Insulin signalling downstream of protein kinase B is potentiated by 5′AMP-activated protein kinase in rat hearts in vivo

Longnus, S. L.; Ségalen, C.; Giudicelli, J.; Sajan, M. P.; Farese, R. V.; Van Obberghen, E.

doi:10.1007/s00125-005-0016-3

Cited by 58Metabolism, Diabetes, and CancerPI3K/AKT/mTOR signaling in cancerNatural Antidiabetic Agents Studies

Insulin signalling downstream of protein kinase B is potentiated by 5′AMP-activated protein kinase in rat hearts in vivo

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Longnus, S. L., Ségalen, C., Giudicelli, J., Sajan, M. P., Farese, R. V., Van Obberghen, E.·2005·Diabetologia

DOI 10.1007/s00125-005-0016-3

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Abstract

Aims/hypothesis 5'AMP-activated protein kinase (AMPK) and insulin stimulate glucose transport in heart and muscle. AMPK acts in an additive manner with insulin to increase glucose uptake, thereby suggesting that AMPK activation may be a useful strategy for ameliorating glucose uptake, especially in cases of insulin resistance. In order to characterise interactions between the insulin- and AMPK-signalling pathways, we investigated the effects of AMPK activation on insulin signalling in the rat heart in vivo.Methods Male rats (350-400 g) were injected with 1 g/kg 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR) or 250 mg/kg metformin in order to activate AMPK. Rats were administered insulin 30 min later and after another 30 min their hearts were removed. The activities and phosphorylation levels of components of the insulin-signalling pathway were subsequently analysed in individual rat hearts.Results AICAR and metformin administration activated AMPK and enhanced insulin signalling downstream of protein kinase B in rat hearts in vivo. Insulin-induced phosphorylation of glycogen synthase kinase 3 (GSK3) beta, p70 S6 kinase (p70S6K)(Thr389) and IRS1(Ser636/639) were significantly increased following AMPK activation. To the best of our knowledge, this is the first report of heightened insulin responses of GSK3beta and p70S6K following AMPK activation. In addition, we found that AMPK inhibits insulin stimulation of IRS1-associated phosphatidylinositol 3-kinase activity, and that AMPK activates atypical protein kinase C and extracellular signal-regulated kinase in the heart.Conclusions/interpretations Our data are indicative of differential effects of AMPK on the activation of components in the cardiac insulin-signalling pathway. These intriguing observations are critical for characterisation of the crosstalk between AMPK and insulin signalling.

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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 [23]

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Authors: Longnus, S. L., Ségalen, C., Giudicelli, J., Sajan, M. P., Farese, R. V., & Van Obberghen, E.
Affiliations: Inserm (FR)
University of South Florida (US)
ORCID: Longnus, S. L.
Farese, R. V.
Venue: Diabetologia
Publisher: Springer Science and Business Media LLC
Published: 2005-11-11
Volume: 48
Issue: 12
Pages: 2591-2601
ISSN: 0012-186X (ISSN-L)
1432-0428
DOI: 10.1007/s00125-005-0016-3
OpenAlex: W1986364902
Cited by: 58
References: 83
Citations by year: 2026: 1 · 2024: 1 · 2023: 1 · 2021: 1 · 2020: 2 · 2019: 1 · 2018: 2 · 2017: 2 · 2016: 4 · 2015: 1 · 2014: 4 · 2013: 4 · 2012: 7
FWCI: 1.99
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.springer.com/tdm (tdm)
Locations: Diabetologia (publishedVersion)
PubMed (publishedVersion)
Funders: Institut National de la Santé et de la Recherche Médicale
National Institutes of Health
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK065969, R01-DK065969-01A1)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Natural Antidiabetic Agents Studies
Keywords: AMPK, insulin signaling, Akt, glycogen synthase kinase-3β, p70 S6 kinase, IRS-1, phosphatidylinositol 3-kinase, atypical protein kinase C, extracellular signal-regulated kinase, glucose uptake, AICAR, metformin, insulin resistance
MeSH terms: Glycogen Synthase Kinase 3 beta, Aminoimidazole Carboxamide, Animals, Blood Glucose, Enzyme Activation, Heart, Insulin, Male, Metformin, Multienzyme Complexes, Myocardium, Phosphoproteins, Phosphorylation, Protein Kinase C, Ribonucleotides, Signal Transduction, Rats, Sprague-Dawley, Protein Serine-Threonine Kinases, Phosphatidylinositol 3-Kinases, Glycogen Synthase Kinase 3, Ribosomal Protein S6 Kinases, 70-kDa, Mitogen-Activated Protein Kinase 3, Proto-Oncogene Proteins c-akt, Rats, AMP-Activated Protein Kinases, Insulin Receptor Substrate Proteins

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Insulin signalling downstream of protein kinase B is potentiated by 5′AMP-activated protein kinase in rat hearts in vivo

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