151. Inhibition of C1-Ten PTPase activity reduces insulin resistance through IRS-1 and AMPK pathways
- Author
-
Ara Koh, Sung Ho Ryu, Dohyun Park, Jiyoun Lee, Hyeon Soo Kim, Huynh Nguyen Khanh Tran, Mi Nam Lee, Heeyoon Jeong, Eui Kim, Kyung Jin Jo, Jung Ok Lee, Per Olof Berggren, and Byung Sun Min
- Subjects
0301 basic medicine ,Male ,medicine.medical_treatment ,lcsh:Medicine ,Type 2 diabetes ,Pharmacology ,AMP-Activated Protein Kinases ,Article ,Cell Line ,03 medical and health sciences ,Mice ,Insulin resistance ,Diabetes mellitus ,medicine ,Animals ,Humans ,Hypoglycemic Agents ,Insulin ,lcsh:Science ,Protein kinase A ,Furans ,Muscle, Skeletal ,Metabolic Syndrome ,Multidisciplinary ,030102 biochemistry & molecular biology ,biology ,Chemistry ,lcsh:R ,Quinones ,AMPK ,Glucose Tolerance Test ,Phenanthrenes ,medicine.disease ,Enzyme Activation ,Mice, Inbred C57BL ,Insulin receptor ,Muscular Atrophy ,030104 developmental biology ,Glucose ,biology.protein ,Insulin Receptor Substrate Proteins ,lcsh:Q ,Metabolic syndrome ,Insulin Resistance ,Protein Tyrosine Phosphatases ,Signal Transduction - 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.
- Published
- 2017