ArticleJCI insight2026
Epithelial TMPRSS2 impairs glucose homeostasis in obese mice by regulating ghrelin-GLP-1 receptor signaling pathway.
Article in JCI insight, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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-CoV-2 infection, emerges as an intestinal incretin regulator and a potential link between infection and chronic cardiometabolic diseases.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.