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

Nicolas Damond, Fabrizio Thorel, Julie S. Moyers, Maureen J. Charron, Patricia M. Vuguin, Alvin C. Powers, Pedro L. Herrera

Research output: Contribution to journalArticle

28 Citations (Scopus)

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 a-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.

Original languageEnglish (US)
Article numbere13828
JournaleLife
Volume5
Issue numberAPRIL2016
DOIs
StatePublished - Apr 19 2016

Fingerprint

Glucagon Receptors
Medical problems
Glucagon
Insulin
Streptozocin
Hyperglycemia
Diphtheria Toxin
Insulin Receptor
Ablation
Experimental Diabetes Mellitus
Animals
Cell- and Tissue-Based Therapy
Type 1 Diabetes Mellitus
Hyperplasia
Regeneration

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Medicine(all)
  • Neuroscience(all)

Cite this

Damond, N., Thorel, F., Moyers, J. S., Charron, M. J., Vuguin, P. M., Powers, A. C., & Herrera, P. L. (2016). Blockade of glucagon signaling prevents or reverses diabetes onset only if residual β-cells persist. eLife, 5(APRIL2016), [e13828]. https://doi.org/10.7554/eLife.13828

Blockade of glucagon signaling prevents or reverses diabetes onset only if residual β-cells persist. / Damond, Nicolas; Thorel, Fabrizio; Moyers, Julie S.; Charron, Maureen J.; Vuguin, Patricia M.; Powers, Alvin C.; Herrera, Pedro L.

In: eLife, Vol. 5, No. APRIL2016, e13828, 19.04.2016.

Research output: Contribution to journalArticle

Damond, N, Thorel, F, Moyers, JS, Charron, MJ, Vuguin, PM, Powers, AC & Herrera, PL 2016, 'Blockade of glucagon signaling prevents or reverses diabetes onset only if residual β-cells persist', eLife, vol. 5, no. APRIL2016, e13828. https://doi.org/10.7554/eLife.13828
Damond, Nicolas ; Thorel, Fabrizio ; Moyers, Julie S. ; Charron, Maureen J. ; Vuguin, Patricia M. ; Powers, Alvin C. ; Herrera, Pedro L. / Blockade of glucagon signaling prevents or reverses diabetes onset only if residual β-cells persist. In: eLife. 2016 ; Vol. 5, No. APRIL2016.
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