RGD Reference Report - Regulation of MafA expression in pancreatic beta-cells in db/db mice with diabetes. - Rat Genome Database

RGD Reference Report - Regulation of MafA expression in pancreatic beta-cells in db/db mice with diabetes. - Rat Genome Database

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Regulation of MafA expression in pancreatic beta-cells in db/db mice with diabetes.
Authors:	Matsuoka, Taka-aki Kaneto, Hideaki Miyatsuka, Takeshi Yamamoto, Tsunehiko Yamamoto, Kaoru Kato, Ken Shimomura, Iichiro Stein, Roland Matsuhisa, Munehide
Citation:	Matsuoka TA, etal., Diabetes. 2010 Jul;59(7):1709-20. doi: 10.2337/db08-0693. Epub 2010 Apr 27.
RGD ID:	13506745
Pubmed:	PMID:20424231 (View Abstract at PubMed)
PMCID:	PMC2889771 (View Article at PubMed Central)
DOI:	DOI:10.2337/db08-0693 (Journal Full-text)
OBJECTIVE: Islet beta-cells loose their ability to synthesize insulin under diabetic conditions, which is at least partially due to the decreased activity of insulin transcription factors such as MafA. Although an in vitro study showed that reactive oxygen species (ROS) decrease MafA expression, the underlying mechanism still remains unclear. In this study, we examined the effects of c-Jun, which is known to be upregulated by ROS, on the expression of MafA under diabetic conditions. RESEARCH DESIGN AND METHODS: To examine the protein levels of MafA and c-Jun, we performed histological analysis and Western blotting using diabetic db/db mice. In addition, to evaluate the possible effects of c-Jun on MafA expression, we performed adenoviral overexpression of c-Jun in the MIN6 beta-cell line and freshly isolated islets. RESULTS MafA expression was markedly decreased in the islets of db/db mice, while in contrast c-Jun expression was increased. Costaining of these factors in the islets of db/db mice clearly showed that MafA and insulin levels are decreased in c-Jun-positive cells. Consistent with these results, overexpression of c-Jun significantly decreased MafA expression, accompanied by suppression of insulin expression. Importantly, MafA overexpression restored the insulin promoter activity and protein levels that were suppressed by c-Jun. These results indicate that the decreased insulin biosynthesis induced by c-Jun is principally mediated by the suppression of MafA activity. CONCLUSIONS: It is likely that the augmented expression of c-Jun in diabetic islets decreases MafA expression and thereby reduces insulin biosynthesis, which is often observed in type 2 diabetes.

Only show annotations with direct experimental evidence (0 objects hidden)

Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
MAFA	Human	type 2 diabetes mellitus		ISO	RGD:1557163	protein:decreased expression:beta cells of pancrea	RGD
Mafa	Mouse	type 2 diabetes mellitus		IEP		protein:decreased expression:beta cells of pancrea	RGD
Mafa	Rat	type 2 diabetes mellitus		ISO	RGD:1557163	protein:decreased expression:beta cells of pancrea	RGD

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)