Effect of Mas receptor agonist activation on pancreatic α cell function of diabetic db/db mice by RAS non-classical pathway / 医学研究生学报

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.

Diagnostic criteria for late-onset hypogonadism: A preliminary study / 中华男科学杂志

<p><b>Objective</b>To determine the stability of androgen indexes by analyzing the relationship of androgen indexes with the results of late-onset hypogonadism (LOH) questionnaire investigations, and offer some reference for the application of the diagnostic criteria for LOH released by The Chinese Society of Andrology in 2009.</p><p><b>METHODS</b>This study included 1 003 males aged 40 years or older who had accomplished the questionnaires of Androgen Deficiency in Aging Males (ADAM), Aging Males' Symptoms Scale (AMS), and International Index of Erectile Function-5 (IIEF-5). We evaluated the correlation of androgen indexes with the results of the questionnaire investigation, repeated the examination of androgen indexes for the subjects with total testosterone (TT) ≤11.5 nmol/L after an average of 1.5 years, and analyzed the factors inducing changes of androgen indexes.</p><p><b>RESULTS</b>Free testosterone index (FTI) ≤ 0.42 (OR, 1.369) and calculated free testosterone (cFT) ≤ 0.3 nmol/L (OR, 1.302) were considered as the risk factors of LOH in AMS, and so were testosterone secretion index (TSI) ≤ 2.8 nmol/IU (OR, 1.679) and cFT ≤ 0.3 nmol/L (OR, 1.371) in IIEF-5. Paired t-test on the results of the examination performed twice showed significant differences in the levels of TT, TSI, cFT, and FT (P<0.05).</p><p><b>CONCLUSIONS</b>Decreased testosterone may cause the diversity of LOH symptoms and hence the fluctuation of androgens. Therefore, the diagnosis of LOH depends on androgen indexes, varied symptoms in the questionnaires, and relief of the symptoms after testosterone therapy.</p>

Association of serum testosterone with atherosclerosis in middle-aged and elderly men / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the association between the level of serum testosterone and atherosclerosis in middle-aged and elderly men.</p><p><b>METHODS</b>We conducted a population-based study of 413 males aged 40-75 years in a community in Guangzhou. We obtained the sociodemographic characteristics, clinical data, physical measurements, and laboratory results of sex hormones, blood glucose, and blood lipid of the subjects. We also measured the carotid intima media thickness (CIMT) by color Doppler ultrasonography.</p><p><b>RESULTS</b>The subjects were divided into a carotid atherosclerosis (CAS) group (CIMT ≥ 0.9 mm) and a non-CAS group (CIMT < 0.9 mm). The medians of free testosterone (FT) were 57.41 and 59.72 pmol/L in the CAS and non-CAS groups, respectively (P = 0.005), and no significant difference was found between the two groups in total testosterone (TT). The levels of serum FT and TT were negatively correlated to CIMT, with Spearman's rank correlation coefficients of -0.126 (P = 0.011) and -0.188 (P < 0.001), respectively. The incidence rates of CAS were 23.30, 13.46, 17.48, and 7.77% in the Q1, Q2, Q3, and Q4 groups, respectively according to the quartile of FT (P for trend = 0.008) and 17.48, 18.27, 16.50, and 9.71% respectively according to the quartile of TT (P for trend = 0.116). Based on the quartile of FT and after adjustment for age, waist circumference, systolic blood pressure, and HbAlc, the risk of CAS was significantly increased in the Q1 group as compared with Q4 (OR = 2.491, 95% CI 1.01-6.149), but no statistically significant differences were observed according to the quartile of TT.</p><p><b>CONCLUSION</b>A low serum FT level may be a risk factor of atherosclerosis in Chinese men aged 40 years or older.</p>

Etiologic factors of erectile dysfunction in men with type 2 diabetes mellitus / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the relationship of erectile dysfunction (ED) with blood vessel-, nerve- and androgen-related factors in young and middle-aged men with type 2 diabetes mellitus (T2DM) in order to provide some clinical evidence for early prevention and treatment of ED.</p><p><b>METHODS</b>We divided 53 male T2DM patients under 50 years into an ED group (IIEF-5 score < or = 21, n = 28) and a non-ED (NED) group (IIEF-5 score > or = 22, n = 25). We detected the levels of blood lipid, glucose, total testosterone (TT), sex hormone-binding globulin (SHBG), sulfate dehydroepiandrosterone (DHEA-S), calculated free testosterone (cFT), and examined the complications of macroangiopathy (MA), diabetic retinopathy (DR) and diabetic peripheral neuropathy (DPN), and compared the above indicators between the two groups.</p><p><b>RESULTS</b>There were no significant differences between the two groups in age, diabetes duration, body mass index, blood pressure, and blood lipid and glucose levels (P > 0.05). The incidence rate of DR was significantly higher in the ED than in the NED group (39.3% vs 4.0%, P < 0.05), but no statistically significant differences were found in the levels of TT, cFT, SHBG and DHEA-S and the incidence rates of MA and DPN between the two groups (P > 0.05).</p><p><b>CONCLUSION</b>The incidence of ED is closely related to DR in young and middle-aged men with T2DM. Therefore particular attention should be paid to the erectile function of T2DM patients with DR as early as possible.</p>

Multicenter clinical study on the efficacy and safety of inhalable insulin aerosol in the treatment of type 2 diabetes / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>A new inhalable insulin aerosol (Inh-Ins) was developed in China. The aim of this multicenter clinical study was to evaluate the efficacy and safety of this new Inh-Ins as a treatment of type 2 diabetes. Regular porcine insulin (RI) was used as a control.</p><p><b>METHODS</b>This study is a prospective, randomized, open-label, parallel-group multicenter clinical trial in which 253 qualified patients with type 2 diabetes received the insulin Glargine daily at bedtime plus either a pre-meal Inh-Ins or a pre-meal subcutaneous RI for 12 weeks. HbA1c, fasting plasma glucose (FPG), the 1-hour-postprandial blood glucose (1hPBG) and the 2-hour-postprandial blood glucose (2hPBG) were measured. Events were monitored for adverse effects.</p><p><b>RESULTS</b>After 12 weeks, the HbA1c decreased significantly from baseline in both treatment groups, with no significant difference between the two regimens. In the Inh-Ins group, FPG, both 1hPBG and 2hPBG significantly declined from baseline after the 8th- and 12th-weeks of treatment. The reduced values of FPG or 1hPBG between the two groups showed a more significant hypoglycemic effect with the Inh-Ins than the RI. After 12 weeks, the pulmonary carbon monoxide diffusing capacity (DLco) was significantly lower in Inh-Ins group than in the RI. The main side effects of Inh-Ins were coughing, excessive sputum, and hypoglycemia.</p><p><b>CONCLUSIONS</b>Inh-Ins was effective in decreasing HbA1c like the RI. It was better in lowering the FPG and the 1hPBG than the RI. Its main side effects were coughing, excessive sputum, and hypoglycemia. Also, Inh-Ins slightly impaired DLco.</p>

Effects of transfection with recombinant adiponectin adeno-associated virus vectors (rAAV-Ad) on glucose production in H4IIE hepatoma cells / 中华内分泌代谢杂志

H4IIE hepatoma cells transfected by recombinant adiponectin adeno-associated virus vectors were effectively mediated adiponectin gene expression and enhanced the ability of suppressing glucose production of H4IIE cells at low concentration of insulin.Improvement of the insulin sensitivity in hepatocytes may contribute to the glucose-lowering effect of adiponectin.