Wisp1 is a circulating factor that stimulates proliferation of adult mouse and human beta cells.
Aging
/ blood
Animals
CCN Intercellular Signaling Proteins
/ blood
Cell Proliferation
Cells, Cultured
Culture Media
/ metabolism
Diabetes Mellitus
/ therapy
Female
Humans
Insulin-Secreting Cells
/ physiology
Islets of Langerhans Transplantation
/ methods
Male
Mice
Mice, Knockout
Primary Cell Culture
/ methods
Proto-Oncogene Proteins
/ blood
Proto-Oncogene Proteins c-akt
/ metabolism
Recombinant Proteins
/ genetics
Signal Transduction
/ physiology
Weaning
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
25 11 2020
25 11 2020
Historique:
received:
13
02
2019
accepted:
16
10
2020
entrez:
26
11
2020
pubmed:
27
11
2020
medline:
15
12
2020
Statut:
epublish
Résumé
Expanding the mass of pancreatic insulin-producing beta cells through re-activation of beta cell replication has been proposed as a therapy to prevent or delay the appearance of diabetes. Pancreatic beta cells exhibit an age-dependent decrease in their proliferative activity, partly related to changes in the systemic environment. Here we report the identification of CCN4/Wisp1 as a circulating factor more abundant in pre-weaning than in adult mice. We show that Wisp1 promotes endogenous and transplanted adult beta cell proliferation in vivo. We validate these findings using isolated mouse and human islets and find that the beta cell trophic effect of Wisp1 is dependent on Akt signaling. In summary, our study reveals the role of Wisp1 as an inducer of beta cell replication, supporting the idea that the use of young blood factors may be a useful strategy to expand adult beta cell mass.
Identifiants
pubmed: 33239617
doi: 10.1038/s41467-020-19657-1
pii: 10.1038/s41467-020-19657-1
pmc: PMC7689468
doi:
Substances chimiques
CCN Intercellular Signaling Proteins
0
CCN4 protein, human
0
CCN4 protein, mouse
0
Culture Media
0
Proto-Oncogene Proteins
0
Recombinant Proteins
0
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
Types de publication
Journal Article
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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