Abstract

Pregnancy is a period of extensive metabolic rewiring. Insulin secreting β-cells respond to the metabolic challenges of pregnancy by increasing their mass and size and by altering secretory patterns to maintain glucose homeostasis. If glucose metabolism is not tightly controlled, gestational diabetes may develop. Most studies on β-cell adaptation during pregnancy are derived from rodent models, making translation to the vastly different human gestational setting challenging. In this work, we performed an extensive characterization of pancreatic adaptations throughout porcine pregnancy. Pigs have a long gestational period (114 days) and share a similar size and metabolism to humans, making them an ideal model to bridge the knowledge gap between rodents and humans. By analyzing pancreatic samples from early and late gestational ages, we captured the full trajectory of endocrine remodeling. We observed pregnancy-driven remodeling of endocrine cell types, marked by preferential expansion of pancreatic polypeptide-secreting cells. Proteomic characterization of the pancreas from early and late gestation showed a downregulation of SLC20A2 and ZCCHC7, identifying new protein targets involved in physiological endocrine cell adaptation. Overall, our comprehensive characterization of pancreatic adaptations in the pig model helps bridge the translational gap between rodents and humans and highlights previously unrecognized proteins with therapeutic potential for gestational diabetes.