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Mechanisms of transcriptional regula...

Maganti, Aarthi Vijaykumar.

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Mechanisms of transcriptional regulation in the maintenance of beta cell function.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Mechanisms of transcriptional regulation in the maintenance of beta cell function./
作者:	Maganti, Aarthi Vijaykumar.
面頁冊數:	155 p.
附註:	Source: Dissertation Abstracts International, Volume: 76-09(E), Section: B.
Contained By:	Dissertation Abstracts International76-09B(E).
標題:	Physiology. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3703858
ISBN:	9781321759235

Mechanisms of transcriptional regulation in the maintenance of beta cell function.
Maganti, Aarthi Vijaykumar.

Mechanisms of transcriptional regulation in the maintenance of beta cell function. - 155 p.

Source: Dissertation Abstracts International, Volume: 76-09(E), Section: B.

Thesis (Ph.D.)--Indiana University, 2015.

The islet beta cell is central to the maintenance of glucose homeostasis as the beta cell is solely responsible for the synthesis of Insulin. Therefore, better understanding of the molecular mechanisms governing beta cell function is crucial to designing therapies for diabetes. Pdx1, the master transcription factor of the beta cell, is required for the synthesis of proteins that maintain optimal beta cell function such as Insulin and glucose transporter type 2. Previous studies showed that Pdx1 interacts with the lysine methyltransferase Set7/9, relaxing chromatin and increasing transcription. Because Set7/9 also methylates non-histone proteins, I hypothesized that Set7/9-mediated methylation of Pdx1 increases its transcriptional activity. I showed that recombinant and cellular Pdx1 protein is methylated at two lysine residues, Lys123 and Lys131. Lys131 is involved in Set7/9 mediated augmented transactivation of Pdx1 target genes. Furthermore, beta cell-specific Set7/9 knockout mice displayed glucose intolerance and impaired insulin secretion, accompanied by a reduction in the expression of Pdx1 target genes. Our results indicate a previously unappreciated role for Set7/9 in the maintenance of Pdx1 activity and beta cell function. beta cell function is regulated on both the transcriptional and translational levels. beta cell function is central to the development of type 1 diabetes, a disease wherein the beta cell is destroyed by immune cells. Although the immune system is considered the primary instigator of the disease, recent studies suggest that defective beta cells may initiate the autoimmune response. I tested the hypothesis that improving beta cell function would reduce immune infiltration of the islet in the NOD mouse, a mouse model of spontaneous type 1 diabetes. Prediabetic NOD mice treated with pioglitazone, a drug that improves beta cell function, displayed an improvement in beta cell function, a reduction in beta cell death, accompanied by reductions in beta cell autoimmunity, indicating that beta cell dysfunction assists in the development of type 1 diabetes. Therefore, understanding the molecular mechanisms involved in beta cell function is essential for the development of therapies for diabetes.

ISBN: 9781321759235Subjects--Topical Terms:

518431
Physiology.

Mechanisms of transcriptional regulation in the maintenance of beta cell function.
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