Glucagon blockade restores functional β-cell mass in type 1 diabetic mice and enhances function of human islets.
May Yun Wang,May Yun Wang,E. Danielle Dean,E. Danielle Dean,Ezekiel B. Quittner-Strom,Ezekiel B. Quittner-Strom,Yi Zhu,Yi Zhu,Yi Zhu,Kamrul H. Chowdhury,Zhuzhen Zhang,Shangang Zhao,Na Li,Reshing Ye,Young Chul Lee,Young Chul Lee,Yiyi Zhang,Shiuhwei Chen,Xinxin Yu,Xinxin Yu,Derek C. Leonard,Greg Poffenberger,Alison Von Deylen,S. Kay McCorkle,Amnon Schlegel,Kyle W. Sloop,Alexander M. Efanov,Ruth E. Gimeno,Philipp E. Scherer,Alvin C. Powers,Alvin C. Powers,Alvin C. Powers,Roger H Unger,Roger H Unger,William L. Holland,William L. Holland +35 more
TLDR
In this paper, the potential for a monoclonal antibody antagonist of the glucagon receptor (Ab-4) to maintain glucose homeostasis in type 1 diabetic rodents was evaluated.Abstract:
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.read more
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Pro-α-cell-derived β-cells contribute to β-cell neogenesis induced by antagonistic glucagon receptor antibody in type 2 diabetic mice
Xiaona Cui,Jin Feng,Tianjiao Wei,Liangbiao Gu,Dandan Wang,Shan Lang,Kun Yang,Jin Yang,Hai Yan,Rui Wei,Tianpei Hong +10 more
TL;DR: In this paper , the effects of glucagon receptor (GCGR) antagonism on β-cell neogenesis in type 2 diabetic (T2D) mice and explore the origins of the neogenic β-cells were investigated.
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The past, present, and future physiology and pharmacology of glucagon.
TL;DR: The history of glucagon from the past to the present and suggest some direction to the future of this field is described in this article , where the authors describe the history of the development of the glucagon receptor and its use in the treatment of type 2 diabetes.
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Regulation of α‐cell glucagon secretion: The role of second messengers
TL;DR: In this article , the impact of second messengers on α-cell electrical activity, intracellular Ca2+ dynamics and cell exocytosis was discussed, and the possibility that the interaction between different secondmessengers may play a key role in the glucose-regulation of glucagon secretion was highlighted.
Journal ArticleDOI
Regulation of α-cell glucagon secretion: The role of second messengers
TL;DR: The possibility that the interaction between different second messengers may play a key role in the glucose‐regulation of glucagon secretion is highlighted, highlighting the impact of second Messengers on α‐cell electrical activity, intracellular Ca2+ dynamics and cell exocytosis.
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Pancreatic alpha cell glucagon–liver FGF21 axis regulates beta cell regeneration in a mouse model of type 2 diabetes
Xiaona Cui,Jin Feng,Tianjiao Wei,Linxi Zhang,Shan Lang,Kun Yang,Jin Yang,Junling Liu,Michael Sterr,Heiko Lickert,Rui Wei,Tianpei Hong +11 more
TL;DR: In this article , the authors investigated the mechanism of beta cell regeneration induced by glucagon receptor antagonism in mice and showed that FGF21 levels in plasma and liver were upregulated by GCGR antagonism.
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William L. Holland,Russell A. Miller,Zhao V. Wang,Kai Sun,Brian M. Barth,Hai H. Bui,Kathryn Davis,Benjamin T. Bikman,Nils Halberg,Nils Halberg,Joseph M. Rutkowski,Mark R. Wade,Vincent M. Tenorio,Ming Shang Kuo,Joseph T. Brozinick,Bei B. Zhang,Morris J. Birnbaum,Scott A. Summers,Scott A. Summers,Scott A. Summers,Philipp E. Scherer +20 more
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Lower blood glucose, hyperglucagonemia, and pancreatic α cell hyperplasia in glucagon receptor knockout mice
Richard W. Gelling,Xueliang Du,Darwin S. Dichmann,John Rømer,H. Huang,Lingguang Cui,Silvana Obici,B. Tang,Jens J. Holst,Christian Fledelius,Peter B. Johansen,Luciano Rossetti,Linda A. Jelicks,Palle Serup,Erica Nishimura,Maureen J. Charron +15 more
TL;DR: The data indicate that glucagon is essential for maintenance of normal glycemia and postnatal regulation of islet and α and δ cell numbers and the lean phenotype of Gcgr−/− mice suggests glucagon action may be involved in the regulation of whole body composition.
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Insulin within islets is a physiologic glucagon release inhibitor.
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