Inhibition of C1-Ten PTPase activity reduces insulin resistance through IRS-1 and AMPK pathways

Heeyoon Jeong, Ara Koh, Jiyoun Lee, Dohyun Park, Jung Ok Lee, Mi Nam Lee, Kyung Jin Jo, Huynh Nguyen Khanh Tran, Eui Kim, Byung Sun Min, Hyeon Soo Kim, Per Olof Berggren, Sung Ho Ryu

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Insulin resistance causes type 2 diabetes; therefore, increasing insulin sensitivity is a therapeutic approach against type 2 diabetes. Activating AMP-activated protein kinase (AMPK) is an effective approach for treating diabetes, and reduced insulin receptor substrate-1 (IRS-1) protein levels have been suggested as a molecular mechanism causing insulin resistance. Thus, dual targeting of AMPK and IRS-1 might provide an ideal way to treat diabetes. We found that 15,16-dihydrotanshinone I (DHTS), as a C1-Ten protein tyrosine phosphatase inhibitor, increased IRS-1 stability, improved glucose tolerance and reduced muscle atrophy. Identification of DHTS as a C1-Ten inhibitor revealed a new function of C1-Ten in AMPK inhibition, possibly through regulation of IRS-1. These findings suggest that C1-Ten inhibition by DHTS could provide a novel therapeutic strategy for insulin resistance-associated metabolic syndrome through dual targeting of IRS-1 and AMPK.

Original languageEnglish
Article number17777
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - 2017 Dec 1

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Insulin Receptor Substrate Proteins
AMP-Activated Protein Kinases
Protein Tyrosine Phosphatases
Insulin Resistance
Type 2 Diabetes Mellitus
Muscular Atrophy
Glucose
Therapeutics
15,16-dihydrotanshinone I

ASJC Scopus subject areas

  • General

Cite this

Jeong, H., Koh, A., Lee, J., Park, D., Lee, J. O., Lee, M. N., ... Ryu, S. H. (2017). Inhibition of C1-Ten PTPase activity reduces insulin resistance through IRS-1 and AMPK pathways. Scientific Reports, 7(1), [17777]. https://doi.org/10.1038/s41598-017-18081-8

Inhibition of C1-Ten PTPase activity reduces insulin resistance through IRS-1 and AMPK pathways. / Jeong, Heeyoon; Koh, Ara; Lee, Jiyoun; Park, Dohyun; Lee, Jung Ok; Lee, Mi Nam; Jo, Kyung Jin; Tran, Huynh Nguyen Khanh; Kim, Eui; Min, Byung Sun; Kim, Hyeon Soo; Berggren, Per Olof; Ryu, Sung Ho.

In: Scientific Reports, Vol. 7, No. 1, 17777, 01.12.2017.

Research output: Contribution to journalArticle

Jeong, H, Koh, A, Lee, J, Park, D, Lee, JO, Lee, MN, Jo, KJ, Tran, HNK, Kim, E, Min, BS, Kim, HS, Berggren, PO & Ryu, SH 2017, 'Inhibition of C1-Ten PTPase activity reduces insulin resistance through IRS-1 and AMPK pathways', Scientific Reports, vol. 7, no. 1, 17777. https://doi.org/10.1038/s41598-017-18081-8
Jeong, Heeyoon ; Koh, Ara ; Lee, Jiyoun ; Park, Dohyun ; Lee, Jung Ok ; Lee, Mi Nam ; Jo, Kyung Jin ; Tran, Huynh Nguyen Khanh ; Kim, Eui ; Min, Byung Sun ; Kim, Hyeon Soo ; Berggren, Per Olof ; Ryu, Sung Ho. / Inhibition of C1-Ten PTPase activity reduces insulin resistance through IRS-1 and AMPK pathways. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
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