Titre
Normal glucagon signaling and β-cell function after near-total α-cell ablation in adult mice.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Thorel, F.
Auteure/Auteur
Damond, N.
Auteure/Auteur
Chera, S.
Auteure/Auteur
Wiederkehr, A.
Auteure/Auteur
Thorens, B.
Auteure/Auteur
Meda, P.
Auteure/Auteur
Wollheim, C.B.
Auteure/Auteur
Herrera, P.L.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1939-327X
Statut éditorial
Publié
Date de publication
2011
Volume
60
Numéro
11
Première page
2872
Dernière page/numéro d’article
2882
Langue
anglais
Résumé
OBJECTIVEEvaluate whether healthy or diabetic adult mice can tolerate an extreme loss of pancreatic α-cells and how this sudden massive depletion affects β-cell function and blood glucose homeostasis.RESEARCH DESIGN AND METHODSWe generated a new transgenic model allowing near-total α-cell removal specifically in adult mice. Massive α-cell ablation was triggered in normally grown and healthy adult animals upon diphtheria toxin (DT) administration. The metabolic status of these mice was assessed in 1) physiologic conditions, 2) a situation requiring glucagon action, and 3) after β-cell loss.RESULTSAdult transgenic mice enduring extreme (98%) α-cell removal remained healthy and did not display major defects in insulin counter-regulatory response. We observed that 2% of the normal α-cell mass produced enough glucagon to ensure near-normal glucagonemia. β-Cell function and blood glucose homeostasis remained unaltered after α-cell loss, indicating that direct local intraislet signaling between α- and β-cells is dispensable. Escaping α-cells increased their glucagon content during subsequent months, but there was no significant α-cell regeneration. Near-total α-cell ablation did not prevent hyperglycemia in mice having also undergone massive β-cell loss, indicating that a minimal amount of α-cells can still guarantee normal glucagon signaling in diabetic conditions.CONCLUSIONSAn extremely low amount of α-cells is sufficient to prevent a major counter-regulatory deregulation, both under physiologic and diabetic conditions. We previously reported that α-cells reprogram to insulin production after extreme β-cell loss and now conjecture that the low α-cell requirement could be exploited in future diabetic therapies aimed at regenerating β-cells by reprogramming adult α-cells.
Sujets
PID Serval
serval:BIB_16B62B557AAA
PMID
Open Access
Oui
Date de création
2011-10-13T09:32:18.230Z
Date de création dans IRIS
2025-05-20T13:25:22Z
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Nom
BIB_16B62B557AAA.P001.pdf
Version du manuscrit
preprint
Taille
2.14 MB
Format
Adobe PDF
PID Serval
serval:BIB_16B62B557AAA.P001
URN
urn:nbn:ch:serval-BIB_16B62B557AAA7
Somme de contrôle
(MD5):5440287d48af0aaea27add621ec5ef45