Heterogeneous endocrine cell composition defines human islet functional phenotypes.

Autor:	Evans-Molina C; Departments of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA.; Departments of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.; Departments of Anatomy, Cell Biology, and Physiology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.; Departments of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.; Departments of Center for Diabetes and Metabolic Diseases, Indiana University School of Medicine, Indianapolis, IN 46202, USA.; Departments of Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA.; Richard L. Roudebush VA Medical Center, Indianapolis, IN 46202, USA., Pettway YD; Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA., Saunders DC; Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA., Sharp SA; Department of Pediatrics, Stanford School of Medicine, Stanford, CA 94305, USA., Bate TS; Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA., Sun H; Department of Pediatrics, Stanford School of Medicine, Stanford, CA 94305, USA., Durai H; Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA., Mei S; Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA., Coldren A; Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA., Davis C; Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA., Reihsmann CV; Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA., Hopkirk AL; Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA., Taylor J; Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA., Bradley A; Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA., Aramandla R; Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA., Poffenberger G; Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA., Eskaros A; Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA., Jenkins R; Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA., Shi D; Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN 37232, USA., Kang H; Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN 37232, USA., Rajesh V; Department of Pediatrics, Stanford School of Medicine, Stanford, CA 94305, USA., Thaman S; Department of Pediatrics, Stanford School of Medicine, Stanford, CA 94305, USA., Feng F; Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA., Cartailler JP; Vanderbilt Center for Stem Cell Biology, Vanderbilt University, Nashville, TN 37232, USA., Powers AC; Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.; Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.; VA Tennessee Valley Healthcare System, Nashville, TN 37232, USA., Abraham K; Division of Diabetes, Endocrinology, & Metabolic Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Gloyn AL; Department of Pediatrics, Stanford School of Medicine, Stanford, CA 94305, USA.; Department of Genetics, Stanford School of Medicine, Stanford, CA, USA.; Stanford Diabetes Center, Stanford School of Medicine, Stanford, CA, USA., Niland JC; Department of Diabetes and Cancer Discovery Science, Arthur Riggs Diabetes and Metabolism Research Institute, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA., Brissova M; Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Nov 21. Date of Electronic Publication: 2024 Nov 21.
DOI:	10.1101/2024.11.20.623809
Abstrakt:	Phenotyping and genotyping initiatives within the Integrated Islet Distribution Program (IIDP), the largest source of human islets for research in the U.S., provide standardized assessment of islet preparations distributed to researchers, enabling the integration of multiple data types. Data from islets of the first 299 organ donors without diabetes, analyzed using this pipeline, highlights substantial heterogeneity in islet cell composition associated with hormone secretory traits, sex, reported race and ethnicity, genetically predicted ancestry, and genetic risk for type 2 diabetes (T2D). While α and β cell composition influenced insulin and glucagon secretory traits, the abundance of δ cells showed the strongest association with insulin secretion and was also associated with the genetic risk score (GRS) for T2D. These findings have important implications for understanding mechanisms underlying diabetes heterogeneity and islet dysfunction and may provide insight into strategies for personalized medicine and β cell replacement therapy. Competing Interests: DECLARATION OF INTERESTS A.L.G’s spouse is an employee of Genentech and holds stock options in Roche.
Databáze:	MEDLINE
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