Epithelial TMPRSS2 impairs glucose homeostasis in obese mice by regulating ghrelin-GLP-1 receptor signaling pathway
Kaur D., Chakrabarty S., Witzler C., Wang H., Wang M., Wolz R.
Animal Study, published in JCI Insight (2026) — summary generated from the PubMed abstract.
Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.
- Level A · Stronger Clinical Evidence
- Level B · Emerging clinical evidence with positive signals
- Level C · Early human research exploring benefits
- Level D · Scientific groundwork from lab and animal studies
- Emerging · Emerging topic under active research
This page is generated from the PubMed record. The Thai description is an automated summary of bibliographic fields and the abstract, not a full translation, and is not medical advice.
- Study type
- Animal Study
- Journal
- JCI Insight (2026)
- Reported sample size
- —
- Source database
- Europe PMC
- PMID
- 41842964
- PMCID
- PMC13167073
- DOI
- 10.1172/jci.insight.203211
Abstract (original English)
Glucagon-like peptide-1 (GLP-1) and glucose-induced insulinotropic polypeptide (GIP) receptor agonists have revolutionized obesity therapy, but causes of obesity-associated dysregulation of endogenous incretin production remain incompletely understood. Here we show that intestinal transmembrane serine protease 2 (TMPRSS2) plays a pivotal role in deregulating anti-diabetic GLP-1 production in obesity. TMPRSS2 is widely coexpressed in intestinal epithelial cells along with its signaling target protease-activated receptor 2 (PAR2). In addition to its role in regulating coagulation protease-mediated adipose tissue inflammation, PAR2 signaling in the gut controls postprandial GIP secretion. TMPRSS2, but not the epithelial cell-expressed proteases FXa or matriptase, activates PAR2 and thereby promotes postprandial GIP release. Accordingly, a PAR2-mutant mouse resistant to TMPRSS2 cleavage is protected from GIP upregulation and diet-induced obesity. In the context of obesity, TMPRSS2 also attenuates bioavailability of the ghrelin pathway and thereby suppresses GLP-1-mediated control of glucose homeostasis. Pharmacological inhibition or genetic deletion of TMPRSS2 restores ghrelin signaling-dependent GLP-1 secretion and GLP-1's anti-diabetic effects on nutritional glucose homeostasis. Thus, epithelial cell-expressed TMPRSS2, which critically contributes to the lung pathology in SARS-Co
What this study does not prove
- • This study does not prove SVF is an approved treatment or a replacement for standard care.
- • This is preclinical work; animal or laboratory results cannot be applied to humans.
Evidence level
Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.
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