Year: 2014
Type: article
Abstract: The large Maf transcription factors, MafA and MafB, are expressed with distinct spatial-temporal patterns in rodent islet cells. Analysis of Mafa(-/-) and pancreas-specific Mafa(∆panc) deletion mutant mice demonstrated a primary role for MafA in adult β-cell activity, different from the embryonic importance of MafB. Our interests here were to precisely define when MafA became functionally significant to β-cells, to determine how this was affected by the brief period of postnatal MafB production, and to identify genes regulated by MafA during this period. We found that islet cell organization, β-cell mass, and β-cell function were influenced by 3 weeks of age in Mafa(Δpanc) mice and compromised earlier in Mafa(Δpanc);Mafb(+/-) mice. A combination of genome-wide microarray profiling, electron microscopy, and metabolic assays were used to reveal mechanisms of MafA control. For example, β-cell replication was produced by actions on cyclin D2 regulation, while effects on granule docking affected first-phase insulin secretion. Moreover, notable differences in the genes regulated by embryonic MafB and postnatal MafA gene expression were found. These results not only clearly define why MafA is an essential transcriptional regulator of islet β-cells, but also why cell maturation involves coordinated actions with MafB.
Source: Diabetes
DOI: 10.2337/db13-1001
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Awards: G1045987153, G1103614030, G1227504828, Eunice Kennedy Shriver Intellectual and Developmental Disability Research Center, G1278377566, G1344704808, G150953014, G200055243, G2019238319, G2098294812, G2165376562, G2304076072, G281443759, G286871808, G2906896244, G2940777275, G2999437633, G3134821522, G3357049595, G35732448, G3722609264, G3989539122, Vanderbilt Mouse Metabolic Phenotyping Center, G4106985451, Multi-cellular Interactions and Dynamics underlying Insulin Secretion, G4513176822, G5021276694, G6007137191, Dynamics of Pancreatic Islet Function, G6555946479, G6845279160, G7018272708, G725763919, G79480885, Molecular and Cellular Basis for Digestive Diseases
OpenAlex ID: W2037554972