Rheb1 promotes glucose-stimulated insulin secretion in human and mouse ß-cells by upregulating GLUT expression.

Reduced ß-cell mass and impaired ß-cell function are primary causes of all types of diabetes. However, the intrinsic molecular mechanism that regulates ß-cell growth and function remains elusive. Here, we demonstrate that the small GTPase Rheb1 is a critical regulator of glucose-stimulated insulin secretion (GSIS) in ß-cells. Rheb1 was highly expressed in mouse and human islets. In addition, ß-cell-specific knockout of Rheb1 reduced the ß-cell size and mass by suppressing ß-cell proliferation and increasing ß-cell apoptosis. However, tamoxifen-induced deletion of Rheb1 in ß-cells had no significant effect on ß-cell mass and size but significantly impaired GSIS. Rheb1 facilitates GSIS in human or mouse islets by upregulating GLUT1 or GLUT2 expression, respectively, in a mTORC1 signaling pathway-dependent manner. Our findings reveal a critical role of Rheb1 in regulating GSIS in ß-cells and identified a new target for the therapeutic treatment of diabetes mellitus.

The effects of vitamin and mineral supplementation on women with gestational diabetes mellitus.

BACKGROUND: The effects of vitamin and mineral supplementation on women with gestational diabetes mellitus (GDM) have not been well established. We conduct a meta-analysis to evaluate the effects of vitamin and mineral supplementation on glycemic control, inflammation and oxidative stress for women with GDM. METHODS: A systematic search of randomized controlled trials (RCTs) was conducted from PubMed, Embase, Web of Science and Cochrane Library up to July, 2020. Various results were pooled by using Review manager 5.3 and Stata 12.0. Mean difference (MD) with 95% confidence interval (CI) was estimated. Heterogeneity between studies was assessed by I-squared (I2) tests. RESULTS: Six hundred ninety-eight patients from 12 trials were included in our meta-analysis. Magnesium, zinc, selenium, calcium, vitamin D and E (alone or in combination) were found to significantly improve glycemic control in women with GDM compared to those receiving placebos: fasting plasma glucose (FPG) (MD = - 9.02; 95% CI: - 12.09, - 5.96; P < 0.00001), serum insulin (MD = - 4.33; 95% CI: - 5.35, - 3.32; P < 0.00001), homeostasis model assessment-insulin resistance (HOMA-IR) (MD = - 1.34; 95% CI: - 1.60, - 1.07; P < 0.00001), and homeostasis model of assessment for ß cell function (HOMA-B) (MD = - 15.58; 95% CI: - 23.70, - 7.46; P = 0.0002). Vitamin and mineral supplementation was found to attenuated inflammation and oxidative stress through decreasing high-sensitivity C-reactive protein (hs-CRP) (MD = - 1.29; 95% CI: - 1.82, - 0.76; P < 0.00001), malondialdehyde (MDA) (MD = - 0.71; 95% CI: - 0.97, - 0.45; P < 0.00001), and increasing total antioxidant capacity (TAC) (MD = 45.55; 95% CI: 22.02, 69.08; P = 0.0001). CONCLUSIONS: This meta-analysis shows that vitamin and mineral supplementation significantly improved glycemic control, attenuated inflammation and oxidative stress in women with GDM.

Efficacy and safety of DPP-IV inhibitors combined with basal insulin in the treatment of type 2 diabetes.

BACKGROUND: To evaluate the efficacy and safety of dipeptidyl peptidase IV (DPP-IV) inhibitors when added to insulin therapy in patients with type 2 diabetes mellitus (T2DM). METHODS: PubMed, EMBASE, the Web of Science, and the Cochrane Library were systematically searched for randomized controlled trials (RCTs) exploring the efficacy or safety of DPP-IV inhibitors in T2DM patients. The quality of the included RCTs was assessed with the Cochrane risk-of-bias tool. For outcomes, odds ratios or weighted mean differences (WMDs) with 95% CIs were calculated using both random- and fixed-effects models. RESULTS: A total of 16 studies were included in the meta-analysis with 5418 participants. Glycosylated hemoglobin (HbA1c) was significantly decreased in the DPP-IV inhibitors with insulin (DPP-IVi/INS) group compared with the insulin-alone (with or without placebo) group (WMD = -0.62%; 95% CI: -0.74, -0.49; P < .05). Consistent with this finding, the fasting blood glucose (FBG)-lowering effect (WMD = -0.61 mmol/L; 95% CI: -0.77, -0.45; P < .05) and 2-hour postprandial glucose (2hPPG)-lowering efficacy (WMD = -2.39 mmol/L; 95% CI: -2.81, -1.97; P < .05) in the DPP-IVi/INS group were also significantly better than in the insulin-alone group. Regarding safety indicators, compared with the insulin-alone group, DPP-IVi/INS treatments had no association with the risk of adverse effects, including hypoglycemia, adverse events (AEs), and serious adverse events (SAEs). CONCLUSIONS: Compared with insulin treatment alone, treatment with DPP-IVi/INS improved HbA1c, FBG, and 2hPPG without increasing the risk of hypoglycemia, AEs, or SAEs.

