Protein kinase B activity is required for the effects of insulin on lipid metabolism in adipocytes
Open accessAbstract
Protein kinase B (PKB) 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 work, 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 [insulin receptor (IR), insulin receptor substrate (IRS)] or the insulin-induced phosphoinositide 3-kinase (PI3K)-dependent activation of the ERK/p90 ribosomal kinase (RSK) pathway. PKB activity was required for the insulin-induced activation of phosphodiesterase 3B (PDE3B) and for the antilipolytic 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 acetyl-CoA carboxylase (ACC) by insulin through dephosphorylation of S79, which is a target for AMP-activated protein kinase (AMPK), was dependent on the presence of active PKB. Finally, 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.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
AMPK regulates IRS-1 and Akt/PKB, whereas insulin and Akt have negative impacts on AMPK activation in adipocytes.
“It has been reported that AMPK regulates IRS-1 and Akt/PKB (23), whereas insulin and Akt have negative impacts on AMPK activation in adipocytes (6).”
From Hypoglycemic effects of brassinosteroid in diet-induced obese mice (2012) · cites this paper as [6]
Cites
Bradford, M. M. (1976) · Analytical Biochemistry · doi:10.1016/0003-2697(76)90527-3 · Cited by 255,302 · see citing works
Metabolism of Isolated Fat Cells
Rodbell, M. (1964) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)51687-2 · Cited by 4,647 · see citing works
Cellular survival: a play in three Akts
Datta, S. R., Brunet, A., & Greenberg, M. E. (1999) · Genes & Development · doi:10.1101/gad.13.22.2905 · Cited by 4,216 · see citing works
Alessi, D., James, S., Downes, C., Holmes, A. B., Gaffney, P., Reese, C., & Cohen, P. (1997) · Current Biology · doi:10.1016/s0960-9822(06)00122-9 · Cited by 3,047 · see citing works
Mechanism of activation of protein kinase B by insulin and IGF‐1.
Alessi, D. R., Andjelković, M., Caudwell, B., Cron, P. D., MORRICE, N. A., Cohen, P., & Hemmings, B. A. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb01045.x · Cited by 2,985 · see citing works
Kohn, A. D., Summers, S. A., Birnbaum, M. J., & Roth, R. A. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.49.31372 · Cited by 1,284 · see citing works
Continuous fatty acid oxidation and reduced fat storage in mice lacking acetyl-CoA carboxylase 2
Abu-Elheiga, L., Matzuk, M. M., Abo-Hashema, K. A. H., & Wakil, S. J. (2001) · Science · doi:10.1126/science.1056843 · Cited by 903 · see citing works
Advances in protein kinase B signalling: AKTion on multiple fronts
Brazil, D. P., Yang, Z., & Hemmings, B. A. (2004) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2004.03.006 · Cited by 826 · see citing works
Role of Akt/protein kinase B in metabolism.
Whiteman, E. L., Cho, H., & Birnbaum, M. (2002) · Trends in endocrinology and metabolism · doi:10.1016/s1043-2760(02)00662-8 · Cited by 705 · see citing works
mTOR·RICTOR Is the Ser473 Kinase for Akt/Protein Kinase B in 3T3-L1 Adipocytes
Hresko, R. C., & Mueckler, M. M. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m508361200 · Cited by 631 · see citing works
Molecular Mechanisms Regulating Hormone-Sensitive Lipase and Lipolysis
Holm, C., Østerlund, T., Laurell, H., & Contreras, J. A. (2000) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.20.1.365 · Cited by 565 · see citing works
Role for Akt3/Protein Kinase Bγ in Attainment of Normal Brain Size
Easton, R., Cho, H., Roovers, K., Shineman, D. W., Mizrahi, M., Forman, M. S., Lee, V. M. ‐., Szabolcs, M. J., de Jong, R., Oltersdorf, T., et al. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.5.1869-1878.2005 · Cited by 551 · see citing works
Allosteric Akt (PKB) inhibitors: discovery and SAR of isozyme selective inhibitors
Lindsley, C. W., Zhao, Z., Leister, W., Robinson, R., Barnett, S. F., Defeo-Jones, D., Jones, R. E., Hartman, G. D., Huff, J. R., Huber, H. E., et al. (2004) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2004.11.011 · Cited by 504 · see citing works
Akt Activity Negatively Regulates Phosphorylation of AMP-activated Protein Kinase in the Heart
Kovacic, S., Soltys, C.-L. M., Barr, A., Shiojima, I., Walsh, K., & Dyck, J. R. B. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m305371200 · Cited by 407 · see citing works
Barnett, S. F., Defeo-Jones, D., Fu, S., Hancock, P. J., Haskell, K., Jones, R. E., Kahana, J. A., Kral, A. M., Leander, K. R., LEE, L. L., et al. (2005) · Biochemical Journal · doi:10.1042/bj20041140 · Cited by 398 · see citing works
