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Objective@#To investigate the effect of metformin on the expressions of activating transcription factor-6(ATF6)and Caspase12 in hippocampus of type 2 diabetic rats.@*Methods@#GK male rats with random blood glucose≥11.1 mmol/L were orally administrated with normal saline(DM group)and metformin(MET group, 85 mg·kg-1·d-1)for 8 weeks(n=10 each group). Wistar male rats were selected as normal contorl group(NC, n=10). After 8 weeks of continuous medication, body weight and fasting plasma glucose(FPG)were measured, and the morphology of HE stained cells and the expressions of ATF6 and Caspase12 by immunohistochemistry staining in the CA1 area of hippocampus were detected.@*Results@#Compared with NC group, the body weight of DM and MET groups decreased(P<0.05), but there was no significant difference between DM and MET groups(P>0.05). In comparison with NC group, FPG levels in DM and MET groups were markedly increased(P<0.05)while FPG level in MET group was significantly lower than that in DM group(P<0.05). The normal nerve cells in the CA1 region of hippocampal were lower in DM and MET groups than those in NC group, especially in DM group. The protein expressions of ATF6 and Caspase12 in DM and MET groups were higher than that in NC group(all P<0.05), and the expressions of the two protein in MET group were significantly decreased as compared with DM group(P<0.05).@*Conclusion@#Metformin reduces the expressions of ATF6 and Caspase12 in hippocampus of type 2 diabetic rats, which may be related to its protective effect on brain. (Chin J Endocrinol Metab, 2018, 34: 594-597)
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Objective To investigate the neuroprotective effect and mechanism of liraglutide on diabetic rats. Methods 24 healthy male SPF Goto-Kakizaki (GK) rats with random blood glucose greater than 11.1 mmol/L were selected as the experimental group, and randomly divided into diabetes mellitus group ( n＝12) and liraglutide group (n＝12). Ten healthy male SPF Wistar rats with the same age and weight as GK rats were selected as normal control group. After adaptively feeded for 2 weeks, the liraglutide group was given liraglutide (400 μg·kg－1·d－1, subcutaneous injection), while the control group and diabetes mellitus group were given the same volume of saline, and continued to be administered for 8 weeks. After 10 weeks, data and biochemical indicators were recorded. Effects of liraglutide on learning and memory in diabetes mellitus rats were detected by Morris water maze test. HE staining observed the hippocampal neurons morphology. Western blotting method detected the expression of p- IκB kinase (IKK) β, p-NF-κB, NF-κB, Klotho, and PRX2 in hippocampus. Results Morris water maze test showed that liraglutide can improve the spatial learning and memory ability of diabetes mellitus rats. HE staining showed that liraglutide significantly reduced the pathological damage of hippocampal neurons of diabetes mellitus rats. Western blotting showed that liraglutide inhibited NF-κB signaling pathway in hippocampus of diabetes mellitus rats. The expression of Klotho protein in hippocampus of diabetes mellitus group was significantly lower than that of control group, while the expression of PRX2 protein was higher than control group (t＝8.298,－7.398,all P<0.01). The expression of Klotho and PRX2 protein in hippocampus of liraglutide group were higher than diabetes mellitus group (t＝－13.059, 14.113, all P<0.01). The expression of Klotho protein of liraglutide group was similar to that of control group ( t ＝ －1. 137, P>0. 05 ). The expression of PRX2 protein was significantly higher than control group (t＝－28.055, P<0.01). Conclusions Liraglutide may enhance the expression of antioxidant stress protein including Klotho and PRX2, by inhibiting NF-κB signaling pathway in hippocampus of diabetes mellitus rats, reduced oxidative stress and improved the injury of hippocampal neuronal in diabetes mellitus rats, which seems to play a neuroprotective effect, to prevent and delay the occurrence of diabetic encephalopathy.
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Objective Decline in cognitive function caused by diabetes has become a research hotpots.The article aims to explore the relationship between serums regulated upon activation normal T cell expressed and secreted(RANTES) and cognitive dysfunction of newly diognosed T2DM patients, and provide a new way of prevention and treatment for newly diagnosed T2DM patients with cognitive dysfunction.Methods We retrospectively analyzed the general information and clinical biochemical indexes of the 123 patients who were first diagnosed of T2DM from March 2015 to September 2016 in Tangshan Worker''s Hospital.The levels of serum RANTES were measured by enzyme-linked immunosorbent assay (ELISA), and the cognitive function of all patients was assessed by Mini-mental State Examinatlon(MMSE)and Repeatable Battery for the Assessment of Neuropsyehologic Status(RBANS).Finally, newly diognosed T2DM patients were divided into T2DM non-cognitive disorder group and T2DM cognitive disorder group according to the MMSE score.We analyzed whether there are differences among general information,serum RANTES level and RBANS cognitive function score of two group patients.The correlations of RANTES with general information and cognitive scores were analyzed by single factor correlation and multiple stepwise regression analysis.Results ①The level of serum RANTESin T2DM cognitive disorder group[(2.62±0.37)mmol/L] was significantly higher compared to that in T2DM noncognitive disorder group[(2.29±0.36)mmol/L], and there was significant difference(P<0.001).②The instant memory,visual span,attention,delayed memory score and RBANS score of T2DM cognitive disorder group were(70.90±14.71)、(92.90±15.50)、(87.80±16.45)、(88.02±14.28)、(82.92±11.07), which were significant declined compared to those of T2DM non-cognitive disorder group [(85.28±13.97),(104.18±12.69),(101.51±12.94),(96.42±10.30),(95.84±9.94)], and there was significant difference (P≤0.05).There was no statistically significant difference between the two groups′ verbal function score [(96.08±7.87),(99.31±9.83)] (P=0.056).③The RANTES was negatively correlated with the total score of instant memory, visual span, verbal function, delayed memory score and RBANS score in T2DM patients(the valuue of r were-3.48、-2.35、-2.01、-3.02、-4.17).Conclusion There was a significant correlation between serum RANTES level and cognitive dysfunction, and elevated serum RANTES level could be used as an important indicator for monitoring newly diognosed T2DM patients with cognitive dysfunction.