Nepetin Acts as a Multi‐Targeting Inhibitor of Protein Tyrosine Phosphatases Relevant to Insulin Resistance

• Published in: Chemistry & biodiversity Vol. 19; no. 1; pp. e202100600 - n/a
• Main Authors: Yoon, Sun‐Young, Ahn, Dohee, Kim, Jae kwan, Seo, Seung‐Oh, Chung, Sang J.
• Format: Journal Article
• Language: English
• Published: Switzerland Wiley Subscription Services, Inc 01.01.2022
• Subjects: 3T3-L1 Cells; Adipocytes; AMP-Activated Protein Kinases - metabolism; Animals; Autoimmune diseases; Biocatalysis; Catalytic activity; Chemical compounds; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - pathology; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - metabolism; Enzyme Inhibitors - therapeutic use; Flavones - chemistry; Flavones - metabolism; Flavones - therapeutic use; Glucose - metabolism; glucose uptake; Humans; Inhibitors; Insulin; Insulin Resistance; Mice; Modulators; nepetin; Neurological diseases; Neuromodulation; Pharmacology; Phosphatase; Phosphorylation - drug effects; Protein Tyrosine Phosphatase, Non-Receptor Type 1 - antagonists & inhibitors; Protein Tyrosine Phosphatase, Non-Receptor Type 1 - metabolism; Protein Tyrosine Phosphatase, Non-Receptor Type 11 - antagonists & inhibitors; Protein Tyrosine Phosphatase, Non-Receptor Type 11 - metabolism; Protein Tyrosine Phosphatase, Non-Receptor Type 2 - antagonists & inhibitors; Protein Tyrosine Phosphatase, Non-Receptor Type 2 - metabolism; Protein tyrosine phosphatases (PTPs); Protein Tyrosine Phosphatases - antagonists & inhibitors; Protein Tyrosine Phosphatases - metabolism; Proteins; PTPN1; PTPN11; PTPN2; PTPN2 protein; Signal transduction; Therapeutic targets; type-2 diabetes; Tyrosine; PTPN1; glucose uptake; type-2 diabetes; catalytic activity; PTPN11; Protein tyrosine phosphatases (PTPs); nepetin; PTPN2
• ISSN: 1612-1872; 1612-1880
• DOI: 10.1002/cbdv.202100600

Protein tyrosine phosphatases (PTPs) are essential modulators of signal transduction pathways and has been implicated in many human diseases such as cancer, diabetes, obesity, autoimmune disorders, and neurological diseases, indicating that PTPs are next‐generation drug targets. Since PTPN1, PTPN2, and PTPN11 have been reported to be negative regulators of insulin action, the identification of PTP inhibitors may be an effective strategy to develop therapeutic agents for the treatment of type 2 diabetes. In this study, we observed for the first time that nepetin inhibits the catalytic activity of PTPN1, PTPN2, and PTPN11 in vitro, indicating that nepetin acts as a multi‐targeting inhibitor of PTPN1, PTPN2, and PTPN11. Furthermore, treatment of mature 3T3‐L1 adipocytes with 20 μM nepetin stimulates glucose uptake through AMPK activation. Taken together, our findings provide evidence that nepetin, a multi‐targeting inhibitor of PTPN1, PTPN2, and PTPN11, could be a promising therapeutic candidate for the treatment of type 2 diabetes.