東華大學圖書館 |

Language: English

Help

回圖書館首頁

手機版館藏查詢

Back

Switch To: Labeled | MARC Mode | ISBD

The Regulation of Cardiac Nrf2 Durin...

Thorwald, Max Andrew.

Linked to FindBook

Google Book

Amazon

博客來

The Regulation of Cardiac Nrf2 During an Acute Glucose Challenge and the Impact on Mitochondrial Function During Insulin Resistance and Type II Diabetes Mellitus.

Record Type:	Electronic resources : Monograph/item
Title/Author:	The Regulation of Cardiac Nrf2 During an Acute Glucose Challenge and the Impact on Mitochondrial Function During Insulin Resistance and Type II Diabetes Mellitus./
Author:	Thorwald, Max Andrew.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2018,
Description:	91 p.
Notes:	Source: Dissertations Abstracts International, Volume: 80-05, Section: B.
Contained By:	Dissertations Abstracts International80-05B.
Subject:	Molecular biology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10929893
ISBN:	9780438538191

The Regulation of Cardiac Nrf2 During an Acute Glucose Challenge and the Impact on Mitochondrial Function During Insulin Resistance and Type II Diabetes Mellitus.
Thorwald, Max Andrew.

The Regulation of Cardiac Nrf2 During an Acute Glucose Challenge and the Impact on Mitochondrial Function During Insulin Resistance and Type II Diabetes Mellitus. - Ann Arbor : ProQuest Dissertations & Theses, 2018 - 91 p.

Source: Dissertations Abstracts International, Volume: 80-05, Section: B.

Thesis (Ph.D.)--University of California, Merced, 2018.

This item must not be sold to any third party vendors.

During the progression of Type II diabetes hearts are under stress due to increases in oxidant production and contractile force from elevated blood pressure. Pre-diabetic and diabetic individuals undergo periods of hyperglycemia which contribute significantly to oxidant production while elevated blood pressure also contributes to the influx of oxidant production. The renin angiotensin system is responsible for blood pressure homeostasis and becomes chronically elevated during metabolic derangements. Furthermore, chronic low-grade inflammation mediated through NF-κB is present during the disease manifestation which has been reported to be antagonistic of Nrf2, a transcription factor with a wide array of cellular detoxifying genes. The objectives of these projects were to elucidate the impact a hyperglycemic event has on insulin resistant and diabetic hearts, the role of AT1 activation of mitochondrial function and antioxidant capacity, and the changes in NF-kB and Nrf2 signaling as type II diabetes progresses. In the first chapter we demonstrate that insulin resistant hearts experience mitochondrial dysfunction and increases in damage, while blocking the AT1 receptor increases Nrf2 binding to the electrophile response element during an acute glucose challenge. In the second chapter we demonstrate that diabetic hearts increase glutathione content in response to glucose and that antagonism of the AT1 receptor has beneficial impacts on Nrf2 related gene expression. We also demonstrate that non-diabetic animals increase Nrf2 related genes after a glucose bolus indicating that Nrf2 increases in response to glucose. The third chapter examines the relationship between cardiac Nrf2 and NF-κB during the progression of diabetes. Here we demonstrate that nuclear NF-κB content and acetylation increases rapidly as type II diabetes progresses and that nuclear Nrf2 content and acetylation is blunted. This is the first time that acute glucose challenges have been performed in in vivo during both insulin resistant and type II diabetic animals where blockade of the AT1 has been incorporated. Our findings contribute to the understanding of antioxidant defense during hyperglycemic events through the progression of type II diabetes. These studies illustrate the importance of antioxidant defense during even the early stages of insulin resistance and bolster the idea that antioxidant defense is impaired during hyperglycemic events.

ISBN: 9780438538191Subjects--Topical Terms:

517296
Molecular biology.
Subjects--Index Terms:

Glutathione

The Regulation of Cardiac Nrf2 During an Acute Glucose Challenge and the Impact on Mitochondrial Function During Insulin Resistance and Type II Diabetes Mellitus.
LDR:03767nmm a2200397 4500 001 2272273
005 20201105110009.5
008 220629s2018 ||||||||||||||||| ||eng d
020 $a 9780438538191
035 $a (MiAaPQ)AAI10929893
035 $a (MiAaPQ)ucmerced:10407
035 $a AAI10929893
040 $a MiAaPQ $c MiAaPQ
100 1 $a Thorwald, Max Andrew. $3 3549707
245 1 4 $a The Regulation of Cardiac Nrf2 During an Acute Glucose Challenge and the Impact on Mitochondrial Function During Insulin Resistance and Type II Diabetes Mellitus.
260 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 2018
300 $a 91 p.
500 $a Source: Dissertations Abstracts International, Volume: 80-05, Section: B.
500 $a Publisher info.: Dissertation/Thesis.
500 $a Advisor: Ortiz, Rudy M.
502 $a Thesis (Ph.D.)--University of California, Merced, 2018.
506 $a This item must not be sold to any third party vendors.
520 $a During the progression of Type II diabetes hearts are under stress due to increases in oxidant production and contractile force from elevated blood pressure. Pre-diabetic and diabetic individuals undergo periods of hyperglycemia which contribute significantly to oxidant production while elevated blood pressure also contributes to the influx of oxidant production. The renin angiotensin system is responsible for blood pressure homeostasis and becomes chronically elevated during metabolic derangements. Furthermore, chronic low-grade inflammation mediated through NF-κB is present during the disease manifestation which has been reported to be antagonistic of Nrf2, a transcription factor with a wide array of cellular detoxifying genes. The objectives of these projects were to elucidate the impact a hyperglycemic event has on insulin resistant and diabetic hearts, the role of AT1 activation of mitochondrial function and antioxidant capacity, and the changes in NF-kB and Nrf2 signaling as type II diabetes progresses. In the first chapter we demonstrate that insulin resistant hearts experience mitochondrial dysfunction and increases in damage, while blocking the AT1 receptor increases Nrf2 binding to the electrophile response element during an acute glucose challenge. In the second chapter we demonstrate that diabetic hearts increase glutathione content in response to glucose and that antagonism of the AT1 receptor has beneficial impacts on Nrf2 related gene expression. We also demonstrate that non-diabetic animals increase Nrf2 related genes after a glucose bolus indicating that Nrf2 increases in response to glucose. The third chapter examines the relationship between cardiac Nrf2 and NF-κB during the progression of diabetes. Here we demonstrate that nuclear NF-κB content and acetylation increases rapidly as type II diabetes progresses and that nuclear Nrf2 content and acetylation is blunted. This is the first time that acute glucose challenges have been performed in in vivo during both insulin resistant and type II diabetic animals where blockade of the AT1 has been incorporated. Our findings contribute to the understanding of antioxidant defense during hyperglycemic events through the progression of type II diabetes. These studies illustrate the importance of antioxidant defense during even the early stages of insulin resistance and bolster the idea that antioxidant defense is impaired during hyperglycemic events.
590 $a School code: 1660.
650 4 $a Molecular biology. $3 517296
650 4 $a Endocrinology. $3 610914
650 4 $a Biochemistry. $3 518028
650 4 $a Pathology. $3 643180
650 4 $a Physiology. $3 518431
653 $a Glutathione
653 $a Nf-kb
653 $a hyperglycemic events
690 $a 0307
690 $a 0409
690 $a 0487
690 $a 0571
690 $a 0719
710 2 $a University of California, Merced. $b Quantitative and Systems Biology. $3 3429142
773 0 $t Dissertations Abstracts International $g 80-05B.
790 $a 1660
791 $a Ph.D.
792 $a 2018
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10929893