Title | A beta cell subset with enhanced insulin secretion and glucose metabolism is reduced in type 2 diabetes. |
Publication Type | Journal Article |
Year of Publication | 2023 |
Authors | Rubio-Navarro A, Gómez-Banoy N, Stoll L, Dündar F, Mawla AM, Ma L, Cortada E, Zumbo P, Li A, Reiterer M, Montoya-Oviedo N, Homan EA, Imai N, Gilani A, Liu C, Naji A, Yang B, Chong AChi Nok, Cohen DE, Chen S, Cao J, Pitt GS, Huising MO, Betel D, Lo JC |
Journal | Nat Cell Biol |
Volume | 25 |
Issue | 4 |
Pagination | 565-578 |
Date Published | 2023 Apr |
ISSN | 1476-4679 |
Keywords | Animals, Diabetes Mellitus, Experimental, Diabetes Mellitus, Type 2, Glucose, Humans, Insulin, Insulin Secretion, Insulin-Secreting Cells, Mice |
Abstract | <p>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 beta cells. Human and murine pseudo-islets derived from CD63 beta cells demonstrate enhanced glucose-stimulated insulin secretion compared with pseudo-islets from CD63 beta cells. We show that CD63 beta cells are diminished in mouse models of and in humans with type 2 diabetes. Finally, transplantation of pseudo-islets generated from CD63 but not CD63 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 beta cells may represent a potential anti-diabetic therapy.</p> |
DOI | 10.1038/s41556-023-01103-1 |
Alternate Journal | Nat Cell Biol |
PubMed ID | 36928765 |
PubMed Central ID | PMC10449536 |
Grant List | R01 DK121140 / DK / NIDDK NIH HHS / United States R01 DK103046 / DK / NIDDK NIH HHS / United States U24 DK098085 / DK / NIDDK NIH HHS / United States R37 DK048873 / DK / NIDDK NIH HHS / United States R01 DK121844 / DK / NIDDK NIH HHS / United States P30 DK020593 / DK / NIDDK NIH HHS / United States R01 DK048873 / DK / NIDDK NIH HHS / United States P30 DK063608 / DK / NIDDK NIH HHS / United States R01 DK056626 / DK / NIDDK NIH HHS / United States U01 DK112217 / DK / NIDDK NIH HHS / United States |