| First Author | Motomura K | Year | 2024 |
| Journal | Diabetes | Volume | 73 |
| Issue | 1 | Pages | 75-92 |
| PubMed ID | 37871012 | Mgi Jnum | J:344399 |
| Mgi Id | MGI:7575708 | Doi | 10.2337/db23-0212 |
| Citation | Motomura K, et al. (2024) Single-Cell Transcriptome Profiling of Pancreatic Islets From Early Diabetic Mice Identifies Anxa10 for Ca2+ Allostasis Toward beta-Cell Failure. Diabetes 73(1):75-92 |
| abstractText | Type 2 diabetes is a progressive disorder denoted by hyperglycemia and impaired insulin secretion. Although a decrease in beta-cell function and mass is a well-known trigger for diabetes, the comprehensive mechanism is still unidentified. Here, we performed single-cell RNA sequencing of pancreatic islets from prediabetic and diabetic db/db mice, an animal model of type 2 diabetes. We discovered a diabetes-specific transcriptome landscape of endocrine and nonendocrine cell types with subpopulations of beta- and alpha-cells. We recognized a new prediabetic gene, Anxa10, that was induced by and regulated Ca2+ influx from metabolic stresses. Anxa10-overexpressed beta-cells displayed suppression of glucose-stimulated intracellular Ca2+ elevation and potassium-induced insulin secretion. Pseudotime analysis of beta-cells predicted that this Ca2+-surge responder cluster would proceed to mitochondria dysfunction and endoplasmic reticulum stress. Other trajectories comprised dedifferentiation and transdifferentiation, emphasizing acinar-like cells in diabetic islets. Altogether, our data provide a new insight into Ca2+ allostasis and beta-cell failure processes. ARTICLE HIGHLIGHTS: The transcriptome of single-islet cells from healthy, prediabetic, and diabetic mice was studied. Distinct beta-cell heterogeneity and islet cell-cell network in prediabetes and diabetes were found. A new prediabetic beta-cell marker, Anxa10, regulates intracellular Ca2+ and insulin secretion. Diabetes triggers beta-cell to acinar cell transdifferentiation. |
