PAR2 promotes impaired glucose uptake and insulin resistance in NAFLD through GLUT2 and Akt interference

Autor:	Andrew M. Shearer, Yanling Wang, Elizabeth K. Fletcher, Rajashree Rana, Emily S. Michael, Nga Nguyen, Manal F. Abdelmalek, Lidija Covic, Athan Kuliopulos
Rok vydání:	2022
Předmět:	Mice Knockout Mice Glucose Hepatology Liver Non-alcoholic Fatty Liver Disease Animals Receptor PAR-2 Insulin Insulin Resistance Proto-Oncogene Proteins c-akt Diabetes Mellitus Experimental
Zdroj:	Hepatology (Baltimore, Md.). 76(6)
ISSN:	1527-3350
Popis:	Insulin resistance and poor glycemic control are key drivers of the development of NAFLD and have recently been shown to be associated with fibrosis progression in NASH. However, the underlying mechanisms involving dysfunctional glucose metabolism and relationship with NAFLD/NASH progression remain poorly understood. We set out to determine whether protease-activated receptor 2 (PAR2), a sensor of extracellular inflammatory and coagulation proteases, links NAFLD and NASH with liver glucose metabolism.Here, we demonstrate that hepatic expression of PAR2 increases in patients and mice with diabetes and NAFLD/NASH. Mechanistic studies using whole-body and liver-specific PAR2-knockout mice reveal that hepatic PAR2 plays an unexpected role in suppressing glucose internalization, glycogen storage, and insulin signaling through a bifurcating GThis work provides evidence that PAR2 is a major regulator of liver glucose homeostasis and a potential target for the treatment of diabetes and NASH.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b288205deeff312daf3bc0e4098ed245 https://pubmed.ncbi.nlm.nih.gov/35603482 Zobrazit plný text záznamu Plný text