REGULATION OF MAMMALIAN ACETYL-COENZYME A CARBOXYLASE
Kim, K.-H. (1997) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.17.1.77 · Cited by 394 · see citing works
The identification of ATP-citrate lyase as a protein kinase B (Akt) substrate in primary adipocytes
Berwick, D. C., Hers, I., Heesom, K. J., Moule, S. K., & Tavareá, J. M. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m204681200 · Cited by 383 · see citing works
Kitamura, T., Kitamura, Y., Kuroda, S., Hino, Y., Ando, M., Kotani, K., Konishi, H., Matsuzaki, H., Kikkawa, U., Ogawa, W., et al. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.9.6286 · Cited by 371 · see citing works
A Simple Free Fat Cell Bioassay for Insulin
Moody, A., Stan, M., Stan, M., & Gliemann, J. (1974) · Hormone and Metabolic Research · doi:10.1055/s-0028-1093895 · Cited by 363 · see citing works
Horman, S., Vertommen, D., Heath, R. B., Neumann, D., Mouton, V., Woods, A., Schlattner, U., Wallimann, T., Carling, D., Hue, L., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m506850200 · Cited by 345 · see citing works
Maurice, D. H., Palmer, D., Tilley, D. G., et al. (2003) · Molecular Pharmacology · doi:10.1124/mol.64.3.533 · Cited by 324 · see citing works
MUNDAY, M. R., CAMPBELL, D. G., CARLING, D., & HARDIE, D. G. (1988) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1988.tb14201.x · Cited by 308 · see citing works
Role of AMP-activated Protein Kinase in Cyclic AMP-dependent Lipolysis In 3T3-L1 Adipocytes
Wu, Y., Mu, J., & Birnbaum, M. J. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m308484200 · Cited by 287 · see citing works
Walker, K. S., Deák, M., PATERSON, A., Hudson, K., Cohen, P., & Alessi, D. R. (1998) · Biochemical Journal · doi:10.1042/bj3310299 · Cited by 279 · see citing works
DAVIES, S. P., SIM, A. T. R., & HARDIE, D. G. (1990) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1990.tb15293.x · Cited by 274 · see citing works
AMP-activated Protein Kinase Is Activated as a Consequence of Lipolysis in the Adipocyte
Gauthier, M., Miyoshi, H., Souza, S. C., Cacicedo, J. M., Saha, A. K., Greenberg, A. S., & Ruderman, N. B. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m708177200 · Cited by 245 · see citing works
The Adipose Tissue Phenotype of Hormone‐Sensitive Lipase Deficiency in Mice
Wang, S. P., Laurin, N., Himms‐Hagen, J., Rudnicki, M. A., Levy, E. H., Robert, M., Pan, L., Oligny, L. L., & Mitchell, G. A. (2001) · Obesity Research · doi:10.1038/oby.2001.15 · Cited by 236 · see citing works
Gonzalez, E., & McGraw, T. E. (2006) · Molecular Biology of the Cell · doi:10.1091/mbc.e06-07-0585 · Cited by 210 · see citing works
Effects of Lipolytic and Antilipolytic Agents on Cyclic 3',5'-Adenosine Monophosphate in Fat Cells
Manganiello, V. C., Murad, F., & Vaughan, M. M. (1971) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)77207-x · Cited by 197 · see citing works
Konishi, H., Kuroda, S., Tanaka, M., Matsuzaki, H., Ono, Y., Kameyama, K., Haga, T., & Kikkawa, U. (1995) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1995.2654 · Cited by 192 · see citing works
Insulin and the regulation of adipose-tissue acetyl-coenzyme A carboxylase
Halestrap, A. P., & Denton, R. M. (1973) · Biochemical Journal · doi:10.1042/bj1320509 · Cited by 189 · see citing works
Alterations in regulation of energy homeostasis in cyclic nucleotide phosphodiesterase 3B–null mice
Choi, Y. H., Park, S., Hockman, S. C., Zmuda‐Trzebiatowska, E., Svennelid, F., Haluzı́k, M., Gavrilova, O., Ahmad, F., Pepin, L., Napolitano, M., et al. (2006) · Journal of Clinical Investigation · doi:10.1172/jci24867 · Cited by 181 · see citing works
Self-citationDefeo-Jones, D., Barnett, S. F., Fu, S., Hancock, P. J., Haskell, K., Leander, K. R., McAvoy, E., Robinson, R., Duggan, M. E., Lindsley, C. W., et al. (2005) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.271.4.2 · Cited by 173 · see citing works
Esposito, D. L., Li, Y., Cama, A., & Quon, M. J. (2001) · Endocrinology · doi:10.1210/endo.142.7.8283 · Cited by 161 · see citing works
Taira, M., Hockman, S. C., Calvo, J. C., et al. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)46666-x · Cited by 138 · see citing works
Londos, C., Brasaemle, D. L., Gruia-Gray, J., et al. (1995) · Biochemical Society Transactions · doi:10.1042/bst0230611 · Cited by 132 · see citing works
Insulin stimulates the dephosphorylation and activation of acetyl-CoA carboxylase.
