Ghrelin may have therapeutic value in mitigating insulin resistance and type 2 diabetes, based on which we further explore the action mechanism of ghrelin on islet cells in this research. In the course of experiments, MIN6 cells were induced by glucose and then treated with acylated or unacylated ghrelin. The effects of ghrelin on the viability, proliferation, apoptosis, and insulin release of high glucose‐induced islet cells were detected by Cell Counting Kit‐8, 5‐ethynyl‐2′‐deoxyuridine, flow cytometry, and enzyme‐linked immunosorbent assays, respectively. Meanwhile, cells were treated with LY294002 to explore whether and how the inhibited phosphoinositide 3‐kinase–protein kinase B (PI3K–AKT) signaling pathway participated in the internal mechanism of ghrelin‐regulating islet cells. Western blotting was performed to quantify the expression levels of Bcl‐2, Bax, Cleaved caspase‐3, PI3K, and AKT. As a result, ghrelin alleviated high glucose‐induced suppression of viability and proliferation and promotion on apoptosis of MIN6 cells. Ghrelin also attenuated the inhibitory effects of high glucose on expression levels of PI3K–Akt signaling axis‐related proteins and insulin release in MIN6 cells. Besides, ghrelin weakened the impacts of high glucose on boosting MIN6 cell apoptosis and hindering proliferation through the PI3K–Akt signaling axis. Collectively, ghrelin regulates the proliferation and apoptosis of high glucose‐induced islet cells through the PI3K–Akt signaling pathway.

Background:Osteocalcin is a sort of protein secreted by osteoblast exclusively，and new observations have verified that glucose balance can be modulated by it in some ways. TIR has attracted more and more attention as an emerging blood glucose evaluation index. In this study, the association between TIR and the level of circulating osteocalcin was investigated in type 2 diabetes.METHODS376 patients with type 2 diabetes were enrolled in our trail, all of them performed three consecutive days of monitoring. And they were divided into four groups on account of the quartile of osteocalcin. TIR, Time below range(TBR）, Time above range(TAR) and measures of glycemic variability (GV) were assessed for analysing. After a 100g standard steamed bread meal, blood glucose (Glu0h Glu0.5h, Glu1h, Glu2h, GLu3h), C-peptide (Cp0h, Cp0.5h, Cp1h, Cp2h, Cp3h), serum insulin (INS0h, INS0.5h, INS1h, INS2h, INS3h) concentrations at different time points were obtained. HOMA-IS, HOMA-β was calculated to evaluate insulin sensitivity and insulin secreting of the participants.RESULTSTIR increased significantly as the osteocalcin level increased between groups (p < 0.05). No significant differences were found in gender composition, age, weight, BMI, diabetes duration, K+, Ca+, Creatinine, blood pressure among groups (respectively, p>0.05). Osteocalcin had positive correlation with TIR (r=0.227, P<0.001), while a negative correlation was presented in osteocalcin and TAR (-0.229, P< 0.001). Likewise, osteocalcin was negatively correlated with INS0h, INS0.5h, fasting blood glucose and postprandial blood glucose at any time point after intaking of a standard meal.Meanwhile, osteocalcin had a negative correlation with the majority of GV indexes including standard deviation (SD), mean blood glouse (MBG), mean of daily differences (MODD), average daily danger range (ADDR). Multiple stepwise regression analysis demonstrated that osteocalcin was an independent contributor of TIR, TAR, and HOMA-IS.CONCLUSIONSCirculating osteocalcin has a positive correlation with TIR, and is an protective factor of TIR and insulin sensitivity in type 2 diabetic patients.