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Pancreatic islet β-cell subtypes are derived from biochemically-distinct and nutritionally-regulated islet progenitors
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Pancreatic islet β-cell subtypes are derived from biochemically-distinct and nutritionally-regulated islet progenitors
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Journal Article
Pancreatic islet β-cell subtypes are derived from biochemically-distinct and nutritionally-regulated islet progenitors
2025
Overview
Endocrine islet β cells comprise heterogenous subtypes with different gene expression and function levels. Here we study when/how this heterogeneity is induced and how long each subtype maintains its characteristic properties. We show that islet progenitors with distinct gene expression and DNA methylation patterns produce β-cell subtypes of different secretory function, proliferation rate, and viability in male and female mice. These subtypes have differential gene expression that regulates insulin vesicle production or stimulation-secretion coupling and differential DNA methylation in the putative enhancers of these genes. Maternal obesity, a major diabetes risk factor, reduces the proportion of the β-cell subtype with higher levels of glucose responsiveness. The gene signature that defines mouse β-cell subtypes can reliably divide human cells into two sub-populations, with the one having higher predicted glucose responsiveness reduced in diabetic donors. These results suggest that β-cell subtypes can be derived from islet progenitor subsets modulated by maternal nutrition.
Brown et al. show that mouse islet progenitors with different transcriptomes produce distinct β-cell subtypes and maternal diet alter the subtype proportions. Similar β-cell subsets exist in humans, with a subset enriched in genes related to β cell function reduced in diabetes.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
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/ Animals
/ Cells
/ Diabetes
/ DNA
/ Female
/ Females
/ Genes
/ Glucose
/ Humanities and Social Sciences
/ Humans
/ Insulin
/ Insulin-Secreting Cells - cytology
/ Insulin-Secreting Cells - metabolism
/ Islets of Langerhans - cytology
/ Islets of Langerhans - metabolism
/ Male
/ Males
/ Mice
/ Science
