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Diabetologia

, Volume 45, Issue 8, pp 1128–1135 | Cite as

Insulin signal transduction and glucose transport in human adipocytes: effects of obesity and low calorie diet

  •  M. Björnholm
  •  L. Al-Khalili
  •  A. Dicker
  •  E. Näslund
  •  S. Rössner
  •  J. Zierath
  •  P. Arner
Article

Heading

Abstract

Aim/hypothesis. We examined insulin signal transduction at the level of insulin receptor substrates (IRS) 1 and 2, phosphatidylinositol (PI) 3-kinase and glucose transport in isolated subcutaneous adipocytes from obese and lean women.

Methods. Glucose transport and insulin signalling were investigated in isolated adipocytes from six obese women (BMI 36–43 kg/m2) (before and after 11 days of very low calorie diet) and from six lean women (BMI 22–26 kg/m2).

Results. Insulin sensitivity of glucose transport was reduced in adipocytes from obese women (p<0.05), with further reductions in basal and maximal insulin-stimulated glucose transport after a very low calorie diet (p<0.05). In obese women, IRS-1 associated PI 3-kinase activity was markedly impaired (p<0.05), whereas, IRS-2 associated PI 3-kinase activity was normal. IRS-1 associated PI 3-kinase activity remained blunted after a very low calorie diet, whereas IRS-2 associated PI 3-kinase activity was increased. GLUT4 protein was reduced by 37% in obese versus lean subjects (p<0.05), and decreased further after a very low calorie diet (from 19±4 to 14±4 arbitrary units; p<0.05).

Conclusion/interpretation. IRS-1 signalling to PI 3-kinase is a site of insulin resistance in adipocytes from obese women, whereas insulin action on IRS-2 is normal. Thus, IRS-1 and IRS-2 undergo differential regulation in adipocytes from obese insulin resistant subjects. Finally, a very low calorie diet is associated with a further impairment in glucose transport in adipose tissue. The defect in glucose transport after a very low calorie diet occurs independent of further defects in insulin signalling at the level of the PI 3-kinase.

Insulin receptor insulin receptor substrates PI 3-kinase glucose transport GLUT4 

Copyright information

© Springer-Verlag 2002

Authors and Affiliations

  •  M. Björnholm
    • 2
  •  L. Al-Khalili
    • 2
  •  A. Dicker
    • 3
  •  E. Näslund
    • 4
  •  S. Rössner
    • 5
  •  J. Zierath
    • 1
  •  P. Arner
    • 3
  1. 1.Karolinska Institutet, Integrative Physiology, von Eulers väg 4, II, 171 77 Stockholm, Sweden
  2. 2.Department of Clinical Physiology, Karolinska Hospital, Stockholm, Sweden
  3. 3.Medicine and Clinical Research Centre at Huddinge University Hospital, Stockholm, Sweden
  4. 4.Division of Surgery, Karolinska Institutet Danderyd Hospital, Stockholm, Sweden
  5. 5.Obesity Unit at Huddinge University Hospital, Stockholm, Sweden

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