GLP-2 ameliorates D-galactose induced muscle aging by IGF-1/Pi3k/Akt/FoxO3a signaling pathway in C2C12 cells and mice.

BACKGROUND: The study aimed to investigate the effect of Glucagon-like peptide-2 (GLP-2) on muscle aging in vivo and in vitro. METHODS: Six-week-old C57BL/6J mice were administered with D-galactose (200 mg/kg/day, intraperitoneally) for 8weeks, followed by daily subcutaneous injections of GLP-2 (300 or 600 µg/kg/day) for 4weeks. Skeletal muscle function and mass were evaluated using relative grip strength and muscle weight. The sizes and types of muscle fibers and apoptosis were assessed through histological analysis, immunofluorescence staining, and TUNEL staining, respectively. C2C12 myotubes were treated with D-galactose (40 mg/mL) and GLP-2. Protein expression of differentiation-related myogenic differentiation factor D (MyoD), myogenin (MyoG), and myosin heavy chain (Myhc), degradation-related Muscle RING finger 1 (MuRF-1), and muscle atrophy F-box (MAFbx)/Atrogin-1, and apoptosis-related B-cell leukemia/lymphoma 2 (Bcl-2) and Bax, were assessed using western blots. The Pi3k inhibitor LY294002 was applied to investigate whether GLP-2 regulated myogenesis and myotube aging via IGF-1/Pi3k/Akt/FoxO3a signaling pathway. RESULTS: The results demonstrated that GLP-2 significantly reversed the decline in muscles weight, relative grip strength, diameter, and cross-sectional area of muscle fibers induced by D-galactose in mice. Apart from suppressing the expressions of MuRF-1 and Atrogin-1 in the muscles and C2C12 myotubes, GLP-2 significantly increased the expressions of MyoD, MyoG, and Myhc compared to the D-galactose. GLP-2 significantly suppressed cell apoptosis. Western blot analysis indicated that the regulation of GLP-2 may be attributed to the activation of theIGF-1/Pi3k/Akt/FoxO3a phosphorylation pathway. CONCLUSIONS: This study suggested that GLP-2 ameliorated D-galactose induced muscle aging by IGF-1/Pi3k/Akt/FoxO3a pathway.

Association between renal function and bone mineral density in patients with type 2 diabetes mellitus.

Background: This study evaluated the association between renal function, assessed by serum creatinine and estimated glomerular filtration rate (eGFR) according to the Cockcroft-Gault (CG) and Modification of Diet in Renal Disease (MDRD) equations, and bone mineral density (BMD) in Chinese patients with type 2 diabetes mellitus (T2DM). Methods: 1322 patients with T2DM were included, and their basic clinical information, serum biochemical tests, and BMD at the total hip and femur neck were collected. Multivariate adjusted linear regression, smooth curve fitting and a piecewise linear regression model were used to analyze linear and nonlinear associations. Age, BMI, drinking, smoking, systolic blood pressure and diastolic blood pressure, FBG, HbA1C, course of diabetes, hsCRP, TC, TG, HDL-C, LDL-C, Ca, P, PTH, ALP, OC, P1NP, ß-CTX and 25(OH)D were adjusted. Results: After adjusting the variables, no correlation between eGFR CG and eGFR MDRD and femur neck BMD was observed in women, men, or the total population. The eGFR CG and eGFR MDRD had a significant positive association with total hip BMD in men and the total population with T2DM. With a 10-unit decrease in eGFR CG, total hip BMD reduced by 0.012 g/cm2 in men and 0.010 g/cm2 the total population. Total hip BMD reduced by 0.014 g/cm2 in men and 0.022 g/cm2 in the total population with a 10-unit decrease in eGFR MDRD. There was no correlation between eGFR CG or eGFR MDRD and total hip BMD in female participants. Conclusion: Impaired renal function was associated with decreased total hip BMD in men and the total population with T2DM. No associated between renal function with femur neck BMD was observed.

Insight into the comprehensive effect of carbon dioxide, light intensity and glucose on heterotrophic-assisted phototrophic microalgae biofilm growth: A multifactorial kinetic model.