Murine Appendectomy Model of Chronic Colitis Associated Colorectal Cancer by Precise Localization of Caecal Patch.

The human appendix has been recently implicated to play important biological roles in the pathogenesis of various complex diseases, such as colorectal cancer, inflammatory bowel disease, and Parkinson's disease. To study the function of the appendix, a gut disease-associated murine appendectomy model has been established and its step-by-step protocol is described here. This report introduces a facile protocol for caecal patch removal in mice followed by the chemical induction of chronic colitis-associated colorectal cancer using a combination of dextran sulfate sodium (DSS) and azoxymethane (AOM). IgA specific cells and IgA concentration were significantly reduced upon removal of the caecal patch in male C57BL/6 mice compared to those in the sham group. Simultaneously administering 2% DSS and AOM resulted in nearly 80% mice survival in both sham and appendectomy groups without significant body weight loss. Histological results confirmed colonic inflammation and different degrees of adenocarcinoma. This model can be used for the study of the functional role of the appendix in maintaining gut microbiota homeostasis and pathogenesis of gut colitis and malignancies, as well as for the potential development of drug targeting therapies.

Dose Effects of Orally Administered Spirulina Suspension on Colonic Microbiota in Healthy Mice.

Oral supplemented nutraceuticals derived from food sources are surmised to improve the human health through interaction with the gastrointestinal bacteria. However, the lack of fundamental quality control and authoritative consensus (e.g., formulation, route of administration, dose, and dosage regimen) of these non-medical yet bioactive compounds are one of the main practical issues resulting in inconsistent individual responsiveness and confounded clinical outcomes of consuming nutraceuticals. Herein, we studied the dose effects of widely used food supplement, microalgae spirulina (Arthrospira platensis), on the colonic microbiota and physiological responses in healthy male Balb/c mice. Based on the analysis of 16s rDNA sequencing, compared to the saline-treated group, oral administration of spirulina once daily for 24 consecutive days altered the diversity, structure, and composition of colonic microbial community at the genus level. More importantly, the abundance of microbial taxa was markedly differentiated at the low (1.5 g/kg) and high (3.0 g/kg) dose of spirulina, among which the relative abundance of Clostridium XIVa, Desulfovibrio, Eubacterium, Barnesiella, Bacteroides, and Flavonifractor were modulated at various degrees. Evaluation of serum biomarkers in mice at the end of spirulina intervention showed reduced the oxidative stress and the blood lipid levels and increased the level of appetite controlling hormone leptin in a dose-response manner, which exhibited the significant correlation with differentially abundant microbiota taxa in the cecum. These findings provide direct evidences of dose-related modulation of gut microbiota and physiological states by spirulina, engendering its future mechanistic investigation of spirulina as potential sources of prebiotics for beneficial health effects via the interaction with gut microbiota.

Clinical effect of treating renal transplant recipients with percutaneous coronary intervention and its safety.

OBJECTIVE: To explore clinical effect of treating acute coronary syndrome (ACS) of renal transplant recipients with percutaneous coronary intervention and its safety. METHODS: Forty two renal transplant recipients who were diagnosed with acute coronary syndrome and received percutaneous coronary intervention (PCI) in our hospital were selected. Serum creatinine (Cr) and glomerular filtration rate (GFR) were compared before surgery, 48 ~ 72 hour after surgery and one year after surgery. All patients were followed up. RESULTS: All patients successfully completed PCI. Contrast-induced nephropathy was not found after surgery. Cr and GFR 48 ~ 72 hour after surgery and one year after surgery had no significant differences with that before surgery (P>0.05). The follow up lasted for (61.2±32.2) months averagely. Of 42 cases, 4 cases died, 6 cases were found with nonfatal myocardial infarction, 4 cases were observed with repeat revascularization and 12 cases had accumulative major adverse cardiovascular events (MACE). CONCLUSION: PCI is proved to be effective in treating renal transplant recipients; no severe complications are found and renal function recovers well after treatment.