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Publication : A beta cell subset with enhanced insulin secretion and glucose metabolism is reduced in type 2 diabetes.

First Author  Rubio-Navarro A Year  2023
Journal  Nat Cell Biol Volume  25
Issue  4 Pages  565-578
PubMed ID  36928765 Mgi Jnum  J:361117
Mgi Id  MGI:7520959 Doi  10.1038/s41556-023-01103-1
Citation  Rubio-Navarro A, et al. (2023) A beta cell subset with enhanced insulin secretion and glucose metabolism is reduced in type 2 diabetes. Nat Cell Biol 25(4):565-578
abstractText  The pancreatic islets are composed of discrete hormone-producing cells that orchestrate systemic glucose homeostasis. Here we identify subsets of beta cells using a single-cell transcriptomic approach. One subset of beta cells marked by high CD63 expression is enriched for the expression of mitochondrial metabolism genes and exhibits higher mitochondrial respiration compared with CD63(lo) beta cells. Human and murine pseudo-islets derived from CD63(hi) beta cells demonstrate enhanced glucose-stimulated insulin secretion compared with pseudo-islets from CD63(lo) beta cells. We show that CD63(hi) beta cells are diminished in mouse models of and in humans with type 2 diabetes. Finally, transplantation of pseudo-islets generated from CD63(hi) but not CD63(lo) beta cells into diabetic mice restores glucose homeostasis. These findings suggest that loss of a specific subset of beta cells may lead to diabetes. Strategies to reconstitute or maintain CD63(hi) beta cells may represent a potential anti-diabetic therapy.
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