气候变化领域集成服务门户(CCPortal): Glucagon blockade restores functional β-cell mass in type 1 diabetic mice and enhances function of human islets

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DOI	10.1073/pnas.2022142118
	Glucagon blockade restores functional β-cell mass in type 1 diabetic mice and enhances function of human islets
	Wang M.-Y.; Dean E.D.; Quittner-Strom E.; Zhu Y.; Chowdhury K.H.; Zhang Z.; Zhao S.; Li N.; Ye R.; Lee Y.; Zhang Y.; Chen S.; Yu X.; Leonard D.C.; Poffenberger G.; Deylen A.V.; McCorkle S.K.; Schlegel A.; Sloop K.W.; Efanov A.M.; Gimeno R.E.; Scherer P.E.; Powers A.C.; Unger R.H.; Holland W.L.
发表日期	2021
ISSN	00278424
卷号	118 期号:9
英文摘要	We evaluated the potential for a monoclonal antibody antagonist of the glucagon receptor (Ab-4) to maintain glucose homeostasis in type 1 diabetic rodents. We noted durable and sustained improvements in glycemia which persist long after treatment withdrawal. Ab-4 promoted β-cell survival and enhanced the recovery of insulin+ islet mass with concomitant increases in circulating insulin and C peptide. In PANIC-ATTAC mice, an inducible model of β-cell apoptosis which allows for robust assessment of β-cell regeneration following caspase-8-induced diabetes, Ab-4 drove a 6.7-fold increase in β-cell mass. Lineage tracing suggests that this restoration of functional insulin-producing cells was at least partially driven by α-cell-to-β-cell conversion. Following hyperglycemic onset in nonobese diabetic (NOD) mice, Ab-4 treatment promoted improvements in C-peptide levels and insulin+ islet mass was dramatically increased. Lastly, diabetic mice receiving human islet xenografts showed stable improvements in glycemic control and increased human insulin secretion. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Diabetes; Glucagon; Insulin; Islet; Regeneration
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180469
作者单位	Touchstone Diabetes Center, Department of Internal Medicine, University of Texas, Southwestern Medical Center, Dallas, TX 75390-8549, United States; Medical Service, Veterans Administration North Texas Health Care System, Dallas, TX 75216, United States; Division of Diabetes, Endocrinology and Metabolism, Vanderbilt University, Medical Center, Nashville, TN 37232, United States; Department of Molecular Physiology and Biophysics, Vanderbilt University, School of Medicine, Nashville, TN 37232, United States; Department of Nutrition and Integrative Physiology, University of Utah, College of Health, Salt Lake City, UT 84112, United States; Diabetes and Complications, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, United States; Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, United States; Division of Endocrinology, Metabolism, and Diabetes, Department of Internal Medicine, University of Utah, School of Medicine...
推荐引用方式 GB/T 7714	Wang M.-Y.,Dean E.D.,Quittner-Strom E.,et al. Glucagon blockade restores functional β-cell mass in type 1 diabetic mice and enhances function of human islets[J],2021,118(9).
APA	Wang M.-Y..,Dean E.D..,Quittner-Strom E..,Zhu Y..,Chowdhury K.H..,...&Holland W.L..(2021).Glucagon blockade restores functional β-cell mass in type 1 diabetic mice and enhances function of human islets.Proceedings of the National Academy of Sciences of the United States of America,118(9).
MLA	Wang M.-Y.,et al."Glucagon blockade restores functional β-cell mass in type 1 diabetic mice and enhances function of human islets".Proceedings of the National Academy of Sciences of the United States of America 118.9(2021).