Mulberry leaf multi-components exert hypoglycemic effects through regulation of the PI-3K/Akt insulin signaling pathway in type 2 diabetic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Phytochemicals have unique advantages in the treatment of diabetes due to their multi-target activity and low toxicity. Mulberry leaves, a traditional Chinese herbal medicine, have been used in the prevention and treatment of diabetes for centuries. The main active ingredients in mulberry leaves with regards to the hypoglycemic effect are 1-deoxynojirimycin, flavonoids, and polysaccharides. However, the combined hypoglycemic effects and mechanisms of mulberry leaf multi-components remain unclear. AIM OF THE STUDY: This study explored the anti-diabetic effects of mulberry leaf multi-components (MMC) and the role of the PI-3K/Akt insulin signalling pathway in improving insulin resistance. MATERIALS AND METHODS: The main chemical components of MMC were analyzed using the phenol-sulfuric acid method, aluminum nitrate-sodium nitrite method, and HPLC-ultraviolet/fluorescence detection method. The T2DM rat model was created via feeding a high-fat diet and peritoneal injection of streptozotocin. T2DM rats were divided into four groups: model, model plus metformin, model plus low-dose, and model plus high-dose MMC groups (100 and 200 mg/kg body weight/day, respectively), and plus normal group for a total of five groups. MMC was administered by oral gavage for six weeks. Fasting blood glucose and serum lipid profiles were measured using a glucometer and an automatic biochemistry analyzer, respectively. Serum insulin and adipocytokine levels were analyzed by ELISA. Hepatic glucose metabolizing enzyme activity was evaluated by ELISA and the double antibody sandwich method. Expression of PI-3K/Akt signalling pathway proteins was analyzed by RT-PCR and Western blotting. RESULTS: Extracted 1-deoxynojirimycin, flavonoid, and polysaccharide purity was 70.40%, 52.34%, and 32.60%, respectively. These components were then mixed at a ratio of 1:6:8 to form MMC. MMC significantly reduced serum glucose, insulin, and lipid levels. In diabetic rats, MMC enhanced insulin sensitivity and alleviated inflammatory and oxidative damage by lowing adipocytokine levels and increasing anti-oxidative enzyme activity. Insulin resistance was also mitigated. MMC regulated the activity of key downstream enzymes of hepatic glucose metabolism via activating the expression of PI-3K, Akt, PDX-1, and GLUT4 at the mRNA and protein levels, thereby correcting hepatic glucolipid metabolism disorders and exerting a hypoglycemic effect. CONCLUSION: MMC ameliorated hepatic glucolipid metabolism disorders and improved insulin resistance in T2DM rats by activating the PI-3K/Akt signaling pathway. These results highlight the multi-component, multi-target, and combined effects of MMC, and suggest it may be further developed as a hypoglycemic drug.

Sex differences in the non-linear association between BMI and LDL cholesterol in type 2 diabetes.

Background: A data-based study reported the linear relationship between body mass index (BMI) and low-density lipoprotein cholesterol (LDL-C) in a normal population. However, there were no studies giving the suggestion for diabetes patients limited by sample size. This study aimed to investigate the non-linear dose-response relationship between BMI and LDL-C in type 2 diabetes mellitus (T2DM). Method: The study participants registered at the National Metabolic Management Center (MMC) of Beijing Luhe hospital from June 2017 to June 2021. T2DM was diagnosed according to the 1999 World Organization criteria. The generalized additive models (GAMs) were used to investigate the non-linear association between BMI and LDL-C. The relationship between BMI and LDL-C was visualized via the smooth splines function plot by sex. Segmented regressions were fitted to calculate the slopes with different estimated breakpoints. Results: After data cleaning, a total of 2500 participants with T2DM aged 30 to 70 years were included in this study. Compared with females, the spline between BMI and LDL-C showed an Inverted U shape in males. In males, the slopes below and above the breakpoint (26.08. 95% CI: 24.13 to 28.03) were 2.38 (95%CI: 1.06, 3.70) and -0.36 (95%CI: -1.20, 0.48), respectively. Conclusion: There was an Inverted U shape association between BMI and LDL-C in male participants with T2DM, for which the LDL-C was increased with BMI in the lean population, while LDL-C gradually tended to be flat or even decreased in the obese population. However, the Inverted U-shape between BMI and LDL-C was not found in female patients with T2DM.

Analysis on influencing factors of abnormal renal function in elderly patients with type 2 diabetes mellitus.

