Recombinant betatrophin (Angptl­8/lipasin) ameliorates streptozotocin­induced hyperglycemia and ß­cell destruction in neonatal rats.

Betatrophin [also known as lipasin, angiopoietin­like 8 (ANGPTL8), refeeding induced in fat and liver (RIFL), or hepatocellular carcinoma­associated gene TD26], a 22­kDa protein in the angiopoietin­like family, is a liver­derived hormone that promotes pancreatic ß­cell proliferation and lipid metabolism. The aim of the present study was to investigate the effect of recombinant betatrophin on ß­cell regeneration in a neonatal streptozotocin (STZ)­induced diabetic rat model. One­day­old Wistar rats were injected with STZ (100 mg/kg), followed by intraperitoneal administration of betatrophin to the STZ­injected rats for 6 days. Plasma glucose and body weight were monitored. On days 4 and 7, expression levels of pancreatic duodenal homeobox gene­1 (PDX­1), the Bax/B­cell lymphoma­2 (Bcl­2) ratio and plasma insulin were assessed, and the ß­cell proliferation rate was determined. Pancreatic islet area and number were determined at 10 weeks. It was found that betatrophin treatment alleviated STZ­induced hyperglycemia, elevated pancreatic expression levels of Bcl­2, PDX­1, plasma insulin levels and the ß­cell proliferation rate on days 4 and 7. Long­term betatrophin treatment improved glucose tolerance, associated with improved plasma insulin levels and ß­cell mass. These results suggest that early administration of betatrophin promotes ß­cell proliferation in STZ­induced diabetic neonates and prevents the development of diabetes in adults.

Effects of Lifestyle Modification and Anti-diabetic Medicine on Prediabetes Progress: A Systematic Review and Meta-Analysis.

Background: Pre-diabetes is a risk factor for full-blown diabetes; it presents opportunities to prevent the actual diseases. It is therefore essential to identify effective preventive strategies, and to clarify the direction of future research. Methods: PubMed, Embase and Cochrane Central Register of Controlled Trials were searched using key terms (Supplementary Table 1). We applied network meta-analysis to multiple comparisons among various diabetic preventive strategies, including lifestyle and pharmacological interventions; traditional meta-analysis for the synthesis of basal metabolic changes after interventions; and trial sequential analysis for determinations as to whether analysis conclusions meet expectations. Results: We included 32 randomized controlled trials comprising 43,669 patients and 14 interventions in the meta-analysis. Both lifestyle modifications and anti-diabetic medications improved physical conditions, including weight loss, blood glucose, and blood pressure. Network meta-analysis suggested that the progression of diabetes could be delayed to varying degrees by lifestyle and pharmacological interventions, except for angiotensin-converting enzyme inhibitors, statins, sulfonylureas and vitamin D. The risk ratios (RR) [95% credible interval (CrI)] compared with control were: GLP-1RAs 0.28 (0.15, 0.50), Orlistat 0.33 (0.18, 0.55), TZM 0.33 (0.16, 0.63), TZD 0.39 (0.27, 0.53), LST 0.54 (0.32, 0.88), lifestyle 0.58 (0.49, 0.67), LSM 0.62 (0.45, 0.80), GI 0.66 (0.46, 0.88), SU 0.67 (0.40, 1.00), Vitamin D 0.91 (0.59, 1.40), ACEI 0.93 (0.62, 1.40), statins 1.20 (0.84, 1.60). Conclusions: In adults with pre-diabetes, firm evidence supports the notion that lifestyle modifications and metformin reduces the incidence of diabetes with an average of 20% relative risk reduction, while statins increase the relative risk 20%. We found that lifestyle modifications, promising long-term strategies involving three factors (nutrition, exercise, and weight loss) contribute to health by reducing BMI, body weight, waist and hip circumference, systolic and diastolic pressure, fasting, and 2-h postprandial blood glucose, total cholesterol and by increasing HDL. We made this determination using TSA, avoiding further waste of experimental resources.

Correction to: Systematic Review and Meta-Analysis of the Change in Ghrelin Levels After Roux-en-Y Gastric Bypass.

This article was initially published with incorrect copyright information. Upon publication of this correction, the copyright of this article changed to "The Author(s)." The original article has been corrected.

The burden of air pollution and weather condition on daily respiratory deaths among older adults in China, Jinan from 2011 to 2017.

The health effects of short-term exposure to air pollutants on respiratory deaths and its modifiers such as meteorological indexes have been widely investigated. However, most of the previous studies are limited to single pollutants or total respiratory deaths, and their findings are inconsistent.To comprehensively examine the short-term effects of air pollutants on daily respiratory mortality.Our analysis included 16,931 nonaccidental respiratory deaths (except lung cancer and tuberculosis) among older adults (>65 years) from 2011 to 2017 in Jinan, China. We used a generalized additive Poisson models adjusted for meteorology and population dynamics to examine the associations between air pollutants (particulate matter with an aerodynamic diameter of b2.5µm [PM2.5], particulate matter with an aerodynamic diameter of b10µm [PM10], SO2, NO2, O3) and daily mortality for the total patients, males, females, chronic airway diseases, pneumonia patients, and rest patients in Jinan.Outdoor air pollution was significantly related to mortality from all respiratory diseases especially from chronic airway disease in Jinan, China. The effects of air pollutants had lag effects and harvesting effects, and the effects estimates usually reached a peak at lag 1 or 2 day. An increase of 10 µg/m or 10 ppb of PM2.5, PM10, SO2, NO2, and O3 corresponds to increments in mortality caused by chronic airway disease of 0.243% (95% confidence interval [CI]: -0.172-0.659) at lag 1 day, 0.127% (95% CI: -0.161-0.415) at lag 1 day, 0.603% (95% CI: 0.069-1.139) at lag 3 day, 0.649% (95% CI: -0.808-2.128) at lag 0 day and 0.944% (95% CI: 0.156-0.1598) at lag 1 day, respectively. The effects of air pollutants were usually greater in females and varied by respiratory subgroups. Spearman correlation analysis suggested that there was a significant association between meteorological indexes and air pollutants.Sex, age, temperature, humidity, pressure, and wind speed may modify the short-term effects of outdoor air pollution on mortality in Jinan. Compared with the other pollutants, O3 had a stronger effect on respiratory deaths among the elderly. Moreover, chronic airway diseases were more susceptible to air pollution. Our findings provided new evidence for new local environmental and health policies making.

