UNIGE document Scientific Article
previous document  unige:84018  next document
add to browser collection
Title

Blockade of glucagon signaling prevents or reverses diabetes onset only if residual β-cells persist

Authors
Moyers, Julie S
Charron, Maureen J
Vuguin, Patricia M
Powers, Alvin C
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
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

76 hits

59 downloads

Update

Deposited on : 2016-05-31

Export document
Format :
Citation style :