BACKGROUND: To investigate the related influencing factors of abnormal renal function in elderly in patients with type 2 diabetes mellitus (T2DM) and their clinical significance. METHODS: The clinical data of elderly T2DM patients hospitalized in Beijing Luhe Hospital from January 2013 to June 2016 were retrospectively analyzed. According to their glomerular filtration rate (GFR) levels, these patients were divided into GFR≥90 mL/min/1.73 m2 group (group A), GFR =60-90 mL/min/1.73 m2 group (group B), and GFR <60 mL/min/1.73 m2 group (group C, i.e., abnormal renal function group). Clinical and laboratory indicators were compared among each group. RESULTS: A total of 614 elderly T2DM patients were collected and divided into group A (N.=186), group B (N.=280) and group C (N.=148, 24.10%). Among them, patients clinically diagnosed with diabetic nephropathy (DN) accounted for 13.68%, and those complicated with high blood pressure (HBP) accounted for 61.40%. In Group C, DN accounted for only 29.73%. In elderly T2DM patients, HBP course, systolic blood pressure (SBP), diastolic blood pressure (DBP), 2h postprandial blood glucose (2hPBG), serum total cholesterol (TC) and blood uric acid (BUA) were independent influencing factors associated with abnormal renal function, among which HBP had a more significant impact on abnormal renal function. With the increase of blood pressure (BP) level, the extension in the course of DM, the increase in urinary albumin/creatinine (Alb/Cr) and the decrease in GFR, the incidence rate of abnormal renal function was increased. CONCLUSIONS: HBP course, SBP, DBP, 2hPBG, TC and BUA are independent risk factors for abnormal renal function in elderly patients with T2DM. Well-controlled BP and blood glucose are protective factors, and a comprehensive treatment targeting to the above influencing factors has important clinical significance in preventing and delaying the occurrence and development of abnormal renal function.

ANN model for predicting acrylonitrile wastewater degradation in supercritical water oxidation.

The discharged acrylonitrile wastewater had aroused more and more attention due to the increasingly serious water pollution. Supercritical water oxidation (SCWO) was an effective and fast way to degrade it completely without secondary pollution. To better illustrate the performances of SCWO of acrylonitrile wastewater, the experimental research covered the effects of different operation conditions on TOC reduction, such as reduced temperature (T/Tc), reduced pressure (P/Pc), initial total organic carbon concentration (TOC0), stoichiometric ratio (SR) and residence time (t). For a more accurate prediction of the emissions, two kinds of artificial neural network (ANN) models were adopt to simulate the TOC reductions in the processes of SCWO of acrylonitrile wastewater, including the Cascade-forward back propagation neural network (CFBPNN) and Feed-forward back propagation neural network (FFBPNN). The input parameters of ANN models were T/Tc, P/Pc, TOC0, SR and t. The output parameter was TOC reduction (η). The mean square error (E2) and the coefficient of determination (R2) were used to evaluate the model performances, respectively. Both the model and the experiment results had shown the TOC reduction could be greatly improved by reduced temperature, reduced pressure, initial TOC concentration, stoichiometric ratio and residence time. The FFBPNN model with the hidden neurons numbers of 12 was shown much better performances than the CFBPNN model.

A B3LYP and MP2(full) theoretical investigation into cooperativity effects, aromaticity and thermodynamic properties in the Na(+)⋯benzonitrile⋯H2O ternary complex.

The cooperativity effects between H-bonding and Na(+)⋯π or Na(+)⋯σ interactions in Na(+)⋯benzonitrile⋯H2O complexes were investigated using the B3LYP and MP2(full) methods with 6-311++G(2d,p) and aug-cc-pVTZ basis sets. The thermodynamic cooperativity and the influence of this cooperativity on aromaticity was evaluated by nucleus-independent chemical shifts (NICS). The results showed that the influence of the Na(+)⋯σ or Na(+)⋯π interaction on the hydrogen bond is more pronounced than that of the latter on the former. The cooperativity effect appeared in the Na(+)⋯σ interaction complex while the anti-cooperativity effect tended to be in the Na(+)⋯π system. The change in enthalpy is the major factor driving cooperativity. Thermodynamic cooperativity is not in accordance with the cooperativity effect evaluated by the change of interaction energy. The ring aromaticity of is weakened while the bond dissociation energy (BDE) of the C-CN bond increases upon ternary complex formation. The cooperativity effect (E coop) correlates with R c (NICS(1)ternary/NICS(1)binary) and ΔΔδ (Δδ ternary - Δδ binary) involving the ring and C ≡ N bond, as well as R BDE(C-CN) [BDE(C-CN)ternary/BDE(C-CN)binary], respectively. AIM (atoms in molecules) analysis confirms the existence of cooperativity.