SLC35b4, solute receptor for UDP-N-acetylglucosamine and UDP-xylose, is associated with diabetes and predisposing conditions. This study investigated the localization of SLC35b4 and its role in the regulation of protein expression, and compared the differential expression between a knockdown of SLC35b4 and controls in HepG2. Responsiveness to glucose, expression and localization were assayed using western blot and immunostaining. Localization was confirmed using PLA. 2D gel electrophoresis and MALDI-TOF were used to identify differentially expressed proteins and pathway analysis was performed. SLC35b4 was increased by 60% upon glucose stimulation and localized in Golgi apparatus and endoplasmic reticulum. Presence of SLC35b4 in the Golgi apparatus confirms its involvement in the biosynthesis of glycoconjugate proteins. Four proteins were markedly under-expressed (Hsp60, HspA8, TUBA1A, and ENO1), and were linked to the pathogenesis of diabetes or were post-translationally modified by O-GlcNAc. Glucose levels may activate SLC35b4 expression and localization to the ER and Golgi apparatus. This triggers a downstream effect via Hsp60 and other proteins, potentially via altering the glycosylation pattern inside liver cells. The downstream cascade alters the ability of cultured liver cells to inhibit endogenous glucose production, and plays a role in the association of the above listed genes with the pathogenesis of diabetes.

Protein profiling reveal SLC35b4 responds to glucose stimulation and acts through modulating molecular Hsp60