Importance of Both Imprinted Genes and Functional Heterogeneity in Pancreatic Beta Cells: Is There a Link?
Year: 2021
Type: review
Abstract: Diabetes mellitus now affects more than 400 million individuals worldwide, with significant impacts on the lives of those affected and associated socio-economic costs. Although defects in insulin secretion underlie all forms of the disease, the molecular mechanisms which drive them are still poorly understood. Subsets of specialised beta cells have, in recent years, been suggested to play critical roles in "pacing" overall islet activity. The molecular nature of these cells, the means through which their identity is established and the changes which may contribute to their functional demise and "loss of influence" in both type 1 and type 2 diabetes are largely unknown. Genomic imprinting involves the selective silencing of one of the two parental alleles through DNA methylation and modified imprinted gene expression is involved in a number of diseases. Loss of expression, or loss of imprinting, can be shown in mouse models to lead to defects in beta cell function and abnormal insulin secretion. In the present review we survey the evidence that altered expression of imprinted genes contribute to loss of beta cell function, the importance of beta cell heterogeneity in normal and disease states, and hypothesise whether there is a direct link between the two.
DOI: 10.3390/ijms22031000
Institution: Imperial College London
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,160
Awards: Investigating the role of immature beta cells in insulin release from the intact islet, G130968091, G1335979935, G1635243398, Genetic and nutritional control of pancreatic beta cell identity., G1937207371, Roles of GWA genes in controlling pancreatic beta cell function and mass., G2040450235, Control of glucagon secretion by AMPK and related kinases., G2961113885, G3346581055, Assessing risk and progression of prediabetes and type 2 diabetes to enable disease modification - Sofia ref.: 115881, G4426574518, G4781795914, All-optical deconstruction of the islet wiring patterns underlying insulin secretion in health and disease, Targeting etiologic molecular mechanisms to treat human diabetes, G5673545276, The impact of long non-coding RNA at the Pax6 locus on beta cell identity and function, G6133425169, Defining the molecular and physiological mechanisms of pancreatic islet dysfunction which lead to type 2 diabetes, G6693145033, Coordination and Advancement of sub-Saharan Africa-EU Science & Technology Cooperation Network, Understanding pancreatic beta cell connectivity, G7328074751, G7571465722, G8635620823, G8897119323, G9000168923
OpenAlex ID: W3125717033