Pancreatic β-cell dysfunction resulting from inflammation has been recognized to contribute to type 2 diabetes mellitus (T2DM). Netrin-1 is a new indicator of subclinical inflammation and it has a role in β-cell apoptosis. This study evaluated the level of netrin-1 in newly diagnosed T2DM patients and explored whether netrin-1 is a reliable marker or a key factor in the development of T2DM. Netrin-1 level was determined using a commercially available human enzyme-linked immune sorbent assay (ELISA) kit. The homeostasis model assessment of insulin resistance (HOMA-IR) was used as an index to measure insulin resistance. The sample consisted of 30 patients with newly diagnosed T2DM who had a glycosylated hemoglobin (HbA1c) level ranging from 7.5 % (58 mmol/mol) to 10.5 % (91 mmol/mol). The control group consisted of 26 healthy individuals matched for age and body mass index. The netrin-1 level of T2DM patients was significantly lower than that of healthy controls (p < 0.01). Logistic regression analysis showed that the level of netrin-1 was negatively correlated with HOMA-IR, fasting blood glucose, postprandial blood glucose, fasting insulin and HbA1c. Plasma netrin-1 levels were decreased in patients with newly diagnosed T2DM, and the levels of netrin-1 were negatively associated with IR and glucose homeostasis. Future studies on the precise mechanism will offer new insights into the prevention and treatment of T2DM.

Transplantation of bone marrow mesenchymal stem cells (BMSCs) has been developed as a new method of treating diseases of the peripheral nervous system. While netrin-1 is a critical molecule for axonal path finding and nerve growth, it may also affect vascular network formation. Here, we investigated the effect of transplanting BMSCs that produce netrin-1 in a rat model of sciatic nerve crush injury. We introduced a sciatic nerve crush injury, and then injected 1×10(6) BMSCs infected by a recombinant adenovirus expressing netrin-1 Ad5-Netrin-1-EGFP or culture medium into the injured part in the next day. At day 7, 14 and 28 after injection, we measured motor nerve conduction and detected mRNA expressions of netrin-1 receptors UNC5B and Deleted in Colorectal Cancer (DCC), and neurotrophic factors brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) by real-time PCR. We also detected protein expressions of BDNF and NGF by Western blotting assays and examined BMSCs that incorporated into myelin and vascellum. The results showed that BMSCs infected by Ad5-Netrin-1-EGFP significantly improved the function of the sciatic nerve, and led to increased expression of BDNF and NGF (P<0.05). Moreover, 28 days after injury, more Schwann cells were found in BMSCs infected by Ad5-Netrin-1-EGFP compared to control BMSCs. In conclusion, transplantation of BMSCs that produce netrin-1 improved the function of the sciatic nerve after injury. This method may be a new treatment of nerve injury.

Aims: Our study was designed to explore the applied characteristics of the back propagation artificial neural network (BPANN) on studying the genetic variants in adipnectin ADIPOQ, peroxisome proliferator-activated receptor (PPAR)-γ, and retinoid X receptor-α (RXR-α) genes and type 2 diabetes mellitus (T2DM) risks in a Chinese Han population. Subjects and Methods: We used BPANN as the fitting model based on data gathered from T2DM patients (n=913) and normal controls (n=1,001). The mean impact value (MIV) for each input variables were calculated, and the sequence of the factors according to their absolute MIVs was sorted. Results: The results from BPANN were compared with multiple logistic regression analysis, and the generalized multifactor dimensionality reduction (GMDR) method was used to calculate the joint effects of ADIPOQ, PPAR-γ, and RXR-α genes. By BPANN analysis, the sequence according to the importance of the T2DM risk factors was in the order of serum adiponectin level, rs3856806, rs7649121, hypertension, rs3821799, rs17827276, rs12495941, rs4240711, age, rs16861194, waist circumference, rs2241767, rs2920502, rs1063539, alcohol drinking, smoking, hyperlipoproteinemia, gender, rs3132291, T2DM family history, rs4842194, rs822394, rs1801282, rs1045570, rs16861205, rs6537944, body mass index, rs266729, and rs1801282. However, compared with multiple logistic regression analysis, only 11 factors were statistically significant. After overweight and obesity were taken as environment adjustment factors into the analysis, model A2 B4 C5 C6 C8 (rs3856806, rs4240711, rs7649121, rs3821799, rs12495941) was the best model (coefficient of variation consistency=10/10, P=0.0107) in the GMDR method. Conclusions: These results suggested the interactions of ADIPOQ, PPAR-γ, and RXR-α genes might play a role in susceptibility to T2DM. BPANN could be used to analyze the risk factors of diseases and provide more complicated relationships between inputs and outputs.

Background: Asprosin, a novel adipokine that raises glucose levels and stimulates appetite, has been proved to be pathologically increased in populations predisposed to type 2 diabetes mellitus (T2DM), obesity, and cardiovascular diseases. The mechanisms of sodium-glucose co-transporter-2 (SGLT2) inhibitors for hypoglycemic effect and cardiovascular protection have not been fully clarified. Therefore, we conducted this study to assess change in the levels of serum asprosin after treatment with SGLT2 inhibitors in patients with newly diagnosed T2DM. Methods: This study was a randomized, double-blind, placebo-controlled trial. A total of 29 participants with newly diagnosed T2DM with body mass index (BMI) ≥ 23.0 kg/m² and haemoglobin A1c (HbA1c) levels of 58–85 mmol/mol (7.5–10%) were randomized to SGLT2 inhibitors dapagliflozin 10 mg/d (n = 19) or placebo (n = 10) treatment for 24 weeks. We analyzed asprosin concentrations by an enzyme-linked immunosorbent assay. Besides, body weight, BMI, HbA1c, fasting plasma glucose (FPG), and lipid levels were measured at baseline and 24 weeks. Results: At 24 weeks, participants with SGLT2 inhibitors treatment exhibited lower levels of serum asprosin (22.87 vs 45.06 ng/ml in the placebo group; P < 0.001) after adjusting for baseline values. The levels of body weight, BMI, HbA1c, FPG, and triglyceride (TG) were decreased, while high density lipoprotein-cholesterol (HDL-C) was increased after SGLT2 inhibitors dapagliflozin treatment compared with placebo (P < 0.05 for all). Low density lipoprotein-cholesterol (LDL-C) and total cholesterol (TC) levels were unchanged in the SGLT2 inhibitors group and placebo group. No statistical correlation was found between the levels of serum asprosin and body weight, BMI, HbA1c, FPG, and lipid levels during the SGLT2 inhibitor dapagliflozin treatment. Conclusions: These findings indicated that SGLT2 inhibitors can lower serum asprosin levels and improve glucolipid and weight in patients with newly diagnosed T2DM, which may benefit the cardiovascular system. Trial registration CTR20131268; Registered 20 March 2014 CTR20150102; Registered 03 March 2015. http://www.chinadrugtrials.org.cn/clinicaltrials.searchlistdetail.dhtml.