Abstract
MafA, a recently isolated pancreatic beta-cell-specific transcription factor, is a potent activator of insulin gene transcription. In this study, we show that MafA overexpression, together with PDX-1 (pancreatic and duodenal homeobox factor-1) and NeuroD, markedly increases insulin gene expression in the liver. Consequently, substantial amounts of insulin protein were induced by such combination. Furthermore, in streptozotocin-induced diabetic mice, MafA overexpression in the liver, together with PDX-1 and NeuroD, dramatically ameliorated glucose tolerance, while combination of PDX-1 and NeuroD was much less effective. These results suggest a crucial role of MafA as a novel therapeutic target for diabetes.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adenoviridae / genetics
-
Animals
-
Basic Helix-Loop-Helix Transcription Factors
-
Blotting, Northern
-
Cell Line
-
DNA-Binding Proteins / biosynthesis
-
Diabetes Mellitus / therapy*
-
Diabetes Mellitus, Experimental
-
Glucose / metabolism
-
Homeodomain Proteins / biosynthesis
-
Humans
-
Immunohistochemistry
-
Insulin / metabolism
-
Liver / metabolism
-
Luciferases / metabolism
-
Maf Transcription Factors, Large
-
Male
-
Mice
-
Mice, Inbred C57BL
-
Streptozocin / pharmacology
-
Time Factors
-
Trans-Activators / biosynthesis
-
Trans-Activators / metabolism
-
Trans-Activators / physiology*
-
Transfection
Substances
-
Basic Helix-Loop-Helix Transcription Factors
-
DNA-Binding Proteins
-
Homeodomain Proteins
-
Insulin
-
MAFA protein, human
-
Maf Transcription Factors, Large
-
NEUROD1 protein, human
-
Neurod1 protein, mouse
-
Trans-Activators
-
pancreatic and duodenal homeobox 1 protein
-
Streptozocin
-
Luciferases
-
Glucose