Witters, L. A., Watts, T. D., Daniels, D., & Evans, J. L. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.15.5473 · Cited by 114 · see citing works
The activation of p38 MAPK by the β‐adrenergic agonist isoproterenol in rat epididymal fat cells
MOULE, S. K., & Denton, R. M. (1998) · FEBS Letters · doi:10.1016/s0014-5793(98)01392-1 · Cited by 113 · see citing works
Green, C., Göransson, O., Kular, G. S., Leslie, N. R., Gray, A., Alessi, D. R., Sakamoto, K., & Hundal, H. S. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m802623200 · Cited by 113 · see citing works
Self-citationEriksson, H., Ridderstråle, M., Degerman, E., Ekholm, D., Smith, C. J., Manganiello, V. C., Belfrage, P., & Tornqvist, H. E. (1995) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/0167-4889(94)00237-9 · Cited by 113 · see citing works
Self-citationGaidhu, M. P., Fediuc, S., & Ceddia, R. B. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m602992200 · Cited by 108 · see citing works
Kerfant, B., Zhao, D., Lorenzen‐Schmidt, I., Wilson, L. S., Cai, S., Chen, S. R. W., Maurice, D. H., & Backx, P. H. (2007) · Circulation Research · doi:10.1161/circresaha.107.156422 · Cited by 106 · see citing works
Characterization of a Protein Kinase B Inhibitor In Vitro and in Insulin-Treated Liver Cells
Logie, L., Ruiz‐Alcaraz, A. J., Keane, M. P., Woods, Y. L., Bain, J., Márquez, R., Alessi, D. R., & Sutherland, C. D. (2007) · Diabetes · doi:10.2337/db07-0343 · Cited by 100 · see citing works
Acute hormonal control of acetyl-CoA carboxylase. The roles of insulin, glucagon, and epinephrine.
Mabrouk, G., Helmy, I., Thampy, K. G., et al. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)39330-5 · Cited by 91 · see citing works
Protein Kinase B/Akt Induces Resumption of Meiosis in Xenopus Oocytes
Andersen, C., Roth, R. A., & Conti, M. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.30.18705 · Cited by 85 · see citing works
Zmuda‐Trzebiatowska, E., Oknianska, A., Manganiello, V. C., et al. (2005) · Cellular Signalling · doi:10.1016/j.cellsig.2005.05.007 · Cited by 74 · see citing works
Haystead, T., Campbell, D. G., & Hardie, D. G. (1988) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1988.tb14203.x · Cited by 69 · see citing works
[Enzymic method for the determination of glycerin].