Systematic Review and Meta-analysis of the Change in Ghrelin Levels After Roux-en-Y Gastric Bypass.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) is considered effective for weight loss and for treatment of many obesity-related metabolic diseases. Ghrelin is an essential orexigenic peptide that plays an indispensable role in controlling body weight and energy homeostasis of post-operative patients. This systematic review and meta-analysis aimed to investigate changes in the level of fasting total ghrelin following RYGB. METHODS: A systematic literature search of PubMed, EMBASE, and the Cochrane Library until April 2018 with keywords "ghrelin" and "gastric bypass" was performed in accordance with the MOOSE guidelines and PRISMA statement. Three reviewers independently selected the studies and extracted data. Quality assessment of the included studies was undergone. A random effects model was employed to calculate overall effect sizes. Subgroup analyses and meta-regression were subsequently performed. RESULTS: Sixteen studies with 325 patients were included. We found ghrelin levels had an increasing tendency (SMD = 0.30; 95% CI = 0.04 to 0.57) despite moderate heterogeneity (I2 = 58%). Subsequent subgroup analysis indicated that ghrelin levels decreased (SMD = - 0.49; 95% CI = - 0.98 to 0.00) in the short term (≤ 3 months) and increased (SMD = 0.46; 95% CI = 0.22 to 0.69) in the long term (> 3 months) after RYGB. Meta-regression showed that gastric pouch volume, alimentary limb length and biliopancreatic limb length were not associated with changes in ghrelin levels. CONCLUSION: Fasting total ghrelin levels decreased in the short term (≤ 3 months) and increased in the long term (> 3 months) after RYGB.

Ghrelin Receptor Is Required for the Effect of Nesfatin-1 on Glucose Metabolism.

Studies of nesfatin-1 in glucose metabolism have become a topic of interest recently, however, the specific receptor for nesfatin-1 has not yet been identified. Some studies hinted at a connection between nesfatin-1 and the ghrelin receptor, growth hormone secretagogue receptor. Therefore, we aimed to study the role of GHSR in the glycemic effects of nesfatin-1 as well as its downstream pathways. We employed C57/BL6 mice (wild type and GHSR knockout mice) eating a normal chow diet and a high fat diet in this study, and the experimental technique included western blot, real-time PCR, immunofluorescence and ELISA. We found that in mice fed a normal chow diet (NCD), nesfatin-1 improved glucose tolerance, up-regulated AKT kinase (AKT) mRNA levels and phosphorylation and GLUT4 membrane translocation in skeletal muscle. These effects were blocked by co-injection of GHSR antagonist [D-Lys3]-GHRP-6 and were attenuated in GHSR knockout mice. In mice fed high-fat diet (HFD), nesfatin-1 not only exerted the effects observed in NCD mice, but also suppressed appetite and raised AKT levels in liver tissues that also required GHSR. Peripheral nesfatin-1 suppressed c-fos expression of GHSR immunoreactive neurons induced by fasting in hypothalamic nuclei, indicating that nesfatin-1 inhibited the activation of central GHSR. We concluded that the effects of nesfatin-1 on food intake and glucose metabolism were GHSR-dependent, and that the glycemic effect was associated with AKT and GLUT4. This study should stimulate further exploration of the nesfatin-1 receptor.

The Correlation Between Circulating Ghrelin and Insulin Resistance in Obesity: A Meta-Analysis.

Background: Ghrelin, a peptide mainly produced by stomach X-A cells. It plays a pivotal role in the regulation of food intake and energy metabolism, including glucose metabolism and insulin sensitivity. However, the correlation between circulating ghrelin levels and insulin resistance in obesity remained uncertain. This meta-analysis aimed to clarify the association between ghrelin and IR in obesity. Methods: A systematic literature search was performed using PubMed, EMBASE, Cochrane Library and Web of Science until April 18, 2018 with the keywords "ghrelin" and "insulin resistance." Two independent reviewers selected studies and assessed data. Subgroup analyses were performed to search for sources of heterogeneity. Funnel plots and Egger's test were used to detect publication bias. A random-effects model was used to calculate the pooled effect size. Results: Ten studies with 546 participants were included in this meta-analysis. We found that ghrelin levels were negatively correlated with IR in obese individuals. (r = -0.31; 95% CI: -0.45 to -0.18). Subgroup analysis revealed that circulating ghrelin levels were significantly negatively correlated with IR in people with normal fasting blood glucose (FBG) (<6.9 mmol/dl) (r = -0.28; 95% CI: -0.47 to -0.09, I 2 = 39.5%), while there was no relationship between circulating ghrelin levels and IR in the high FBG group (>6.9 mmol/dl) (r = -0.15; 95% CI: -0.33 to 0.03, I 2 = 0.0%). Publication bias was insignificant (Egger's test: P = 0.425). Conclusion: In obesity, circulating ghrelin levels were significantly negative correlated with insulin resistance in individuals with normal fasting blood glucose.