ABSTRACT
This study was designed to investigate the therapeutic effect of novel compound Z-9-octadecenyl-2-propanesulfonamide (N15) on diabetes-associated cognitive decline (DACD). Type 2 diabetes (T2DM) mice models were established with multiple injection of low doses of streptozotocin (STZ) in mice on high fat diet (HFD). Vehicle and different concentrations of N15 (50 and 100 mg·kg-1·d-1) were administrated orally for 6 weeks. The step-down test, dark avoidance task and Morris water maze were conducted at the 6th week. The level of glucose and lactic acid in hippocampus were determined and mRNA of growth associated protein-43 (GAP-43), synaptophysin (SYN), brain derived neurotrophic factor (BDNF) and neurotrophins-3 (NT-3) in hippocampus were analyzed by real time PCR. The beneficial effects of N15 on learning and memory were found in the test of step-down, dark avoidance and Morris water maze. N15 reduced the level of glucose and lactic acid in hippocampus of HFD+STZ-induced diabetic encephalopathy model mice. Additionally, the mRNA expression of GAP-43, SYN, BDNF and NT-3 in hippocampus of HFD+STZ-induced diabetic encephalopathy mice were significantly increased by N15 (P<0.01). These results suggest that the novel compound N15 can ameliorate diabetes-associated cognitive decline and the potential mechanism may be associated with the expressions of increased synaptic-related factors and neurotrophic factor in the hippocampus of diabetesassociated cognitive decline in mice.
ABSTRACT
This study was designed to investigate the therapeutic effect and mechanisms of action of novel compound N-(Z)-9-octadecenyl-2-propanesulfonamide (N15) on type 2 diabetes (T2DM). A mouse model of T2DM was established with multiple injection of streptozotocin (STZ) at a low dose. N15 at different doses (50, 100 and 200 mg·kg-1·d-1) and pioglitazone (6 mg·kg-1·d-1) were administrated orally for 6 weeks. The level of fasting blood glucose (FBG) and fasting insulin (FIns) were measured in the course of the experiment for insulin resistance index (HOMA-IR). Oral glucose tolerance test (OGTT) and intraperitoneal insulin tolerance test (IPITT) were determined in the treated mice. The expression of Akt, AMPK and Glut4 in liver were analyzed by Western blot. N15 was found to reduce the level of FBG, FIns and HOMA-IR (P P P P P > 0.05). These results suggested that the novel compound N15 can ameliorate insulin resistance and the potential mechanism may be associated with increased insulin signaling in liver and promotion of phosphatidyl inositol 3 phosphate phosphorylation.