RGD Reference Report - Ebselen treatment prevents islet apoptosis, maintains intranuclear Pdx-1 and MafA levels, and preserves ß-cell mass and function in ZDF rats. - Rat Genome Database

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Ebselen treatment prevents islet apoptosis, maintains intranuclear Pdx-1 and MafA levels, and preserves ß-cell mass and function in ZDF rats.

Authors: Mahadevan, Jana  Parazzoli, Susan  Oseid, Elizabeth  Hertzel, Ann V  Bernlohr, David A  Vallerie, Sara N  Liu, Chang-qin  Lopez, Melissa  Harmon, Jamie S  Robertson, R Paul 
Citation: Mahadevan J, etal., Diabetes. 2013 Oct;62(10):3582-8. doi: 10.2337/db13-0357. Epub 2013 Jun 25.
RGD ID: 13506744
Pubmed: PMID:23801580   (View Abstract at PubMed)
PMCID: PMC3781455   (View Article at PubMed Central)
DOI: DOI:10.2337/db13-0357   (Journal Full-text)

We reported earlier that ß-cell-specific overexpression of glutathione peroxidase (GPx)-1 significantly ameliorated hyperglycemia in diabetic db/db mice and prevented glucotoxicity-induced deterioration of ß-cell mass and function. We have now ascertained whether early treatment of Zucker diabetic fatty (ZDF) rats with ebselen, an oral GPx mimetic, will prevent ß-cell deterioration. No other antihyperglycemic treatment was given. Ebselen ameliorated fasting hyperglycemia, sustained nonfasting insulin levels, lowered nonfasting glucose levels, and lowered HbA1c levels with no effects on body weight. Ebselen doubled ß-cell mass, prevented apoptosis, prevented expression of oxidative stress markers, and enhanced intranuclear localization of pancreatic and duodenal homeobox (Pdx)-1 and v-maf musculoaponeurotic fibrosarcoma oncogene family, protein A (MafA), two critical insulin transcription factors. Minimal ß-cell replication was observed in both groups. These findings indicate that prevention of oxidative stress is the mechanism whereby ebselen prevents apoptosis and preserves intranuclear Pdx-1 and MafA, which, in turn, is a likely explanation for the beneficial effects of ebselen on ß-cell mass and function. Since ebselen is an oral antioxidant currently used in clinical trials, it is a novel therapeutic candidate to ameliorate fasting hyperglycemia and further deterioration of ß-cell mass and function in humans undergoing the onset of type 2 diabetes.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
diabetes mellitus treatmentISOMafa (Rattus norvegicus)13506744; 13506744 RGD 
diabetes mellitus treatmentIEP 13506744 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Mafa  (MAF bZIP transcription factor A)

Genes (Mus musculus)
Mafa  (MAF bZIP transcription factor A)

Genes (Homo sapiens)
MAFA  (MAF bZIP transcription factor A)


Additional Information