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Eva Degerman

Eva Degerman

Professor

Eva Degerman

Dimethylaminopurine inhibits metabolic effects of insulin in primary adipocytes.

Author

  • Olga Göransson
  • Mikael Rydén
  • Rebecka Nilsson
  • Peter Arner
  • Eva Degerman

Summary, in English

Dimethylaminopurine (DMAP) has previously been used as an inhibitor of phosphorylation in studies of meiotic events, and more recently to investigate TNFα signaling, because of its potential to inhibit activation of c-jun N-terminal kinase (JNK). Here we have addressed the effects of DMAP on metabolic insulin responses in adipocytes and on intracellular insulin signaling molecules.



At 100 μmol/L, DMAP completely inhibited the ability of insulin to counteract lipolysis in isolated adipocytes. Insulin-induced lipogenesis and glucose uptake was inhibited to a lesser degree in a concentration-dependent manner starting at 10 μmol/L DMAP. Insulin-induced tyrosine phosphorylation of the insulin receptor was not affected by DMAP. Insulin-induced activation of protein kinase B, a known mediator of insulin action, was not inhibited by 100 μmol/L, but to a low extent by 1 mmol/L DMAP in intact cells. This inhibition was not sufficient to affect activation of the downstream protein kinase B substrate phosphodiesterase 3B.



The inhibition of activation of JNK as a possible mechanism whereby DMAP affects insulin-induced antilipolysis, lipogenesis, and glucose uptake, was investigated using the JNK inhibitor SP600125. At 100 μmol/L, SP600125 completely reversed the antilipolytic effect of insulin, as well as partially inhibited insulin-induced lipogenesis and glucose-uptake, indicating that JNK may be involved in mediating these actions of insulin. Inhibition of JNK by DMAP may therefore partly explain the negative impact of DMAP on insulin action in adipocytes.

Department/s

  • Insulin Signal Transduction
  • Protein Phosphorylation

Publishing year

2004

Language

English

Pages

303-312

Publication/Series

Journal of Nutritional Biochemistry

Volume

15

Issue

5

Document type

Journal article

Publisher

Elsevier

Topic

  • Nutrition and Dietetics

Keywords

  • Antilipolysis
  • DMAP
  • PKB
  • JNK
  • Insulin
  • Adipocyte

Status

Published

Research group

  • Insulin Signal Transduction
  • Protein Phosphorylation

ISBN/ISSN/Other

  • ISSN: 1873-4847