Vildagliptin, a DPP4 inhibitor, alleviates diabetes-associated cognitive deficits by decreasing the levels of apoptosis-related proteins in the rat hippocampus.

Cognitive impairment is a prevalent but underestimated complication of diabetes, which can cause spatial memory and learning deficits. In the present study, a streptozotocin-induced type 2 diabetic rat model was employed to investigate the effects of vildagliptin, a new oral hypoglycemic agent that acts by inhibiting dipeptidyl peptidase-4, on diabetes-associated cognitive impairments, as well as the molecular mechanisms involved. The present findings demonstrated that vildagliptin treatment prevented memory impairment and decreased the apoptosis of hippocampal neurons. It also attenuated the abnormal expression of caspase-3, B cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein in the diabetic model. Vildagliptin treatment also reversed diabetes-induced decreases in phosphorylated (p)-protein kinase B (Akt) and p-glycogen synthase kinase 3ß (GSK3ß), brain-derived neurotrophic factor and nerve growth factor expression levels. The results indicated that the administration of vildagliptin exerts a protective effect against cognitive deficits by decreasing the expression of apoptosis-related proteins in the hippocampus and that this protective effect was mediated via the Akt/GSK3ß signaling pathway.

Inhibition of microRNA-9-3p reduces lipid accumulation in HepG2 cells by targeting the expression of sirtuin type 1.

Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder caused by the interaction of environmental factors and multiple genes. The genetic background of T2DM is complex and remains to be fully elucidated. MicroRNAs (miRNAs) are negative regulators of gene expression and several miRNAs are associated with the development of T2DM. However, the expression and biological function of miRNA­9­3p in lipid metabolism of patients with T2DM remain to be fully elucidated. The predominant aim of the present study was to examine the effect of miRNA­9­3p on lipid accumulation in HepG2 cells. To investigate this, an MTT assay was used to determine cell proliferation, and the effects of miRNA­9­3p on triglycerides (TG) and total cholesterol (TC) in the HepG2 cells were also examined. Reverse transcription­quantitative polymerase chain reaction and western blot analyses were used to measure the expression levels of SIRT1 at the gene and protein levels, respectively. The date revealed that downregulation of miRNA­9­3p inhibited the proliferation of HepG2 cells, and significantly reduced the accumulation of lipids, and decreased TG and TC content. In addition, the present study demonstrated that inhibition of miRNA­9­3p increased the protein expression of sirtuin type 1 (SIRT1), but had no effects on the gene expression of SIRT1. Therefore, these findings demonstrated that the inhibition of miRNA­9­3p reduced the proliferation of HepG2 cells and lipid accumulation by upregulating the expression of SIRT1, indicating its potential as a therapeutic target.

9p21 polymorphisms increase the risk of peripheral artery disease in the Han Chinese population.

OBJECTIVE: A case-control study to investigate the association of the 9p21 single nucleotide polymorphisms (SNPs) rs10757274 and rs10757278 (known to be associated with coronary artery disease [CAD] risk) with peripheral arterial disease (PAD), in a Han Chinese population. METHODS: The rs10757274 and rs10757278 genotypes of patients with PAD, and age- and sex-matched control subjects, were determined. Multivariate unconditional logistic regression analyses were performed, with adjustments for age, sex, hypertension, dyslipidaemia, diabetes and smoking status. RESULTS: The study included 420 patients with PAD and 418 control subjects. Variant forms of both SNPs were associated with increased risk of PAD in the total study population, when excluding patients with CAD or stroke (additive genetic model). The GG haplotype increased the risk of PAD, but this association did not remain significant after further sensitivity analysis. Both SNPs were associated with PAD risk in patients aged <65 years, but not in those aged ≥ 65 years (additive model). CONCLUSIONS: 9p21 is associated with PAD. When stratified according to age, 9p21 increases PAD risk in individuals aged <65 years, but not in those aged ≥ 65 years.

Low BDNF is associated with cognitive deficits in patients with type 2 diabetes.

OBJECTIVE: Studies suggest that brain-derived neurotrophic factor (BDNF) plays an essential role in regulating memory-related neuroplasticity in the hippocampus. Type 2 diabetes (T2DM) is associated with impairment in many domains of cognitive function which may result from reduced BDNF; however, the correlation of BDNF with cognitive impairment in T2DM has not been investigated. MATERIALS AND METHODS: We compared 208 patients with T2DM to 212 normal controls on serum BDNF and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). RESULTS: Serum BDNF levels were significantly decreased in T2DM patients compared to normal controls (p < 0.001). The total score and nearly all indexes (all p < 0.01) except for attention and visuospatial/constructional indexes (all p > 0.05) of RBANS were markedly lower in T2DM than controls. There was a positive relationship between serum BDNF and delayed memory in patients with T2DM. CONCLUSION: Our results suggest that BDNF may play a role in the pathophysiology of cognitive deficits, especially delayed memory in T2DM.