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 journalArticlepeer-review

4 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

ASJC Scopus subject areas

  • General

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