Repository logo
 

Nesfatin-1 and Nesfatin-1-Like Peptide (NLP) Regulation of Energy Balance in Mice

dc.contributor.advisorUnniappan, Suraj
dc.contributor.committeeMemberMacphee, Daniel
dc.contributor.committeeMemberArnason, Terra
dc.contributor.committeeMemberLoewen, Matthew
dc.contributor.committeeMemberLeung, Adelaine
dc.creatorRamesh, Naresh
dc.creator.orcid0000-0002-5287-133X
dc.date.accessioned2019-06-06T21:18:39Z
dc.date.available2022-08-06T06:05:08Z
dc.date.created2019-05
dc.date.issued2019-06-06
dc.date.submittedMay 2019
dc.date.updated2019-06-06T21:18:39Z
dc.description.abstractWhole-body energy homeostasis is regulated by the endocrine system via a spectrum of hormones. Nucleobindin-1 and -2 (NUCB1 and NUCB2) are multi-domain calcium and DNA binding proteins. Nesfatin-1 encoded in NUCB2 is a multifunctional peptide with insulinotropic, glucoregulatory, fat influencing, cardiovascular and reproductive functions. While nesfatin-1 modulates enteric hormones, whether it is indispensable for normal enteric hormone milieu is unclear. Nesfatin-1 stimulates glucose-stimulated insulin secretion. It is abundantly expressed in the intestinal submucosa. However, its direct actions on intestinal glucose uptake are unknown. In pancreas, nesfatin-1 is exclusive to the β cells of islets. Whole-body disruption of NUCB2/nesfatin-1 in mice displays a sexually dimorphic effect, with alterations in body weight, food intake and energy homeostasis. How critical are β cell specific nesfatin-1 in glucose and energy homeostasis? Similarly, NUCB1 encodes a nesfatin-1-like peptide (NLP) that is insulinotropic. Whether NLP is a naturally occurring endogenous peptide remains unknown. The central hypothesis of this thesis research is that nesfatin-1 is crucial for enteric hormone milieu, intestinal glucose absorption, whole-body energy homeostasis, and NLP is an endogenous peptide. This thesis research led to four major findings. First, it was found that mice lacking NUCB2/nesfatin-1 had altered enteric hormone expression. Second, it was determined that lack of nesfatin-1 modulates major intestinal glucose transporters in a region-specific manner, and influences intestinal glucose transport. Third, the lack of nesfatin-1 in β cells alters glucose tolerance and metabolic parameters and the effects display sexual dimorphism. Fourth, naturally occurring NLP was identified as a metabolic peptide. Together, this research provides new information on the essential role of endogenous nesfatin-1 on energy homeostasis and establishes NLP as a naturally occurring bioactive peptide.
dc.format.mimetypeapplication/pdf
dc.identifier.urihttp://hdl.handle.net/10388/12116
dc.subjectNucleobindin, Nesfatin-1, Nesfatin-1-like peptide, Enteric hormones, Glucose transporter, Energy balance.
dc.titleNesfatin-1 and Nesfatin-1-Like Peptide (NLP) Regulation of Energy Balance in Mice
dc.typeThesis
dc.type.materialtext
local.embargo.terms2022-08-06
thesis.degree.departmentVeterinary Biomedical Sciences
thesis.degree.disciplineVeterinary Biomedical Sciences
thesis.degree.grantorUniversity of Saskatchewan
thesis.degree.levelDoctoral
thesis.degree.nameDoctor of Philosophy (Ph.D.)

Files

Original bundle
Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
RAMESH-DISSERTATION-2019.pdf
Size:
224.64 MB
Format:
Adobe Portable Document Format
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
LICENSE.txt
Size:
2.27 KB
Format:
Plain Text
Description: