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  • 1
    Electronic Resource
    Electronic Resource
    Impaired phosphorylation and insulin-stimulated translocation to the plasma membrane of protein kinase B/Akt in adipocytes from Type II diabetic subjects (2000)
    Springer
    Diabetologia 43 (2000), S. 1107-1115 
    Details
    ISSN: 1432-0428
    Keywords: Keywords PKB/Akt ; PI3-kinase ; insulin action ; Type II diabetes ; GLUT-4.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. To examine protein kinase B/Akt distribution and phosphorylation in response to insulin in different subcellular fractions of human fat cells from healthy subjects and subjects with Type II (non-insulin-dependent) diabetes mellitus. Methods. We prepared subcellular fractions of plasma membranes (PM), low density microsomes and cytosol and examined gene and protein expression as well as serine and threonine phosphorylation in response to insulin. Results. Protein kinase B/Akt mRNA as well as total protein kinase B/Akt protein in whole-cell lysate and cytosol were similar in both groups. Insulin increased protein kinase B/Akt translocation to the the plasma membrane about twofold [(p 〈 0.03) in non-diabetic cells but this effect was impaired in diabetic cells (∼ 30 %; p 〉 0.1)]. In both groups, protein kinase B/Akt threonine phosphorylation considerably increased in low density microsomes and cytosol whereas serine phosphorylation was predominant in the plasma membrane. Phosphatidylinositol-dependent kinase 1, which partially activates and phosphorylates protein kinase B/Akt on the specific threonine site, was predominant in cytosol but it was also recovered in low density microsomes. Serine phosphorylation in response to insulin was considerably reduced (50–70 %; p 〈 0.05) in diabetic cells but threonine phosphorylation was less reduced (∼ 20 %). Wortmannin inhibited these effects of insulin supporting a role for PI3-kinase activation. Conclusion/interpretation. Insulin stimulates a differential subcellular pattern of phosphorylation of protein kinase B/Akt. Furthermore, insulin-stimulated translocation of protein kinase B/Akt to the plasma membrane, where serine phosphorylation and full activation occurs, is impaired in Type II diabetes. Threonine phosphorylation was much less reduced. This discrepancy may be related to differential activation of phosphatidylinositol 3-kinase in the different subcellular compartments and phosphatidylinositol-dependent kinase 1 having high affinity for phosphatidylinositol phosphate 3. [Diabetologia (2000) 43: 1107–1115]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250051501
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Impaired glucose transport and protein kinase B activation by insulin, but not okadaic acid, in adipocytes from subjects with Type II diabetes mellitus (1999)
    Springer
    Diabetologia 42 (1999), S. 819-825 
    Details
    ISSN: 1432-0428
    Keywords: Keywords PKB ; insulin ; okadaic acid ; Type II diabetes ; glucose transport.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. To study the effects of insulin and okadaic acid, a serine/threonine phosphatase inhibitor which does not increase PI3-kinase activity, on the rate of glucose transport and protein kinase B activation in adipocytes from healthy subjects and subjects with Type II (non-insulin-dependent) diabetes mellitus. Methods. Adipocytes were incubated with or without insulin or okadaic acid or both and glucose transport, protein kinase B activity, phosphorylation and protein expression measured. Results. Insulin and okadaic acid alone increased glucose uptake to a similar degree in adipocytes from healthy subjects and, when combined, exerted a partial additive effect. The effect of insulin was reduced by about 60 % in adipocytes from Type II diabetic patients, whereas the effect of okadaic acid was essentially unchanged and no further increase was seen when okadaic acid and insulin were combined. Okadaic acid increased protein kinase B activity to a greater extent (two to threefold) than insulin but only slightly increased the serine phosphorylation of protein kinase B. Adipocytes from Type II diabetic subjects exhibited both an impaired sensitivity as well as a reduced total serine phosphorylation and activation of protein kinase B in response to insulin but protein kinase B activity in response to okadaic acid was intact. Conclusion/interpretation. These results show that the ability of insulin to increase glucose transport and activate protein kinase B is reduced in fat cells from Type II diabetic subjects. Protein kinase B can, however, be activated by agents like okadaic acid which bypass the upstream defects in the insulin signalling pathway in Type II diabetic cells and, thus, increase glucose uptake. [Diabetologia (1999) 42: 819–825]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250051232
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    Paper (German National Licenses)
    Fulltext
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