Soha N Yazbek
American University of Beirut, Lebanon
Scientific Tracks Abstracts: J Diabetes Metab
Type II diabetes is one of the most common endocrine disorders. The cumulative action of genetic variants account for 10% of heritability. SLC35b4, a solute receptor associated with obesity, insulin resistance and gluconeogenesis, transports UDP-Nacetylglucosamine and UDP-Xylose. The correlation between expression and functionality and the mechanism of action have not been elucidated. This study aimed to investigate the regulation of protein expression and localization of SLC35b4. We also aimed at comparing differentially expressed proteins between a knockdown of SLC35b4 and controls in HepG2 cells in order to decode its implication in macromolecules glycosylation and sugar production. Responsiveness was assayed using western blot analysis and immunostaining. To identify the cytoplasmic compartment harboring SLC35b4, double immunofluorescence (SLC35b4-Golgi apparatus and endoplasmic reticulum) studies were performed. The subcellular localization was confirmed using a PLA technique (duo-link). 2D gel elctrophoresis and MALDI_TOF were used to identify differentialy expressed protiens. Pathway analysis was performed to understand the downstream effect of the gene knock-out. Results revealed SLC35b4 is increased up to 60% upon glucose stimulation. SLC35b4 localized with Golgi apparatus and to a lesser extent with the endoplasmic reticulum. The presence of SLC35b4 in the Golgi apparatus confirms its involvement in the biosynthesis of glycoconjugates proteins. Four proteins were under-expressed when SLC35b4 gene was knocked out (HSPD, HSPA8, TUBA1A, and ENO1), all of which are involved in pathways affecting glucose and insulin homeostasis.We suggest that SLC35b4 activation alters the glycosylation pattern inside the cells causing an improvement of the insulin ability to inhibit endogenous glucose production.
Soha N Yazbek is an Assistant Professor of Genetics at the Medical Laboratory Sciences Program, AUB. She is trained in Basic Genetics and focuses on researching the genetic basis of complex multifactorial diseases (diabetes and non-communicable diseases). She also works to identify the research gap in non-communicable diseases in selected countries of the region. Recently, her research has focused on the genetic disease status and the genetic service response in Lebanon. She holds a PhD in Genetics from Case Western Reserve University, and MS in Molecular Biology from the Lebanese American University and a BS in Medical Laboratory Sciences at AUB.
Email: sy21@aub.edu.lb
