The functional role of cardiac non-neuronal cholinergic system in the diabetic heart
Saw, Eng Leng
Cite this item:
Saw, E. L. (2020). The functional role of cardiac non-neuronal cholinergic system in the diabetic heart (Thesis, Doctor of Philosophy). University of Otago. Retrieved from http://hdl.handle.net/10523/9912
Permanent link to OUR Archive version:
http://hdl.handle.net/10523/9912
Abstract:
In type-2 diabetes mellitus (T2DM), insulin resistance and metabolic derangements reduce glucose transporter-4 (GLUT-4) expression to decrease glucose uptake, and hence the glucose oxidation in the diabetic heart. Further, the diabetic heart displays reduced basal myocardial energy status while diminished glucose oxidation further aggravates this condition in myocardial ischemia. Previous studies showed that normalization of glucose metabolism via increasing GLUT-4 expression attenuated diabetes-induced cardiac dysfunction. Cardiomyocytes possess a non-neuronal cholinergic system (NNCS) that consists of choline acetyltransferase (ChAT), choline transporter 1 (CHT1), vesicular acetylcholine transporter (VAChT), and acetylcholinesterase (AChE) to synthesize, release and degrade acetylcholine (ACh), respectively. The released ACh binds to type-2 muscarinic ACh receptor (M2AChR) and mediates pro-survival phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) /hypoxia-inducible factor1α (HIF1α) signaling cascade to promote glucose metabolism through increasing GLUT-4 expression in normoxic condition. However, the expression and function of cardiac NNCS are not known in the diabetic heart. Therefore, the main aim of this thesis was to examine the role of cardiac NNCS in the diabetic heart.
Date:
2020
Advisor:
Katare, Rajesh; Fronius, Martin
Degree Name:
Doctor of Philosophy
Degree Discipline:
Physiology
Publisher:
University of Otago
Keywords:
diabetes; cardiovascular; nncs
Research Type:
Thesis
Languages:
English
Collections
- Thesis - Doctoral [3042]
- Physiology [154]