WIELAND, O. H. (1957) · PubMed · Cited by 69 · see citing works
Ahmad, F., Cong, L.-N., Holst, L. S., et al. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.164.9.4678 · Cited by 62 · see citing works
ANTILIPOLYTIC ACTION OF INSULIN: ROLE OF cAMP PHOSPHODIESTERASE ACTIVATION
Elks, M. L., & Manganiello, V. C. (1985) · Endocrinology · doi:10.1210/endo-116-5-2119 · Cited by 62 · see citing works
Smith, U., Carvalho, E., Mosialou, E., et al. (2000) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2000.2145 · Cited by 61 · see citing works
Barthel, A., Nakatani, K., Dandekar, A. A., & Roth, R. A. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.8134 · Cited by 50 · see citing works
Ahmad, F., Lindh, R., Tang, Y., et al. (2007) · Biochemical Journal · doi:10.1042/bj20060960 · Cited by 50 · see citing works
Ha, J., & Kim, K. H. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.21.9951 · Cited by 36 · see citing works
Zmuda‐Trzebiatowska, E., Manganiello, V. C., & Degerman, E. (2006) · Cellular Signalling · doi:10.1016/j.cellsig.2006.05.024 · Cited by 35 · see citing works
Self-citationEffect of insulin on association of acetyl CoA carboxylase phosphatase and acetyl CoA carboxylase
Krakower, G. R., & Kim, K.-H. (1985) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(85)90489-9 · Cited by 9 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
ROS signaling under metabolic stress: cross-talk between AMPK and AKT pathway
Zhao, Y., Hu, X., Liu, Y., Dong, S., Wen, Z., He, W., Zhang, S., Huang, Q., & Shi, M. (2017) · Molecular Cancer · doi:10.1186/s12943-017-0648-1 · Cited by 735 · see citing works
Rabot, S., Membrez, M., Bruneau, A., Gérard, P., Harach, T., Moser, M., Raymond, F., Mansourian, R., & Chou, C. J. (2010) · The FASEB Journal · doi:10.1096/fj.10.164921 · Cited by 610 · see citing works
Rabot, S., Membrez, M., Bruneau, A., Gérard, P., Harach, T., Moser, M., Raymond, F., Mansourian, R., & Chou, C. J. (2010) · The FASEB Journal · doi:10.1096/fj.10-164921 · Cited by 610 · see citing works
Signalling by insulin and IGF receptors: supporting acts and new players
Siddle, K. (2011) · Journal of Molecular Endocrinology · doi:10.1530/jme-11-0022 · Cited by 456 · see citing works
Metabolic control by AMPK in white adipose tissue
Göransson, O., Kopietz, F., & Rider, M. H. (2023) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2023.08.011 · Cited by 74 · see citing works
Self-citationJönsson, C., Castor Batista, A. P., Kjølhede, P., & Strålfors, P. (2019) · Biochemical Journal · doi:10.1042/bcj20190594 · Cited by 34 · see citing works
Zhang, X., Tian, L., Majumdar, A., & Scheller, E. L. (2024) · Comprehensive Physiology · doi:10.1002/j.2040-4603.2024.tb00300.x · Cited by 18 · see citing works
Hypoglycemic effects of brassinosteroid in diet-induced obese mice
Esposito, D., Kizelsztein, P., Komarnytsky, S., & Raskin, I. (2012) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00024.2012 · Cited by 14 · see citing works
- Authors
- Berggreen, C., Gormand, A., Omar, B., Degerman, E., & Göransson, O.
- Affiliations
- Lund University (SE)
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 2009-04
- Volume
- 296
- Issue
- 4
- Pages
- E635-E646
- ISSN
- 0193-1849 (ISSN-L)
- 1522-1555
- OpenAlex
- W2113517766
- Cited by
- 118
- References
- 56
- Citations by year
- 2026: 3 · 2024: 4 · 2023: 3 · 2022: 6 · 2021: 6 · 2020: 6 · 2019: 2 · 2018: 4 · 2017: 6 · 2016: 11 · 2015: 11 · 2014: 11 · 2013: 11 · 2012: 13
- FWCI
- 4.56
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- American Journal of Physiology-Endocrinology and Metabolism (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion, cc-by)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- Akt, insulin signaling, adipocytes, lipid metabolism, PDE3B, AMPK, acetyl-CoA carboxylase, de novo lipogenesis, lipogenesis, PI3K signaling
- MeSH terms
- Animals, Cells, Cultured, Humans, Insulin, Lipolysis, Male, Models, Biological, Signal Transduction, Rats, Sprague-Dawley, Adipocytes, 3T3-L1 Cells, Protein Kinase Inhibitors, Extracellular Signal-Regulated MAP Kinases, Lipogenesis, Lipid Metabolism, Proto-Oncogene Proteins c-akt, Mice, Rats, Cyclic Nucleotide Phosphodiesterases, Type 3
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
