
    Electronic Resource
    Increased mitogen-activated protein kinase expression and activity in white adipose tissue of ventromedial hypothalamus-lesioned rats (1997)
    Springer
    Diabetologia 40 (1997), S. 533-540 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Insulin signalling ; MAP-kinase ; insulin receptor ; insulin sensitivity ; obesity ; white adipose tissue.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Ventromedial hypothalamus lesions in rats induce hyperphagia and hyperinsulinaemia associated with a rapid growth of white adipose tissue resulting in massive obesity. It has been shown previously that at an early stage after the lesion, during the dynamic phase of obesity, the white adipose tissue is hyper-responsive to insulin. In the present work, we show that the effects of insulin on the autophosphorylation of the insulin receptor and on its tyrosine-kinase activity towards endogenous substrates are similar in intact adipocytes of control and ventromedial hypothalamus lesioned rats. One week after the lesion, the expression of phosphatidylinisitol 3-kinase and RAF-1 kinase, evaluated by Western-blotting, was similar in control and ventromedial hypothalamus lesioned rats. In contrast, an important increase in the expression of extracellular signal regulated kinase 1 protein was observed in white adipose tissue of ventromedial hypothalamus lesioned compared to control animals. No difference in the expression of extracellular signal regulated kinase 1 mRNA was observed in adipose tissue of control and ventromedial hypothalamus lesioned rats, suggesting that a post-transcriptional mechanism is involved in the over-expression of extracellular signal regulated kinase 1. The kinase activity of extracellular signal regulated kinase 1 and 2 is also markedly increased in adipocytes of ventromedial hypothalamus lesioned compared to control rats, both in the basal state and after insulin stimulation. Six weeks after the ventromedial hypothalamus lesion, this increase in mitogen-activated protein kinase expression and activity was still observed in adipocytes of ventromedial hypothalamus lesioned rats. These results suggest that an early and sustained increase in the expression and activity of mitogen-activated protein kinase may participate in the development of white adipose tissue in ventromedial hypothalamus lesioned rats. [Diabetologia (1997) 40: 533–540]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250050712
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  • 2
    Electronic Resource
    Electronic Resource
    In vivo and in vitro increased pancreatic beta-cell sensitivity to glucose in normal rats submitted to a 48-h hyperglycaemic period (1993)
    Springer
    Diabetologia 36 (1993), S. 589-595 
    Details
    ISSN: 1432-0428
    Keywords: Glucose infusion ; in vivo insulin secretion ; in vitro insulin secretion ; beta-cell sensitivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We investigated the importance of the level and the duration of glucose stimulation on the in vivo and in vitro insulin response to glucose in normal rats previously submitted to hyperglycaemia. Rats were made hyperglycaemic by a 48-h glucose infusion. Glucose-induced insulin secretion was investigated in vivo by a 20-min hyperglycaemic clamp and in vitro by the isolated perfused pancreas technique, 3 h after the end of the in vivo glucose infusion. In glucose-infused rats, as compared to controls, in vivo incremental plasma insulin values above baseline integrated over the 20-min hyperglycaemic clamp (ΔI) were five times higher during 8 mmol/l glucose clamp, only two times higher in 11 mmol/l glucose clamp and no different in 16.5 mmol/l. Compared to the controls, in vitro incremental plasma insulin concentration above baseline integrated over a 20-min period (ΔI) in glucose-infused rats was 16 times higher in response to 2.8 mmol/l glucose, two times higher in response to 5.5 mmol/l, similar in response to 8.3 mmol/l and significantly lower in response to 16.5 mmol/l. In conclusion, our data suggest that a 48-h hyperglycaemic period results in an increased response of the pancreatic beta cell to low glucose. The response is immediately maximal and can not be increased with higher glucose concentrations. This situation could explain the apparent minimal effect of high concentrations on in vitro insulin secretion in previously hyperglycaemic rats and may provide insights into the sequence of events leading to the impairment of beta-cell function in Type 2 (non-insulin-dependent) diabetes mellitus.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00404066
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
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