Heterotrophic-assisted photoautotrophic microalgae biofilm cultivation was an alternative way to realize CO2 reduction and wastewater treatment. Growth kinetics supplied a channel to better understand how the cultivation conditions affect microalgal growth and CO2 reduction. However, the two growth modes (heterotroph and photoautotroph) have different needs for organic and inorganic nutrients. Thus, combining the threshold theory and multiplication theory, an integral multifactorial kinetic model that looking insight into the comprehensive effect of glucose, CO2, light intensity, and nitrate was developed for heterotrophic-assisted photoautotrophic microalgae biofilm growth in this study. R2 between model and experiment was 0.99. It predicted the maximum specific growth rate and maximum CO2 consumption rate of heterotrophic-assisted photoautotrophic microalgae biofilm was 1.868 h-1 and 1.02 h-1, respectively. This model fully explained the influence of the main factors on microalgae biofilm growth and reasonably predicted the growth rate of microalgae biofilm under different growth conditions.

Association between preoperative lipid profiles and new-onset diabetes after transplantation in Chinese kidney transplant recipients: A retrospective cohort study.

BACKGROUND: This study investigated the association between the preoperative lipid profiles and new-onset diabetes after transplantation (NODAT) in Chinese kidney transplant recipients (KTRs). METHODS: In this study, of 1140 KTRs registered between January 1993 and March 2018 in Zhongshan Hospital, Fudan University, 449 were enrolled. Clinical data, obtained through a chart review of the patient records in the medical record system, were evaluated, and NODAT was diagnosed based on the American Diabetes Association guidelines. Multivariate Cox regression analysis was conducted to determine whether the preoperative lipid profiles in KTRs were independently associated with NODAT incidence. The preoperative lipid profiles were analyzed as continuous variables and grouped into tertiles. Smooth curve fitting was used to confirm the linear associations. RESULTS: During a median follow-up of 28.03 (interquartile range 12.00-84.23) months, 104 of the 449 (23.16%) participants developed NODAT. The multivariate model analysis, adjusted for all potential covariates, showed that increased values of the following parameters were associated with NODAT (hazard ratio, 95% confidence interval): preoperative total cholesterol (TC; 1.25, 1.09-1.58, p = 0.0495), low-density lipoprotein cholesterol (LDL-C; 1.33, 1.02-1.75, p = 0.0352), non-high-density lipoprotein cholesterol (non-HDL-C; 1.41, 1.09-1.82, p = 0.0084), TC/HDL-C (1.28, 1.06-1.54, p = 0.0109), and non-HDL-C/HDL-C (1.26, 1.05-1.52, p = 0.0138). However, the association between the preoperative triglyceride, HDL-C, or TG/HDL-C and NODAT was not significant. CONCLUSIONS: Preoperative TC, LDL-C, non-HDL-C, TC/HDL-C, and non-HDL-C/HDL-C were independent risk factors for NODAT.

Linear and Non-linear Correlations Between Serum Phosphate Level and Bone Mineral Density in Type 2 Diabetes.

Introduction: Serum phosphate plays an important role in bone mineralization and might be a risk factor for many bone diseases. Patients with T2D usually have low serum phosphate level due to diet control, osmotic diuresis, and insulin stimulation. Current studies have discussed the linear association between serum phosphate and bone mineral density (BMD). Objective: We aimed to analyze both the linear and non-linear correlations between serum phosphate and BMD in patients with type 2 diabetes (T2D). Methods: We included 1,469 patients with T2D and obtained their basic information, laboratory measurements, and BMD data. Multivariate adjusted linear regression was used to analyze the linear associations, and we applied a two-piecewise linear regression model using a smoothing function to examine the non-linear association. Results: No linear correlation was found between serum phosphate and BMD in patients with T2D. In women with T2D, we found a non-linear correlation between serum phosphate level and femur neck or total hip BMD. When serum phosphate was <1.3 mmol/L, it was positively associated with femur neck and total hip BMD, whereas when phosphate was >1.3 mmol/L, it was negatively associated with femur neck BMD. Conclusions: In men with T2D, serum phosphate level was not associated with BMD. However, in women with T2D, we found a non-linear correlation between serum phosphate and femur neck or total hip BMD.

