Редактирование: CCNA1 (раздел)

==Publications==

{{medline-entry
|title=Age-dependent human β cell proliferation induced by glucagon-like peptide 1 and calcineurin signaling.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28920919
|abstract=Inadequate pancreatic β cell function underlies type 1 and type 2 diabetes mellitus. Strategies to expand functional cells have focused on discovering and controlling mechanisms that limit the proliferation of human β cells. Here, we developed an engraftment strategy to examine age-associated human islet cell replication competence and reveal mechanisms underlying age-dependent decline of β cell proliferation in human islets. We found that exendin-4 (Ex-4), an agonist of the glucagon-like peptide 1 receptor (GLP-1R), stimulates human β cell proliferation in juvenile but not adult islets. This age-dependent responsiveness does not reflect loss of GLP-1R signaling in adult islets, since Ex-4 treatment stimulated insulin secretion by both juvenile and adult human β cells. We show that the mitogenic effect of Ex-4 requires calcineurin/nuclear factor of activated T cells (NFAT) signaling. In juvenile islets, Ex-4 induced expression of calcineurin/NFAT signaling components as well as target genes for proliferation-promoting factors, including [[NFATC1]], [[FOXM1]], and [[CCNA1]]. By contrast, expression of these factors in adult islet β cells was not affected by Ex-4 exposure. These studies reveal age-dependent signaling mechanisms regulating human β cell proliferation, and identify elements that could be adapted for therapeutic expansion of human β cells.
|mesh-terms=* Adult
* Aging
* Animals
* Calcineurin
* Cyclin A1
* Exenatide
* Female
* Forkhead Box Protein M1
* Glucagon-Like Peptide 1
* Glucagon-Like Peptide-1 Receptor
* Humans
* Insulin
* Insulin Secretion
* Insulin-Secreting Cells
* Male
* Mice, Inbred NOD
* Middle Aged
* NFATC Transcription Factors
* Peptides
* Signal Transduction
* Venoms

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5617654
}}