摘要 :
Pancreatic beta-cell-specific insulin gene expression is regulated by a variety of pancreatic transcription factors and the conserved A3, C1 and E1 elements in the insulin gene enhancer region are very important for activation of ...
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Pancreatic beta-cell-specific insulin gene expression is regulated by a variety of pancreatic transcription factors and the conserved A3, C1 and E1 elements in the insulin gene enhancer region are very important for activation of insulin gene. Indeed, PDX-1 binding to the A3 element and NeuroD binding to the E1 element are crucial for insulin gene transcription. Recently, C1 element-binding transcription factor was identified as MafA, which is a basic-leucine zipper transcription factor and functions as a potent transactivator for the insulin gene. Under diabetic conditions, chronic hyperglycemia gradually deteriorates pancreatic beta-cell function, which is accompanied by decreased expression and/or DNA binding activities of MafA and PDX-1. Furthermore, MafA overexpression, together with PDX-1 and NeuroD, markedly induces insulin biosynthesis in various non-beta-cells and thereby is a useful tool to efficiently induce insulin-producing surrogate beta-cells. These results suggest that MafA plays a crucial role in pancreatic beta-cells and could be a novel therapeutic target for diabetes.
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摘要 :
A decrease in the number of functioning pancreatic beta-cells and insufficient insulin biosynthesis and/or secretion are the hallmarks of diabetes. Therefore, the identification of alternative sources to induce insulin-producing s...
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A decrease in the number of functioning pancreatic beta-cells and insufficient insulin biosynthesis and/or secretion are the hallmarks of diabetes. Therefore, the identification of alternative sources to induce insulin-producing surrogate beta-cells is of great importance. For the induction of insulin-producing cells from various cells and/or tissues, it is useful to mimic and reproduce expression alterations of various pancreatic transcription factors observed during normal pancreas development and to induce key pancreatic transcription factors which have the potency to induce insulin and other beta-cell-related genes. MafA, PDX-1 and NeuroD directly bind to the insulin gene promoter and function as very important transcription factors in pancreatic beta-cell differentiation and mature beta-cell function. The combination of MafA, PDX-1 and NeuroD markedly induces insulin biosynthesis in various non-beta-cells and thereby is a useful tool to efficiently induce insulin-producing surrogate beta-cells.
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