Prospect of Sodium-Glucose Co-transporter 2 Inhibitors Combined With Insulin for the Treatment of Type 2 Diabetes.

Sodium-glucose co-transporter 2 (SGLT2) inhibitors are a new family of antidiabetic drugs that reduce blood glucose independent of insulin. In this review, we present the advantages and adverse effects of SGLT2 inhibitors plus insulin therapy as a treatment regimen for patients with type 2 diabetes (T2D). Compared with placebo, SGLT2 inhibitors plus insulin therapy could significantly decrease fasting blood glucose and HbA1c, thereby reducing the daily required dose of insulin. A reduction in body weight and improvements in insulin resistance and ß-cell function have also been widely reported with this therapy, and other potential advantages, including the reduction in blood pressure, adverse cardiovascular outcomes, and visceral adipose tissue volume, have been revealed. SGLT2 inhibitors cause a greater reduction than dipeptidyl peptidase-4 (DPP-4) inhibitors in body weight and the risk of cardiovascular disease. Furthermore, compared with glucagon-like peptide-1 (GLP-1) agonists, SGLT2 inhibitors reduce blood pressure, and heart failure. As this therapy is an oral preparation, an improvement in patient compliance is also achieved. Despite these advantages, however, combination therapy with SGLT2 inhibitors and insulin has several risks. Although no difference has been found in the incidence of hypoglycemic events and urinary tract infection between the administration of this combination and that of placebo, the risk of genital tract infections was reported to increase with the combination therapy. Additionally, bone adverse effects, euglycemic diabetic ketoacidosis, and volume depletion-and osmotic diuresis-related adverse effects have been observed. Altogether, we could conclude that SGLT2 inhibitors plus insulin therapy is an efficient treatment option for patients with T2D, especially those requiring high daily insulin doses and those with insulin resistance, obesity, and a high risk of cardiovascular events. However, careful monitoring of the adverse effects of this combination is also warranted.

Association between serum levels of bone turnover markers and bone mineral density in men and women with type 2 diabetes mellitus.

BACKGROUND: In patients with type 2 diabetes mellitus (T2DM), higher risks of impaired bone metabolism are widely reported. To evaluate bone metabolism, bone mineral density (BMD) and bone turnover levels should be included. In this article, we analyzed the relationship between them in T2DM. METHODS: We conducted a hospital-based cross-sectional study enrolling 1499 patients hospitalized for T2DM between October 2009 and January 2013. Multivariate linear regression models were used to identify the relationship between bone turnover markers (BTMs) and BMD levels. A two-sided P-value < .05 was considered statistically significant. RESULTS: After adjusting for confounding factors, osteocalcin (OC) showed a negative relationship with total lumbar, femur neck, and total hip BMD in men and women. N-terminal propeptides of type I collagen (P1NP) and alkaline phosphatase (ALP) showed a negative association with BMD at three sites in men and total lumbar BMD in women, whereas in the femur neck and total hip in women, the relationship was only found for P1NP with total hip. For ß-C-terminal telopeptides of type I collagen (ß-CTX), a negative relationship was also found in all three sites for BMD in men and total lumbar BMD in women, whereas ß-CTX was not associated in the femoral neck and total hip in women. CONCLUSION: In patients with T2DM, serum levels of OC, P1NP, ß-CTX, and ALP were negatively correlated with BMD levels in men in three sites and with total lumbar BMD in women. The relationship varied in femur neck and total hip BMD in women.

Association Between Bone Mineral Density, Bone Turnover Markers, and Serum Cholesterol Levels in Type 2 Diabetes.

