Increased TGF β /Activin-Smad2 signaling is associated with pancreatic β -cell dysfunction and glucose intolerance in gestational diabetes mellitus

• DOI: 10.1101/2025.02.16.638404
• Publication Date: 2025-02-21T04:10:18Z
• Authors: Talía Boronat-Belda; Hilda Ferrero; Sergi Soriano; Elena Ribes-García; Rubén Betoret-Gus...; Daniel Martínez-B...; Mónica Serrano-Selva; Juan Martínez-Pinna; Ángel Nadal; Iván Quesada; Paloma Alonso- Ma...

Background: Gestational diabetes mellitus (GDM) is the most common metabolic disease during pregnancy and increases prevalence of type 2 in both mothers offspring. GDM management provides a window opportunity to prevent lower global burden across life. Molecular mechanisms underlying are poorly defined. In this study, we explore potential involvement transforming growth factor beta (TGF-β) signaling as pathway has been reported affect pancreatic β-cell development, proliferation identity. Methods: We developed animal model. Serum circulating levels TGFβ family ligands were measured mice human GDM. Pancreatic was investigated at level gene protein expression. Results: Our model recapitulates main pathophysiological features including glucose intolerance, decreased insulin sensitivity malfunction. Islets from showed impaired secretion content, altered ion channel activity, replication rate. This accompanied by increased Smad2 activation. Elevated serum activin-A inhibin found GDM, suggesting their role upstream transducers Pharmacological inhibition TGFβ/Activin-Smad2 mouse islets resulted improved function regeneration capacity β-cells. Conclusions: data disclose that disruption plays critical pathogenesis contributing abnormal homeostasis inadequate secretion. Attenuation could represent putative therapeutic target for