2. Insulin is a protein hormone that is critical for reducing the level of gluco

Question

2. Insulin is a protein hormone that is critical for reducing the level of glucose in the blood. Insulin is produced by beta-cells in the pancreas and the expression of the insulin gene is controlled by three regulatory transcription factors that are specific to the insulin gene. In addition, high levels of glucose in the blood increase the production of pre-mRNA molecules from the insulin gene a. Explain how the three regulatory transcription factors might be involved in regulating expression of the insulin gene only in pancreatic beta-cells. (1 point) b. Do you expect that glucose is acting as an enhancer, a transcription factor, or an effector molecule in this gene regulation system? Explain your answer. (1 point)

Explanation / Answer

In the mature pancreas, transcription factors play a role in achieving glucose homeostasis by regulating the expression of key genes involved in maintaining the -cell phenotype, most notably the insulin gene.
Pdx-1 (also known as Ipf-1, Idx-1, Iuf-1, and Stf-1) is considered to be the key transcription factor involved in early pancreatic development, -cell differentiation and maintenance of the mature -cell. Pdx-1 directly regulates insulin transcription (i.e., the insulin gene is a direct downstream target of Pdx-1) through formation of a complex with transcriptional co-activators on the proximal insulin promoter.
NeuroD1 (or 2) is a key transcription factor required for pancreatic development and endocrine cell differentiation. Pdx-1, forms a heterodimer complex with NeuroD1 and interacts synergistically to stimulate promoter activity.
MafA plays an important role in maintenance of -cell function. This basic leucine zipper transcription factor is reportedly found only in the -cells of the pancreas. MafA expression in the liver, together with Pdx-1 and NeuroD1, markedly induces insulin gene transcription. MafA overexpression, together with Pdx-1 and NeuroD1, drastically induces insulin production in the liver.

Glucose acts as an effector molecule in the regulation of expression of insulin gene. Glucose controls all steps of insulin gene expression, including transcription, preRNA splicing, and mRNA stability. When glucose level is high it binds to Pdx-1, the key transcription factor for the synthesis of insulin and activates it thereby initiating the production of insulin. Similarly, when the level of blood glucose decreases, the insulin production is also decreased.

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