Epithelial TMPRSS2 impairs glucose homeostasis in obese mice by regulating ghrelin-GLP-1 receptor signaling pathway - PubMed
3 hours ago
- #GLP-1
- #Obesity
- #Metabolism
- Epithelial TMPRSS2 impairs glucose homeostasis in obese mice by regulating the ghrelin-GLP-1 receptor signaling pathway.
- TMPRSS2, co-expressed with PAR2 in intestinal epithelial cells, plays a key role in deregulating anti-diabetic GLP-1 production in obesity.
- TMPRSS2 activates PAR2, promoting postprandial GIP release, unlike other proteases like FXa or matriptase.
- A PAR2 mutant mouse resistant to TMPRSS2 cleavage is protected from GIP upregulation and diet-induced obesity.
- In obesity, TMPRSS2 attenuates ghrelin pathway bioavailability, suppressing GLP-1-mediated glucose homeostasis control.
- Pharmacological inhibition or genetic deletion of TMPRSS2 restores ghrelin signaling-dependent GLP-1 secretion and its anti-diabetic effects.
- TMPRSS2, known for its role in SARS-CoV-2 lung pathology, emerges as an intestinal incretin regulator, linking infection to chronic cardiometabolic diseases.