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Title

Blockade of glucagon signaling prevents or reverses diabetes onset only if residual β-cells persist
Authors
Damond, Nicolas
Thorel, Fabrizio
Moyers, Julie S
Charron, Maureen J
Vuguin, Patricia M
Powers, Alvin C
Herrera, Pedro Luis
Published in eLife. 2016, vol. 5
Abstract Glucagon secretion dysregulation in diabetes fosters hyperglycemia. Recent studies report that mice lacking glucagon receptor (Gcgr(-/-)) do not develop diabetes following streptozotocin (STZ)-mediated ablation of insulin-producing β-cells. Here, we show that diabetes prevention in STZ-treated Gcgr(-/-) animals requires remnant insulin action originating from spared residual β-cells: these mice indeed became hyperglycemic after insulin receptor blockade. Accordingly, Gcgr(-/-) mice developed hyperglycemia after induction of a more complete, diphtheria toxin (DT)-induced β-cell loss, a situation of near-absolute insulin deficiency similar to type 1 diabetes. In addition, glucagon deficiency did not impair the natural capacity of α-cells to reprogram into insulin production after extreme β-cell loss. α-to-β-cell conversion was improved in Gcgr(-/-) mice as a consequence of α-cell hyperplasia. Collectively, these results indicate that glucagon antagonism could i) be a useful adjuvant therapy in diabetes only when residual insulin action persists, and ii) help devising future β-cell regeneration therapies relying upon α-cell reprogramming.
Identifiers
PMID: 27092792
Full text
Article (Published version) (2.4 MB) - public document Free access
Structures
Faculté de médecine / Section de médecine fondamentale / Département de médecine génétique et développement
Research group Types cellulaires pancréatiques pendant l'ontogénèse (522)
Citation
(ISO format) 		DAMOND, Nicolas et al. Blockade of glucagon signaling prevents or reverses diabetes onset only if residual β-cells persist. In: eLife, 2016, vol. 5. https://archive-ouverte.unige.ch/unige:84018

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Deposited on : 2016-05-31

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