Protein kinase B activity is required for the effects of insulin on lipid metabolism in adipocytes.
Berggreen, Christine LU ; Gormand, Amelie LU ; Omar, Bilal LU ; Degerman, Eva LU
and Göransson, Olga
LU
(2009)
In American Journal of Physiology: Endocrinology and Metabolism
296.
p.635-646
- Abstract
- Protein kinase B is known to mediate a number of biological responses to insulin and growth factors, its role in glucose uptake being one of the most extensively studied. In this paper, we have employed a recently described allosteric inhibitor of PKB, Akti, to clarify the role of PKB in lipid metabolism in adipocytes - a subject that has received less attention. Pretreatment of primary rat and 3T3L1 adipocytes with Akti resulted in dose-dependent inhibition of PKB phosphorylation and activation in response to insulin, without affecting upstream insulin signaling (IR, IRS) or the insulin-induced PI3-K dependent activation of the ERK/RSK pathway. PKB activity was required for the insulin-induced activation of PDE3B and for the... (More)
- Protein kinase B is known to mediate a number of biological responses to insulin and growth factors, its role in glucose uptake being one of the most extensively studied. In this paper, we have employed a recently described allosteric inhibitor of PKB, Akti, to clarify the role of PKB in lipid metabolism in adipocytes - a subject that has received less attention. Pretreatment of primary rat and 3T3L1 adipocytes with Akti resulted in dose-dependent inhibition of PKB phosphorylation and activation in response to insulin, without affecting upstream insulin signaling (IR, IRS) or the insulin-induced PI3-K dependent activation of the ERK/RSK pathway. PKB activity was required for the insulin-induced activation of PDE3B and for the anti-lipolytic action of insulin. Moreover, inhibition of PKB activity resulted in a reduction in de novo lipid synthesis and in the ability of insulin to stimulate this process. The regulation of the rate-limiting lipogenic enzyme ACC by insulin through dephosphorylation of S79, which is a target for AMPK, was dependent on the presence of active PKB. Lastly, AMPK was shown to be phosphorylated by PKB on S485 in response to insulin and this was associated with a reduction in AMPK activity. In summary, we propose that PKB is required for the positive effects of insulin on lipid storage, and that regulation of PDE3B and AMPK by PKB is important for these effects. Key words: Akt, PDE3B, ACC, AMPK, lipogenesis. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1289424
- author
- Berggreen, Christine
LU
; Gormand, Amelie
LU
; Omar, Bilal
LU
; Degerman, Eva
LU
and Göransson, Olga
LU
- organization
- publishing date
- 2009
- type
- Contribution to journal
- publication status
- published
- subject
- in
- American Journal of Physiology: Endocrinology and Metabolism
- volume
- 296
- pages
- 635 - 646
- publisher
- American Physiological Society
- external identifiers
-
- wos:000264514900009
- pmid:19158325
- scopus:65649091377
- pmid:19158325
- ISSN
- 1522-1555
- DOI
- 10.1152/ajpendo.90596.2008
- language
- English
- LU publication?
- yes
- id
- a32b8e30-c42a-4875-893a-4b0c8de02b2a (old id 1289424)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/19158325?dopt=Abstract
- date added to LUP
- 2016-04-04 09:15:33
- date last changed
- 2024-02-28 00:57:36
@article{a32b8e30-c42a-4875-893a-4b0c8de02b2a,
abstract = {{Protein kinase B is known to mediate a number of biological responses to insulin and growth factors, its role in glucose uptake being one of the most extensively studied. In this paper, we have employed a recently described allosteric inhibitor of PKB, Akti, to clarify the role of PKB in lipid metabolism in adipocytes - a subject that has received less attention. Pretreatment of primary rat and 3T3L1 adipocytes with Akti resulted in dose-dependent inhibition of PKB phosphorylation and activation in response to insulin, without affecting upstream insulin signaling (IR, IRS) or the insulin-induced PI3-K dependent activation of the ERK/RSK pathway. PKB activity was required for the insulin-induced activation of PDE3B and for the anti-lipolytic action of insulin. Moreover, inhibition of PKB activity resulted in a reduction in de novo lipid synthesis and in the ability of insulin to stimulate this process. The regulation of the rate-limiting lipogenic enzyme ACC by insulin through dephosphorylation of S79, which is a target for AMPK, was dependent on the presence of active PKB. Lastly, AMPK was shown to be phosphorylated by PKB on S485 in response to insulin and this was associated with a reduction in AMPK activity. In summary, we propose that PKB is required for the positive effects of insulin on lipid storage, and that regulation of PDE3B and AMPK by PKB is important for these effects. Key words: Akt, PDE3B, ACC, AMPK, lipogenesis.}},
author = {{Berggreen, Christine and Gormand, Amelie and Omar, Bilal and Degerman, Eva and Göransson, Olga}},
issn = {{1522-1555}},
language = {{eng}},
pages = {{635--646}},
publisher = {{American Physiological Society}},
series = {{American Journal of Physiology: Endocrinology and Metabolism}},
title = {{Protein kinase B activity is required for the effects of insulin on lipid metabolism in adipocytes.}},
url = {{http://dx.doi.org/10.1152/ajpendo.90596.2008}},
doi = {{10.1152/ajpendo.90596.2008}},
volume = {{296}},
year = {{2009}},
}