Ghrelin regulates the endoplasmic reticulum stress signalling pathway in gestational diabetes mellitus.

OBJECTIVE: We aimed to investigate the effects and mechanisms of the ghrelin-regulated endoplasmic reticulum stress (ERS) signalling pathway in gestational diabetes mellitus (GDM). METHODS: Pregnant female C57BL/6 mice were randomly divided into a normal group, GDM group (high-fat diet + STZ), GDM + ghrelin group (acyl ghrelin), and GDM + ghrelin + ghrelin inhibitor group ([D-lys3]-GHRP-6). We measured body weight, the intake of water and food, glucose, cholesterol, triglyceride and fasting insulin levels in each group. HE staining was used to observe the morphological changes in the pancreas. The TUNEL method was used to detect the apoptosis rate of islet cells. qPCR and Western boltting were performed to detect the relative expression levels of PERK, ATF6, IREIα, GRP78, CHOP and caspase-12, which are related to the ERS signalling pathway in the pancreas. Then, NIT-1 cells were cultured to verify whether ghrelin regulates ERS under high-glucose or tunicamycin conditions. RESULTS: Compared with the GDM group, the GDM + ghrelin group showed improved physical conditions and significantly decreased the fasting blood glucose, glucose tolerance, cholesterol, triglyceride and fasting insulin levels. Damaged islet areas were inhibited by ghrelin in the GDM group. The GDM + ghrelin group showed reduced ß-cell apoptosis compared to the GDM and GDM + ghrelin + ghrelin inhibitor groups. ERS-associated factors (PERK, ATF6, IREIα, GRP78, CHOP and caspase-12) mRNA and protein levels were obviously lower in the GDM + ghrelin group than in the GDM group, while expression levels were restored in the inhibitor group. Ghrelin treatment improved the high-glucose or tunicamycin-induced apoptosis, increased insulin levels and upregulation of GRP78, CHOP and caspase-12 in NIT-1 cells. CONCLUSION: Ghrelin suppressed ERS signalling and apoptosis in GDM mice and in NIT-1 cells. This study established a link between ghrelin and GDM, and the targeting of ERS with ghrelin represents a promising therapeutic strategy for GDM.

Hybrid versus traditional cardiac rehabilitation models: a systematic review and meta-analysis.

BACKGROUND: The common drawbacks of standard cardiac rehabilitation (CR) models include low participation rate, high cost, and dependence on on-site exercise sessions. Therefore, hybrid CR protocols have been developed. AIM: We aimed to test whether hybrid CR models are superior or equivalent to the traditional CR models in patients after myocardial infarction, heart failure, and cardiac surgery, using a meta-analysis framework. METHODS: Data from relevant original studies indexed in the Medline, Scopus, Cochrane Central, and Web of Science data-bases were extracted and analysed. The standardised mean difference (SMD) was used as a summary effect estimate, along with 95% confidence interval (CI). RESULTS: Based on data from 1195 patients, the summary effect size showed similar improvement in functional capacity in hybrid and standard CR programmes (SMD = -0.04, 95% CI -0.18 to 0.09, p = 0.51). No significant difference was detected between the two models in terms of changes in exercise duration (SMD = -0.14, 95% CI -0.51 to 0.24, p = 0.47), systolic (SMD = -0.01, 95% CI -0.14 to 0.12, p = 0.91), and diastolic (SMD = -0.03, 95% CI -0.16 to 0.11, p = 0.7) blood pres-sure, or health-related quality of life (SMD = -0.08, 95% CI -0.23 to 0.07, p = 0.27). In terms of blood lipids, no significant difference was noted between hybrid and traditional CR models in all assessed lipid profile parameters, except for triglycerides (favouring the traditional CR model). CONCLUSIONS: Hybrid CR protocols showed comparable efficacy to the traditional model. Further well-designed studies are required to validate these findings, especially regarding the long-term outcomes.