The disorders of glucolipid metabolism are prevalent in patients with type 2 diabetes
mellitus (T2DM). Since the effects of Palmitic-Acid-Hydroxy-Stearic Acid (PAHSA)
on T2DM were not fully understood, the study aimed to investigate the role of S-9-
PAHSA in diabetes and the possible mechanisms. Male C57BL6 mice were fed with a
high-fat diet (HFD) and injected with streptozotocin (STZ) to establish the diabetic
mice model, and then administered with low- or high-dose S-9-PAHSA. Insulin,
glycosylated serum protein (GSP), glucagon-like peptide-1 (GLP-1), and oxidized lowdensity
lipoprotein (ox-LDL) were assessed by ELISA. SH-SY 5Y cells were incubated
in a diabetic environment and treated with S-9-PAHSA, R-9-PAHSA, or 9-PAHSA.
Cell viability, cell proliferation, apoptosis, lactate dehydrogenase (LDH), and reactive
oxygen species (ROS) were measured by corresponding kits. Protein expressions were
determined by western blot. The results showed high-does S-9-PAHSA improved
insulin resistance and lowered ox-LDL. Compared with the control group, the
significantly up-regulated expression of p62 and down-regulated expression of beclin
1 were found in diabetic mice and could be reversed by S-9-PAHSA. In vitro, S-9-
PAHSA increased cell viability and proliferation while reducing LDH and ROS. S-9-
PAHSA could reduce the expression of cleaved caspase-3 and TUNEL-positive cells,
and increase the ratio of LC3II/I after high glucose and fatty acid stimulation in vitro.
Downward trends were observed in PI3K and the phosphorylation of AKT in diabetic
environments, which could be slightly restored by S-9-PAHSA. In conclusion, S-9-
PAHSA could regulate glycolipid metabolism both in vivo and in vitro, indicating the
vital role of S-9-PAHSA in T2DM.