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INS — MAFA
Pathways - manually collected, often from reviews:
Text-mined interactions from Literome
Matsuoka et al., Proc Natl Acad Sci U S A 2004
:
Here, we show that
MafA selectively
induces endogenous
insulin transcription in non-beta cells ... These results demonstrate that
MafA is a potent
insulin activator that is likely to function downstream of Nkx6.1 during islet insulin producing cell development
Pino et al., Mol Endocrinol 2005
:
These data indicate that glucose suppression of human
insulin promoter activity in INS-1 cells
involves reduced binding of
MafA to the A5/core
Harmon et al., J Biol Chem 2005
:
Additionally, transient transfection of PDX-1 or MafA cDNA into glucotoxic cells increased PDX-1 and MafA protein levels and individually increased insulin promoter activity ( untreated = 34 %, PDX-1 = 70 %, MafA = 78 % ; percentage of activity of early passage cells ), whereas the combined transfection of
MafA and PDX-1 completely
restored insulin promoter activity
Zhao et al., J Biol Chem 2005
:
The islet enriched
MafA , PDX-1, and BETA2 activators
contribute to both beta cell-specific and glucose-responsive
insulin gene transcription
Docherty et al., Biochem J 2005
:
PDX-1 was shown further to activate the endogenous insulin 1 gene in alphaTC1.6 cells, whereas
MafA activated the
insulin 2 gene ... In combination, PDX-1 and
MafA activated both
insulin genes
Zhang et al., Mol Cell Biol 2005
(Diabetes Mellitus) :
To analyze the
role of
MafA in
insulin transcription and glucose homeostasis in vivo, we generated MafA-deficient mice
Hagman et al., J Biol Chem 2005
:
Palmitate
inhibits insulin gene expression by altering PDX-1 nuclear localization and reducing
MafA expression in isolated rat islets of Langerhans ... Combined adenovirus mediated overexpression of PDX-1 and
MafA in islets completely
prevented the inhibition of
insulin gene expression by palmitate ... These results demonstrate that prolonged exposure of islets to palmitate
inhibits insulin gene transcription by impairing nuclear localization of PDX-1 and cellular expression of
MafA
Nishimura et al., Biochem J 2005
:
Surprisingly, instead of interfering with each other 's binding activity, the
MafA and the A2-binding factors co-operatively
activated insulin gene expression
Vanderford et al., J Biol Chem 2007
:
Within the pancreas,
MafA is exclusively expressed in the beta cells and is
involved in insulin gene transcription,
insulin secretion, and beta cell survival
Wang et al., Diabetologia 2007
(Insulinoma...) :
MAFA overproduction enhanced and its dominant negative mutant (
DN-MAFA )
diminished binding of the factor to the
insulin promoter, correlating with insulin mRNA levels and cellular protein content
Kaneto et al., Diabetes Res Clin Pract 2007
(Diabetes Mellitus) :
Furthermore,
MafA markedly
enhances insulin gene promoter activity and ameliorates glucose tolerance in diabetic mice, especially in the presence of PDX-1 and NeuroD
Aramata et al., Endocr J 2007
:
This review summarizes recent progress in determining the functions and
roles of
MafA in the regulation of
insulin gene transcription in beta-cells
Matsumura et al., Biochem Biophys Res Commun 2007
:
To investigate the relationship between MafA dependent transcriptional activation and TGF-beta signaling, we examined the effects of TGF-beta signal on
MafA dependent transactivation of the rat
insulin II gene promoter ( RIPII-251 ) and a synthetic MafA dependent promoter
Muniappan et al., BMC physiology 2007
:
Expression of either human insulin or the beta cell specific transcription factors PDX-1, NeuroD1 and
MafA in the Hepa1-6 cell line or primary liver cells via adenoviral gene transfer,
results in production and secretion of
insulin
Ogihara et al., Endocr J 2008
:
Coexpression of Nkx6.1 and Ngn3 induced endogenous expression of the insulin 2 gene, while coexpression of
Maf A and Ngn3
induced both
insulin 1 and 2 genes in AR42J-B13 cells
Kaneto et al., Frontiers in bioscience : a journal and virtual library 2008
(Hyperglycemia...) :
MafA is a recently isolated beta-cell-specific transcription factor and functions as a potent
activator of
insulin gene transcription
Artner et al., J Endocrinol 2008
:
MafA is a dedicated
activator of the
insulin gene in vivo ... Ectopic expression of
MafA , but not MafB,
promoted Insulin production ; however, neither MafA nor MafB were capable of inducing Glucagon
Nishimura et al., Dev Biol 2009
:
The transcription factor
MafA regulates glucose-responsive expression of
insulin
Wilson et al., Stem Cells 2009
:
In contrast to the endogenous promoter, an exogenous rat
INS promoter was
activated by expression of Pdx1 and
Mafa in hIPCs
Matsuoka et al., Diabetes 2010
(Diabetes Mellitus, Type 2) :
Importantly,
MafA overexpression
restored the
insulin promoter activity and protein levels that were suppressed by c-Jun
Noso et al., Diabetes 2010
(Diabetes Mellitus, Type 1...) :
Here, we report the
role of the insulin transactivator
MafA in the expression of
insulin in the thymus and susceptibility to type 1 diabetes ... Targeted disruption of
MafA reduced thymic
Ins2 expression and induced autoantibodies against pancreatic islets
Aguayo-Mazzucato et al., Diabetologia 2011
:
Mafa expression
enhances glucose-responsive
insulin secretion in neonatal rat beta cells
Chen et al., Assay Drug Dev Technol 2011
:
Forced expression ( between days 16 and 25 ) of
MafA , a pancreatic maturation factor,
resulted in enhanced expression of
insulin genes, glucose transporter 2 and glucokinase, and glucose-responsive insulin secretion
You et al., Diabetes & metabolism journal 2011
:
The adenovirus mediated overexpression of PDX-1, BETA2/NeuroD and
MafA induced
insulin gene expression in NPCCs, but not in adult pig pancreatic cells
Vargas et al., PloS one 2011
:
When injected in utero into living mouse embryos,
TAT-MafA significantly up-regulates target genes and
induces enhanced
insulin production as well as cytoarchitectural changes consistent with faster islet maturation
Lu et al., Biochemistry 2012
:
MafA is a proto-oncoprotein and is
critical for
insulin gene expression in pancreatic ß-cells
Zhou et al., Cells Tissues Organs 2013
:
Expression of
MAFA was
sufficient to induce
insulin mRNA expression in nhpAFS cell lines, whereas a combination of MAFA, PDX1 and NGN3 further induced insulin expression, and also induced the expression of other important endocrine cell genes such as glucagon, NEUROD1, NKX2.2, ISL1 and PCSK2
El Khattabi et al., Mol Endocrinol 2013
:
Furthermore the expression of alanine ( A )
134-MafA , but not A57-MafA,
reduced the oxidative stress mediated loss of glucose stimulated
insulin secretion, which was independent of p38 MAPK action on protein kinase D, a regulator of insulin secretion
Nogueira et al., PLoS Genet 2013
(Diabetes Mellitus, Type 1...) :
GLIS3 knockdown ( KD ) in INS-1E cells, primary FACS purified rat beta cells, and human islet cells decreased expression of
MafA , Ins2, and Glut2 and
inhibited glucose oxidation and
insulin secretion, confirming the role of this transcription factor for the beta cell differentiated phenotype