Lessons from neonatal β-cell epigenomic for diabetes prevention and treatment. (June 2022)

• Record Type: Journal Article
• Authors: Abderrahmani, Amar; Jacovetti, Cécile; Regazzi, Romano
• Is Part Of: Trends in endocrinology and metabolism. Volume 33:Number 6(2022)
• Page Start: 378
• Page End: 389
• Publication Date: 2022-06
• Subjects: β-cell replication -- newborn -- epigenetic -- weaning -- obesity -- diabetes; Endocrinology -- Periodicals; Metabolism -- Periodicals; Metabolism; 616.4
• DOI: 10.1016/j.tem.2022.03.002
• Languages: English
• ISSNs: 1043-2760

Abstract

Abstract : Pancreatic β-cell expansion and functional maturation during the birth-to-weaning period plays an essential role in the adaptation of plasma insulin levels to metabolic needs. These events are driven by epigenetic programs triggered by growth factors, hormones, and nutrients. These mechanisms operating in the neonatal period can be at least in part reactivated in adult life to increase the functional β-cell mass and face conditions of increased insulin demand such as obesity or pregnancy. In this review, we will highlight the importance of studying these signaling pathways and epigenetic programs to understand the causes of different forms of diabetes and to permit the design of novel therapeutic strategies to prevent and treat this metabolic disorder affecting hundreds of millions of people worldwide. Highlights: Expansion of β-cell mass during suckling period relies on epigenetic program connected to specific signaling pathways of humoral factors. Maternal milk, innate immunity, and intestinal microbiota are keys for the control of the epigenetic mechanisms governing cell cycle entry pathways during the lactating period. Nutritional switch during suckling–weaning transition induces a change in the epigenetic pathways leading to the growth arrest and β-cell maturation. Pathways involved in postnatal constitutive and adaptive β-cell replication are reactivated during pregnancy and obesity. In diabetes, activation of epigenetic pathways involved in neonate β-cell proliferation is impaired. Understanding how to manipulate these pathways can be foreseen as a possible therapeutic treatment option to restore the lost β-cell mass in diabetes.