Insulin stimulation of glycogen synthesis and glycogen synthase activity is blocked by wortmannin and rapamycin in 3T3-L1 adipocytes: evidence for the involvement of phosphoinositide 3-kinase and p70 ribosomal protein-S6 kinase

Shepherd, P R; Navé, B T; Siddle, K

doi:10.1042/bj3050025

Cited by 277Metabolism, Diabetes, and CancerPI3K/AKT/mTOR signaling in cancerProtein Kinase Regulation and GTPase Signaling

Insulin stimulation of glycogen synthesis and glycogen synthase activity is blocked by wortmannin and rapamycin in 3T3-L1 adipocytes: evidence for the involvement of phosphoinositide 3-kinase and p70 ribosomal protein-S6 kinase

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Shepherd, P R, Navé, B T, Siddle, K·1995·Biochemical Journal

DOI 10.1042/bj3050025PMC PMC1136424

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Abstract

We have investigated the involvement of phosphoinositide (PI) 3-kinase and p70 ribosomal protein-S6 kinase (p70s6k) in mediating insulin stimulation of glycogen synthesis in 3T3-L1 adipocytes using specific inhibitors. Wortmannin inhibited PI 3-kinase activity (IC50 approximately 10 nM), inhibition being complete at 100 nm. Wortmannin (100 nM) completely blocked the ability of insulin to activate glycogen synthase in 3T3-L1 adipocytes and the ability of insulin to stimulate glucose incorporation into glycogen in 3T3-L1 fibroblasts. Rapamycin, which blocks insulin-stimulated activation of p70s6k, decreased insulin activation of glycogen synthase in a dose-dependent manner (IC50 approximately 0.8 ng/ml), with a maximum approx. 75% inhibition of insulin's stimulatory effect. Rapamycin inhibited insulin-stimulated glucose incorporation into glycogen to a similar extent and with similar dose-dependency, while having no effect on insulin-stimulated glucose transport. We conclude that PI 3-kinase and p70s6k are involved in the signalling pathways by which insulin stimulates glycogen synthase in 3T3-L1 adipocytes.

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Inhibitors of PI3K inhibit glycogen synthase activity and abolish glycogen synthesis.
“Studies [138, 150] have demonstrated convincingly that inhibitors of PI3K inhibit glycogen synthase activity and abolish glycogen synthesis.”
From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [150]
Glycogen synthase is the key insulin-regulated enzyme controlling the rate of muscle glycogen synthesis.
“Glycogen synthase is the key insulin-regulated enzyme that controls the rate of muscle glycogen synthesis [148, 150, 200, 212–214].”
From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [150]
Glycogen synthase exists in active (dephosphorylated) and inactive (phosphorylated) forms.
“Glycogen synthase exists in an active (dephosphorylated) and an inactive (phosphorylated) form [148–150].”
From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [150]

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Authors: Shepherd, P. R., Navé, B. T., & Siddle, K.
Affiliations: University of Cambridge (GB)
ORCID: Shepherd, P R
Venue: Biochemical Journal
Publisher: Portland Press Ltd.
Published: 1995-01-01
Volume: 305
Issue: 1
Pages: 25-28
ISSN: 0264-6021 (ISSN-L)
1470-8728
DOI: 10.1042/bj3050025
PMC: PMC1136424
OpenAlex: W1947575656
Cited by: 277
References: 44
Citations by year: 2025: 1 · 2024: 1 · 2022: 2 · 2021: 2 · 2020: 1 · 2019: 3 · 2018: 8 · 2017: 4 · 2016: 2 · 2015: 11 · 2014: 2 · 2013: 4 · 2012: 4
FWCI: 10.28
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Biochemical Journal (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Wellcome Trust
Novo Nordisk
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
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Keywords: insulin signaling, glycogen synthesis, glycogen synthase, phosphatidylinositol 3-kinase, wortmannin, rapamycin, 3T3-L1 adipocytes, insulin-stimulated glucose transport
MeSH terms: Wortmannin, Androstadienes, Animals, Enzyme Activation, Enzyme Inhibitors, Glycogen, Glycogen Synthase, Insulin, Insulin Antagonists, Kinetics, Polyenes, Stimulation, Chemical, 3T3 Cells, Protein Serine-Threonine Kinases, Adipocytes, Phosphotransferases (Alcohol Group Acceptor), Phosphatidylinositol 3-Kinases, Ribosomal Protein S6 Kinases, Sirolimus, Mice

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Insulin stimulation of glycogen synthesis and glycogen synthase activity is blocked by wortmannin and rapamycin in 3T3-L1 adipocytes: evidence for the involvement of phosphoinositide 3-kinase and p70 ribosomal protein-S6 kinase

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