Melnik, Bodo C. and Weiskirchen, Ralf and Weiskirchen, Sabine and Stremmel, Wolfgang and John, Swen M. and Leitzmann, Claus and Schmitz, Gerd (2025) Diabetes-preventive molecular mechanisms of breast versus formula feeding: new insights into the impact of milk on stem cell Wnt signaling. FRONTIERS IN NUTRITION, 12: 1652297. ISSN 2296-861X
Full text not available from this repository. (Request a copy)Abstract
Human milk serves as a transmitter for epigenetic programming involved in postnatal tissue development and organ maturation of the infant. In contrast to formula feeding (FF), prolonged breastfeeding (BF) has been associated with diabetes-preventive effects. Polymorphisms of the transcription factor 7-like 2 (TCF7L2), the key downstream effector of Wingless (Wnt) signaling, increase the risk of diabetes mellitus. Wnt signaling is crucial for beta-cell development and proliferation. However, there is limited information regarding Wnt/beta-catenin/TCF7L2-dependent effects of BF versus FF on postnatal beta-cell progenitor cell development, beta-cell proliferation and beta-cell mass expansion. The objective of our literature review is to collect and analyze data to provide translational evidence that different components of human milk promote Wnt signaling. We will specifically focus on the variations in Wnt signaling in enteroendocrine L-cells and pancreatic beta-cells in response to either FF or BF. FF-induced overstimulation of mTORC1 may suppress Wnt gene expression through S6K1-mediated histone H3K27 trimethylation (H3K27me3). Moreover, the absence of milk exosomal miRNAs in formula that target mRNAs of crucial Wnt inhibitors, as well as reduced levels of eicosapentaenoic acid and glutamine in formula, may further hinder appropriate Wnt signaling, negatively impacting intestinal stem cells, enteroendocrine L-cells and potentially beta-cell progenitor cells. Overall, the evidence presented supports the conclusion that FF has a detrimental impact on the Wnt/beta-catenin/TCF7L2-regulated enteroendocrine-islet axis, disrupting proper beta-cell maturation and proliferation. We propose that human milk, compared to formula, offers optimized conditions for physiological Wnt signaling promoting adequate neonatal beta-cell mass expansion, which could explain the early diabetes-preventive effects of prolonged BF.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GLUCAGON-LIKE PEPTIDE-1; WNT/BETA-CATENIN PATHWAY; PANCREATIC BETA-CELLS; POLYUNSATURATED FATTY-ACIDS; IN-VITRO EXPANSION; PRETERM HUMAN-MILK; FREE AMINO-ACIDS; SMALL-INTESTINE; PROTEIN-INTAKE; ALPHA-CELLS; breastfeeding; diabetes mellitus; milk exosome; microRNA; formula feeding; wingless signaling; beta-cell; diabetes prevention |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 07 May 2026 08:15 |
| Last Modified: | 07 May 2026 08:15 |
| URI: | https://pred.uni-regensburg.de/id/eprint/67348 |
Actions (login required)
 |
View Item |
