Dataset Information
Increased TGF-β/Activin-Smad2 signaling is associated with pancreatic β-cell dysfunction and glucose intolerance in gestational diabetes mellitus.
Ontology highlight
ABSTRACT: Background
Gestational diabetes mellitus (GDM) is the most common metabolic disease during pregnancy and increases the prevalence of type 2 diabetes in both mothers and children. GDM management provides an opportunity to prevent and lower the global burden of diabetes across life. Molecular mechanisms underlying GDM are not completely understood. In this study, we explore the role of transforming growth factor beta (TGF-β) signaling in GDM, as this pathway reportedly affects pancreatic β-cell development, function, and proliferation.Methods
We developed a GDM animal model. Serum circulating levels of TGF-β family ligands were measured in mice and human GDM. Pancreatic TGF-β signaling was investigated via gene and protein expression.Results
Our GDM animal model recapitulates the main pathophysiological features of human GDM, including glucose intolerance, decreased insulin sensitivity and pancreatic β-cell malfunction. Islets from GDM mice showed impaired insulin secretion and content, altered ion channel activity, and decreased β-cell replication rate. This was accompanied by increased Smad2 signaling activation. Elevated serum activin-A and inhibin levels were found in mice and human GDM, suggesting their role as upstream signaling transducers of pancreatic Smad2 activation. Pharmacological inhibition of TGF-β/Activin-Smad2 signaling in mouse pancreatic islets resulted in improved pancreatic β-cell function and regeneration capacity.Conclusions
Our data suggest that disruption of the pancreatic Smad2 pathway plays a critical role in the pathogenesis of GDM, contributing to abnormal glucose homeostasis and inadequate insulin secretion. Attenuation of this signaling pathway may represent a putative therapeutic target for GDM.
SUBMITTER: Boronat-Belda T
PROVIDER: S-EPMC12902259 | biostudies-literature | 2026 Jan
REPOSITORIES: biostudies-literature
Publications
Increased TGF-β/Activin-Smad2 signaling is associated with pancreatic β-cell dysfunction and glucose intolerance in gestational diabetes mellitus.
Molecular metabolism 20251018
<h4>Background</h4>Gestational diabetes mellitus (GDM) is the most common metabolic disease during pregnancy and increases the prevalence of type 2 diabetes in both mothers and children. GDM management provides an opportunity to prevent and lower the global burden of diabetes across life. Molecular mechanisms underlying GDM are not completely understood. In this study, we explore the role of transforming growth factor beta (TGF-β) signaling in GDM, as this pathway reportedly affects pancreatic β ...[more]