Diabetologia

, Volume 42, Issue 7, pp 819–825 | Cite as

Impaired glucose transport and protein kinase B activation by insulin, but not okadaic acid, in adipocytes from subjects with Type II diabetes mellitus

  • C. M. Rondinone
  • E. Carvalho
  • C. Wesslau
  • U. P. Smith
Rapid communication

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]

Keywords PKB insulin okadaic acid Type II diabetes glucose transport. 

Copyright information

© Springer-Verlag Berlin Heidelberg 1999

Authors and Affiliations

  • C. M. Rondinone
    • 1
  • E. Carvalho
    • 1
  • C. Wesslau
    • 1
  • U. P. Smith
    • 1
  1. 1.The Lundberg Laboratory for Diabetes Research, Department of Internal Medicine, Sahlgrenska University Hospital, Gothenburg, SwedenSE

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