ABSTRACT
Objective The imbalance of glucagon secretion plays an important role in the development of diabetes. The newly discovered ACE2/Ang(1-7)/Mas pathway is an vital branch of the RAS system and has regulatory effects on islet function, but its effect on glucagon secretion is still unknown. The article aimed to investigate the effect and possible mechanisms of AVE0991, a Mas receptor agonist on glucagon secretion of diabetic db/db mice. Methods A tolal of 30 db/db mice were randomized to AVE group and model group (n=15), and their age-matched nondiabetic db/m mice were selected as the normal group (n=15). The mice in AVE group were treated with AVE0991 20mg/kg/d and those in model group were treated with placebo via gavage for 6 weeks. The metabolic indicators were measured every week. After 6 weeks of treatment, intraperitoneal glucose tolerance test (IPGTT) and islet perifusion were performed to evaluate glucagon release kinetics in vivo and vitro. Double-label immunofluoresence assay was adoppted to assess the content of α and β cells. Moreover, qRT-PCR and western blot were employed to detect the GCK expression in islets. Results The fasting blood sugar[(19.1±0.8)mmol/L] and glucose tolerance [(14.1±0.5) mU/L]of AVE group were significantly lower than those of the model group[(25.3±3.0)mmol/L,(17.3±1.8)mU/L](P＜0.05) and still higher than those of normal group[(6.3±0.5)mmol/L,(5.7±0.3)mU/L](P＜0.05). At the 30, 60, and 120 min after IPGTT, the blood glucose level and glucagon level in AVE group were lower than model group, but still higher than the normal group (P<0.05). During low glucose perfusion, the glucagon secretion level of the islets of normal group [(20.6±0.5 pmol/L)] was lower than that of model group [(29.1±0.7) pmol/L)] and AVE group [(27.6±0.8) Pmol/L], and the difference was statistically significant (P<0.05). During high glucose perfusion, there was a statistically significant difference in glucagon level between AVE group and model group at 30 and 60 min(P<0.05). Semi-quantitative analysis showed that the islet α-cell content of model group [(3.3±0.7) mg] was significantly higher than that of normal group [(1.2±0.3) mg] (P<0.05), and the β cell content [(2.4±0.6) mg] was significantly lower than that of normal group [(4.8±0.3) mg] (P<0.05); While compared with the model group, the islet α-cell content [(1.8±0.4) mg] decreased significantly (P<0.05) and the β-cell content [(4.2±0.5) mg] increased significantly in AVE group (P<0.05). The expression levels of GCK mRNA and protein in model group were lower than those in normal group (P<0.05). Conclusion Activation of Mas receptors can improve glucose metabolism by reducing the secretion of glucagon after glucose load in db/db diabetic mice. The mechanism may be related to the decrease of islet α cell content and the increase of islet GCK expression.
ABSTRACT
Objective To observe the c linical effect of scalp acupuncture combined with swallowing and speech therapeutic instrument for the treatment of post-stroke dysphagia. Methods Sixty-eight patients with post-stroke dysphagia were randomly divided into treatment group (N = 34)and control group (N = 34). Both groups were given the internal medicine treatment for lowering blood lipids,stabilizing plaque,and nourishing nerves,and took rehabilitation training. And additionally,the treatment group was given scalp acupuncture therapy and the treatment with swallowing and speech therapeutic instrument,and the control group was given the treatment with s wallowing speech therapeutic instrument alone. Two weeks constituted one treatment course, and the two groups were treated for 4 weeks. The scores of Standardized Swallowing Assessment(SSA) and Swallowing Quality of Life Instrument (SWAL-QOL) of the two groups were observed before and after treatment, and then the curative effects were evaluated by Saito 7-grade dysphagia assessment method. Results (1)Till the end of the trial,7 cases of the 68 patients were excluded for transferring to other departments or loss to follow-up. Of the 7 excluded cases, 3 cases were from the treatment group and 4 were from the control group. (2) The total effective rate of the treatment group was 90.32%and that of the control group was 66.67%,the difference being significant(P < 0.05).(3)After treatment,SSA scores of the 2 groups were decreased(P < 0.01)and SWAL-QOL scores were increased (P < 0.01),and the effect on improving SSA scores and SWAL-QOL scores in the treatment group was superior to that in the control group (P < 0.01). Conclusion Both groups can relieve dysphagia and improve the quality of life of post-stroke dysphagia patients,and the scalp acupuncture combined with swallowing and speech therapeutic instrument is more effective for the treatment of post-stroke dysphagia.