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Dimethylaminopurine inhibits metabolic effects of insulin in primary adipocytes.

Göransson, Olga LU ; Rydén, Mikael; Nilsson, Rebecka; Arner, Peter and Degerman, Eva LU (2004) In Journal of Nutritional Biochemistry 15(5). p.303-312
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Antilipolysis, DMAP, PKB, JNK, Insulin, Adipocyte
in
Journal of Nutritional Biochemistry
volume
15
issue
5
pages
303 - 312
publisher
Elsevier
external identifiers
  • wos:000221561100008
  • scopus:2342576717
ISSN
1873-4847
DOI
10.1016/j.jnutbio.2004.01.004
language
English
LU publication?
yes
id
1eb4c7c4-7e59-41ae-85d5-9bd24de82c0c (old id 123543)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15135155&dopt=Abstract
date added to LUP
2007-07-12 15:03:41
date last changed
2017-01-01 07:08:25
@article{1eb4c7c4-7e59-41ae-85d5-9bd24de82c0c,
  abstract     = {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.<br/><br>
<br/><br>
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.<br/><br>
<br/><br>
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.},
  author       = {Göransson, Olga and Rydén, Mikael and Nilsson, Rebecka and Arner, Peter and Degerman, Eva},
  issn         = {1873-4847},
  keyword      = {Antilipolysis,DMAP,PKB,JNK,Insulin,Adipocyte},
  language     = {eng},
  number       = {5},
  pages        = {303--312},
  publisher    = {Elsevier},
  series       = {Journal of Nutritional Biochemistry},
  title        = {Dimethylaminopurine inhibits metabolic effects of insulin in primary adipocytes.},
  url          = {http://dx.doi.org/10.1016/j.jnutbio.2004.01.004},
  volume       = {15},
  year         = {2004},
}