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Early growth response‐1 negative feedback regulates skeletal muscle postprandial insulin sensitivity via activating Ptp 1b transcription
Author(s) -
Wu Jing,
Tao WeiWei,
Chong DanYang,
Lai ShanShan,
Wang Chuang,
Liu Qi,
Zhang TongYu,
Xue Bin,
Li ChaoJun
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201701340r
Subject(s) - postprandial , insulin sensitivity , skeletal muscle , endocrinology , medicine , negative feedback , transcription factor , transcription (linguistics) , chemistry , insulin , microbiology and biotechnology , biology , insulin resistance , gene , biochemistry , physics , linguistics , philosophy , quantum mechanics , voltage
Postprandial insulin desensitization plays a critical role in maintaining whole‐body glucose homeostasis by avoiding the excessive absorption of blood glucose; however, the detailed mechanisms that underlie how the major player, skeletal muscle, desensitizes insulin action remain to be elucidated. Herein, we report that early growth response gene‐1 (Egr‐1 ) is activated by insulin in skeletal muscle and provides feedback inhibition that regulates insulin sensitivity after a meal. The inhibition of the transcriptional activity of Egr‐1 enhanced the phosphorylation of the insulin receptor (InsR) and Akt, thus increasing glucose uptake in L6 myotubes after insulin stimulation, whereas overexpression of Egr‐1 decreased insulin sensitivity. Furthermore, deletion of Egr‐1 in the skeletal muscle improved systemic insulin sensitivity and glucose tolerance, which resulted in lower blood glucose levels after refeeding. Mechanistic analysis demonstrated that EGR‐1 inhibited InsR phosphorylation and glucose uptake in skeletal muscle by binding to the proximal promoter region of protein tyrosine phosphatase‐1B (PTP1B) and directly activating transcription. PTP1B knockdown largely restored insulin sensitivity and enhanced glucose uptake, even under conditions of EGR‐1 overexpression. Our results indicate that EGR‐1/PTP1B signaling negatively regulates postprandial insulin sensitivity and suggest a potential therapeutic target for the prevention and treatment of excessive glucose absorption.—Wu, J., Tao, W.‐W., Chong, D.‐Y., Lai, S.‐S., Wang, C., Liu, Q., Zhang, T.‐Y., Xue, B., Li, C.‐J. Early growth response‐1 negative feedback regulates skeletal muscle postprandial insulin sensitivity via activating Ptp1b transcription. FASEB J . 32, 4370–4379 (2018). www.fasebj.org