Tissue origins of the plasma proteomic response to glucose ingestion in humans.

Authors

Burulça Uluvar, Alice Williamson, Kristoffer J Kolnes, Per Bendix Jeppesen, Anders J Kolnes, Mine Koprulu, Martijn Zoodsma, Carl Beuchel, Yanki Bambal, Mar Reines, Summaira Yasmeen, Carlo Maj, Johannes Schumacher, Stephen O'Rahilly, David A van Heel, Sina Bartfeld, Julia Carrasco-Zanini, Jørgen Jensen, Maik Pietzner, Claudia Langenberg

Published in

Diabetologia. Jul 17, 2026. Epub Jul 17, 2026.

Abstract

Circulating proteins act as important hormonal signals of nutrient intake. We aimed to systematically characterise the time-resolved proteomic response to glucose ingestion in humans, and to assess its robustness following prolonged complete caloric restriction.
We conducted oral glucose tolerance tests (OGTTs) in 11 healthy volunteers before and after 7 days of complete caloric restriction and measured the response of >2900 targets through high-resolution plasma protein profiling.
We identified a signature of 44 proteins that changed significantly following glucose ingestion, which was reproducible after 7 days without food, and was strongly (20-fold) enriched for 'stomach-specific' proteins. We report that annexin A10 (ANXA10) shows the most significant post-glucose change observed, similar to the trajectories of secreted hormones. We present observational human evidence from multiple sources suggesting that ANXA10 is secreted upon sensing an increase in gastric pH, with the stomach as the major contributing tissue. Despite a profound metabolic shift after 7 days of complete caloric restriction, characterised by delayed insulin secretion and postprandial hyperglycaemia, only four proteins showed robust evidence for a differential trajectory during both OGTTs. This included plasma levels of tryptophanyl-tRNA synthetase 1 (WARS), for which we found a genetic association with glucose homeostasis and coronary artery disease.
Our exploratory study identifies the proteomic response to glucose ingestion and demonstrates its reproducibility despite major shifts in glucose homeostasis. We characterise the gastrointestinal origin of these changes, and hypothesise a hitherto under-recognised role for sensing of changes in gastric pH on the plasma proteome.

PMID:
42467085
Bibliographic data and abstract were imported from PubMed on 17 Jul 2026.

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