Purpose: The association between bone mineral density (BMD), bone turnover markers, and serum cholesterol in healthy population has already been proved. However, in patients with type 2 diabetes mellitus (T2D), it has not been adequately analyzed. In this study, we investigated the correlation between BMD, bone turnover markers, and serum cholesterol levels in people with T2D. Methods: We enrolled 1,040 men and 735 women with T2D from Zhongshan Hospital between October 2009 and January 2013. Their general condition, history of diseases and medication, serum markers, and BMD data were collected. We used logistic regression analysis to identify the association between serum cholesterol levels and BMD as well as bone turnover markers. Results: In multivariate regression analysis, we observed that in men with T2D, high high-density lipoprotein-cholesterol and total cholesterol levels were significantly associated with low total lumbar, femur neck, and total hip BMD, while low-density lipoprotein-cholesterol level was only inversely associated with total lumbar and femur neck BMD. Total cholesterol and low-density lipoprotein-cholesterol levels were also negatively associated with osteocalcin, procollagen type I N-terminal propeptide, and ß-crosslaps. In women with T2D, high-density lipoprotein-cholesterol level was observed to be negatively correlated with total lumbar, femur neck, and total hip BMD, while total cholesterol and low-density lipoprotein-cholesterol levels were only associated with BMD at the total lumbar. Furthermore, total cholesterol was also negatively associated with osteocalcin, procollagen type I N-terminal propeptide, and ß-crosslaps; high-density lipoprotein-cholesterol was only related to osteocalcin and parathyroid hormone, while low-density lipoprotein-cholesterol was only related to ß-crosslaps in women. Conclusion: Our study suggests a significantly negative correlation between serum cholesterol levels and BMD in both men and women with T2D. The associations between serum cholesterol levels and bone turnover markers were also observed in T2D patients.

Optimizing culture conditions for heterotrophic-assisted photoautotrophic biofilm growth of Chlorella vulgaris to simultaneously improve microalgae biomass and lipid productivity.

In order to solve the technical bottleneck that the biomass yield and lipid accumulation cannot be increased simultaneously during microalgae growth, a heterotrophic-assisted photoautotrophic biofilm (HAPB) growth mode of Chlorella vulgaris was constructed. The light penetration capability of the microalgae biofilm formed through heterotrophic-assisted photoautotrophic growth was 64% stronger than that formed by photoautotrophic growth. Due to the different demands of autotrophic and heterotrophic growth of microalgae, the nutrient environment and growth conditions were optimized to fully utilize the advantages and potentials of the HAPB culture model. An optimized molar ratio of total inorganic carbon (CO2) to total organic carbon (glucose) (20:1) and a molar ratio of total carbon to total nitrogen (72:1) were obtained. The maximum specific growth rate of Chlorella vulgaris increased by 78% compared to that before optimization. Meanwhile, the lipid content and yield increased by 120% and 147%, respectively, up to 47.53% and 41.95 g m-2.

Effect of Sodium-Glucose Co-transporter 2 Inhibitors on Bone Metabolism and Fracture Risk.

The effect of anti-diabetic medications on bone metabolism has received increasing attention, considering that type 2 diabetes mellitus is a common metabolic disorder with adverse effects on bone metabolism. Sodium-glucose co-transporter 2 (SGLT2) inhibitors are novel anti-diabetic medications that prevent glucose resorption at the proximal convoluted tubules in the kidney, increasing urinary glucose excretion, and decreasing the blood glucose level. The superiority of SGLT2 inhibitors shows in reducing the glucose level independent of insulin secretion, lowering the risk of hypoglycemia, and improving cardiovascular outcomes. SGLT2 inhibitors have been associated with genital mycotic infections, increased risk of acute kidney injury, dehydration, orthostatic hypotension, and ketoacidosis. Moreover, the effect of SGLT2 inhibitors on bone metabolism and fracture risk has been widely taken into consideration. Our review summarizes the results of current studies investigating the effects of SGLT2 inhibitors on bone metabolism (possibly including increased bone turnover, disrupted bone microarchitecture, and reduced bone mineral density). Several mechanisms are probably involved, such as bone mineral losses due to the disturbed calcium and phosphate homeostasis, as confirmed by an increase in fibroblast growth factor 23 and parathyroid hormone levels and a decrease in 1,25-dihydroxyvitamin D levels. SGLT2 inhibitors might indirectly increase bone turnover by weight loss. Lowering the blood glucose level might ameliorate bone metabolism impairment in diabetes. The effect of SGLT2 inhibitors on bone fractures remains unclear. Evidence indicating the direct effect of SGLT2 inhibitors on fracture risk is lacking and increased falls probably contribute to fractures.