Circadian Rhythm Disorder and the Protective Effects of Intermittent Fasting at Night in Diabetes

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Material Information

Title:
Circadian Rhythm Disorder and the Protective Effects of Intermittent Fasting at Night in Diabetes
Physical Description:
1 online resource (147 p.)
Language:
english
Creator:
Yan, Yuanqing
Publisher:
University of Florida
Place of Publication:
Gainesville, Fla.
Publication Date:

Thesis/Dissertation Information

Degree:
Doctorate ( Ph.D.)
Degree Grantor:
University of Florida
Degree Disciplines:
Genetics and Genomics
Committee Chair:
GRANT,MARIA A
Committee Co-Chair:
DERENDORF,HARTMUT C
Committee Members:
CHANG,LUNG-JI
SEGAL,MARK STUART

Subjects

Subjects / Keywords:
circadian -- diabetes -- dicer -- hscs -- if
Genetics and Genomics -- Dissertations, Academic -- UF
Genre:
Genetics and Genomics thesis, Ph.D.
bibliography   ( marcgt )
theses   ( marcgt )
government publication (state, provincial, terriorial, dependent)   ( marcgt )
born-digital   ( sobekcm )
Electronic Thesis or Dissertation

Notes

Abstract:
Hematopoieticstem cells (HSCs) are crucial to repair the injured vessels in diabetes. The release of HSCs follows circadian oscillation and is driven by the norepinephrine secreted by sympathetic nervous system. We demonstrate that the secretion of norepinephrine into blood follows circadian oscillation, but not the number of HSCs in diabetes. Using Pk/Pd approach, the mathematical models describing the circadian oscillation of plasma norepinephrine concentration and the release of HSCs driven by norepinephrine were built. These mathematical models could provide a valuable tool to develop novel therapeutics approaches against diabetes. Circadian rhythm is established by circadian clock, which including BMAL1, CLOCK, PER1-3 and CRY1-2. Circadian rhythm is controlled at both a transcriptional and post-transcriptional level suggesting the role of microRNA (miRNA) and double-stranded RNA (dsRNA) in this process. Endonuclease Dicer controls miRNA and dsRNA processing, however the role of Dicer in circadian regulation is not known. We demonstrate robust diurnal oscillations of Dicer expression in central and peripheral clock control systems.  The Dicer oscillations were either reduced or phase shifted with aging and Type 2 diabetes.  The decrease and phase shift of Dicer expression was associated with a similar decrease and phase shift of miRNAs146a and 125a-5p and with an increase in toxic Alu RNA, which indicated that the metabolic disease and aging-associated complications were associated with epigenetic dys-regulations. To correct the circadian disruption in T2D, db/db mice were restricted to intermittent fasting(IF) at night for 6 months. Long term IF at night reduced the amount of food intake, lose the body weight, increased the survival rate but did not change the glycated hematoglubolin level. The diabetic retinopathy and neuropathy were corrected by long term IF at night. Long term IF at night restored the altered circadian pattern of HSCs number, HSCs cell migration capability and circadian clock gene expression into normal control levels. In addition, long term IF at night increased eNOS expression, had anti-inflammation effect, sensitized insulin activity and regulated lipid metabolism. All these protective effects implied that by simply changing the time and amount of food intake the diabetic complications could be prevented.
General Note:
In the series University of Florida Digital Collections.
General Note:
Includes vita.
Bibliography:
Includes bibliographical references.
Source of Description:
Description based on online resource; title from PDF title page.
Source of Description:
This bibliographic record is available under the Creative Commons CC0 public domain dedication. The University of Florida Libraries, as creator of this bibliographic record, has waived all rights to it worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law.
Statement of Responsibility:
by Yuanqing Yan.
Thesis:
Thesis (Ph.D.)--University of Florida, 2013.
Local:
Adviser: GRANT,MARIA A.
Local:
Co-adviser: DERENDORF,HARTMUT C.
Electronic Access:
RESTRICTED TO UF STUDENTS, STAFF, FACULTY, AND ON-CAMPUS USE UNTIL 2015-12-31

Record Information

Source Institution:
UFRGP
Rights Management:
Applicable rights reserved.
Classification:
lcc - LD1780 2013
System ID:
UFE0046107:00001