en
Scientific article
Open access
English

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

Published ineLife, vol. 5
Publication date2016
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.

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. doi: 10.7554/eLife.13828
Main files (1)
Article (Published version)
accessLevelPublic
Identifiers
ISSN of the journal2050-084X
478views
263downloads

Technical informations

Creation05/26/2016 4:09:00 PM
First validation05/26/2016 4:09:00 PM
Update time03/15/2023 12:23:30 AM
Status update03/15/2023 12:23:30 AM
Last indexation01/16/2024 8:53:57 PM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack