Glucose Transporters Are Key Components of the Human Glucostat.

Autor:	Caspi I; Weill Cornell Graduate School of Medical Sciences, Weill Cornell Medicine, New York, NY.; Developmental Biology Program, Sloan Kettering Institute, New York, NY., Tremmel DM; Transplantation Division, Department of Surgery, University of Wisconsin-Madison, Madison, WI., Pulecio J; Developmental Biology Program, Sloan Kettering Institute, New York, NY., Yang D; Developmental Biology Program, Sloan Kettering Institute, New York, NY., Liu D; Developmental Biology Program, Sloan Kettering Institute, New York, NY.; Louis V. Gerstner Jr. Graduate School of Biomedical Sciences, Memorial Sloan-Kettering Cancer Center, New York, NY., Yan J; Developmental Biology Program, Sloan Kettering Institute, New York, NY.; Louis V. Gerstner Jr. Graduate School of Biomedical Sciences, Memorial Sloan-Kettering Cancer Center, New York, NY., Odorico JS; Transplantation Division, Department of Surgery, University of Wisconsin-Madison, Madison, WI., Huangfu D; Developmental Biology Program, Sloan Kettering Institute, New York, NY.
Jazyk:	angličtina
Zdroj:	Diabetes [Diabetes] 2024 Aug 01; Vol. 73 (8), pp. 1336-1351.
DOI:	10.2337/db23-0508
Abstrakt:	Mouse models are extensively used in metabolic studies. However, inherent differences between the species, notably their blood glucose levels, hampered data translation into clinical settings. In this study, we confirmed GLUT1 to be the predominantly expressed glucose transporter in both adult and fetal human β-cells. In comparison, GLUT2 is detected in a small yet significant subpopulation of adult β-cells and is expressed to a greater extent in fetal β-cells. Notably, GLUT1/2 expression in INS+ cells from human stem cell-derived islet-like clusters (SC-islets) exhibited a closer resemblance to that observed in fetal islets. Transplantation of primary human islets or SC-islets, but not murine islets, lowered murine blood glucose to the human glycemic range, emphasizing the critical role of β-cells in establishing species-specific glycemia. We further demonstrate the functional requirements of GLUT1 and GLUT2 in glucose uptake and insulin secretion through chemically inhibiting GLUT1 in primary islets and SC-islets and genetically disrupting GLUT2 in SC-islets. Finally, we developed a mathematical model to predict changes in glucose uptake and insulin secretion as a function of GLUT1/2 expression. Collectively, our findings illustrate the crucial roles of GLUTs in human β-cells, and identify them as key components in establishing species-specific glycemic set points. (© 2024 by the American Diabetes Association.)
Databáze:	MEDLINE
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