ESPEYB18 10. Type 1 Diabetes Mellitus (1) (14 abstracts)
10.14. Targeted pharmacological therapy restores [beta]-cell function for diabetes remission
Sachs S , Bastidas-Ponce A , Tritschler S , Bakhti M , Böttcher A , Sánchez-Garrido MA , Tarquis-Medina M , Kleinert M , Fischer K , Jall S , Harger A , Bader E , Roscioni S , Ussar S , Feuchtinger A , Yesildag B , Neelakandhan A , Jensen CB , Cornu M , Yang B , Finan B , Di Marchi RD , Tschöp MH , Theis FJ , Hofmann SM , Müller TD & Lickert H
Nature Metabolism. 2020;2(2):192–209. doi: 10.1038/s42255-020-0171-3.
This experimental mouse study examined whether or not dedifferentiated β cells could be reversed or targeted by pharmacological intervention for diabetes remission. They identified evidence for β-cell dedifferentiation and dysfunction which could be reversed by single and combined pharmacological approaches.
Dedifferentiation is a process whereby mature differentiated cells transition back to a less mature state to allow potential for regeneration, but with the loss of some cell functions. Dedifferentiation of insulin-secreting β cells in pancreatic islets has been proposed to be a major mechanism of β-cell dysfunction. In this study, mice with streptozotocin-induced diabetes were used as a model to study β-cell dedifferentiation. Single-cell RNA sequencing (scRNA-seq) of islet cells identified markers and pathways associated with β-cell dedifferentiation and dysfunction.
Administration of insulin triggered insulin receptor pathway activation in β cells and restored cell maturation and function, leading to islet differentiation and diabetes remission. Additionally, β-cell selective delivery of oestrogen combined with Glucagon-like peptide-1 (GLP-1-oestrogen) decreased insulin requirements by 60%, triggered oestrogen-specific activation of the endoplasmic-reticulum-associated protein degradation system, and further increased β-cell survival and even regeneration. The GLP-1-oestrogen combination also protected human β cells against cytokine-induced dysfunction.
This study not only describes mechanisms of β-cell dedifferentiation and regeneration, but also reveals potential pharmacological entry points to target dedifferentiated β cells for diabetes remission and cure.
Volume 18
Article tools
My recent searches
My recently viewed abstracts
Authors
ESPE Yearbook of Paediatric Endocrinology
ISSN 1662-4009 (Online)
© Bioscientifica 2024 |
Privacy policy |
Cookie settings
BiosciAbstracts
Bioscientifica Abstracts is the gateway to a series of products that provide a permanent, citable record of abstracts for biomedical and life science conferences.
Find out more