dc.creator | Conrad, Elizabeth Elrod | |
dc.date.accessioned | 2020-08-22T21:13:23Z | |
dc.date.available | 2017-10-20 | |
dc.date.issued | 2015-10-20 | |
dc.identifier.uri | https://etd.library.vanderbilt.edu/etd-10162015-094156 | |
dc.identifier.uri | http://hdl.handle.net/1803/14322 | |
dc.description.abstract | Analysis of MafB-/- mice suggested that this transcription factor was essential to islet α- and β-cell formation during development, although the postnatal physiological impact could not be studied because these mutants died due to problems in neural development. Pancreas-wide mutant mice were generated by crossing MafBfl/fl mice with transgenic Pancreatic and duodenal homeobox 1 (Pdx1) driven-Cre mice to compare the postnatal significance of MafB (MafBΔpanc) and MafA/B (MafABΔpanc) to deficiencies associated with the related, β-cell-enriched MafA mutant (MafAΔpanc). Insulin+ cell production and β-cell activity was merely delayed in MafBΔpanc islets until MafA was comprehensively expressed, although MafABΔpanc mice died soon after birth from hyperglycemia. However, glucose-induced glucagon secretion was compromised in adult MafBΔpanc islet α-cells. Based upon these results, we conclude that MafB alone is important to islet α-cell activity, and not β-cell function in rodents. Interestingly, a notable difference between mice and humans is that MAFB is coexpressed with MAFA in adult human islet β-cells. In fact, we found that non-human primate (NHP) islet α- and β-cells also produce MAFB, implying that MAFB represents a unique functional signature of the primate islet β-cell. Stimulated insulin secretion experiments in the human β-cell line, EndoC-βH1, suggest that MAFB impacts cAMP-induced insulin secretion in the primate β-cell.
Interestingly, MafB expression is silenced soon after birth in the rodent β-cell, only to be induced in a subset of maternal β-cells during pregnancy. Notably, the metabolic demands of pregnancy involve increases in β-cell mass and function. Our analysis of β-cell-specific MafB mutant (MafBΔβ) mice, generated by crossing MafBfl/fl mice with Rat Insulin Promoter (RIP)-Cre transgenic mice, suggests a specific role for MafB in β-cell proliferation during pregnancy. This thesis work sheds new light on the role of MafB in β-cells during pregnancy and its novel importance in primates. | |
dc.format.mimetype | application/pdf | |
dc.subject | pancreas | |
dc.subject | islets | |
dc.subject | diabetes | |
dc.subject | beta cells | |
dc.subject | transcription factors | |
dc.title | Examining the roles of MafB in the pancreatic islet | |
dc.type | dissertation | |
dc.contributor.committeeMember | Wenbiao Chen | |
dc.contributor.committeeMember | Mark Magnuson | |
dc.contributor.committeeMember | Guoqiang Gu | |
dc.contributor.committeeMember | Roland Stein | |
dc.type.material | text | |
thesis.degree.name | PHD | |
thesis.degree.level | dissertation | |
thesis.degree.discipline | Molecular Physiology and Biophysics | |
thesis.degree.grantor | Vanderbilt University | |
local.embargo.terms | 2017-10-20 | |
local.embargo.lift | 2017-10-20 | |
dc.contributor.committeeChair | Maureen Gannon | |