Hartman Institute for Therapeutic Organ Regeneration

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

TitleA beta cell subset with enhanced insulin secretion and glucose metabolism is reduced in type 2 diabetes.
Publication TypeJournal Article
Year of Publication2023
AuthorsRubio-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
JournalNat Cell Biol
Volume25
Issue4
Pagination565-578
Date Published2023 Apr
ISSN1476-4679
KeywordsAnimals, 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>

DOI10.1038/s41556-023-01103-1
Alternate JournalNat Cell Biol
PubMed ID36928765
PubMed Central IDPMC10449536
Grant ListR01 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
P30 DK063608 / DK / NIDDK NIH HHS / United States
R01 DK056626 / DK / NIDDK NIH HHS / United States
U01 DK112217 / DK / NIDDK NIH HHS / United States

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Hartman Institute for Therapeutic Organ Regeneration
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