Effect of interlukin-22 antibody on diabetic nephropathy via inhibition on Snail1 expression / 中国病理生理杂志

AIM:To investigate the effect of interlukin-22(IL-22)on diabetic nephropathy(DN)and its possible mechanism.METHODS: C57BL/6 mice were randomized to normal control(NC)group,DN group, DN+recombinant IL-22(rIL-22)group and DN+IL-22 antibody(anti-IL-22)group.After successful establishment of diabetes model for 8 weeks,the mice in DN+rIL-22 group and DN+anti-IL-22 group were intraperitoneally injected with rIL-22(200 μg/kg)and anti-IL-22(200 μg/kg),respectively,and the mice in NC group and DN group were intraperito-neally injected with 0.1%bovine serum albumin,twice a week for 4 weeks.After the intervention,blood glucose,kidney function,24 h urine microalbumin(m-Alb)and 24 h urine creatinine(Ucr)were measured.The pathological changes of renal tissues were observed under light microscope.The mRNA expression of Snail1 was detected by qPCR.The protein levels of fibronetin(FN)and E-cadherin were determined by Western blot.RESULTS:After the intervention,the ratio of 24 h m-Alb/Ucr increased significantly in other model groups compared with NC group(P<0.05).The levels of 24 h m-Alb and 24 h Ucr increased significantly in DN +rIL-22 group compared with DN group(P<0.05).However,in DN+anti-IL-22 group,the levels of 24 h m-Alb,24 h Ucr and 24 h m-Alb/Ucr ratio were significantly lower than those in DN group and DN+rIL-22 group(P<0.05).The tubular epithelial cell vacuolar degeneration,protein cast formation and glo-merular mesangial expansion in the renal tissues from diabetic mice were observed under light microscope.The lesions were more severe in DN+rIL-22 group,but attenuated in DN+anti-IL-22 group.The mRNA expression of Snail1 increased sig-nificantly in diabetic mice(P<0.05),but decreased significantly after a 4-week intervention by anti-IL-22(P<0.05). The expression of FN,an extracellular matrix protein,increased significantly in DN +rIL-22 group(P<0.05).The ex-pression of E-cadherin,an epithelial-mesenchymal transition marker,decreased significantly in DN +rIL-22 group as well (P<0.05).CONCLUSION: IL-22 neutralizing antibody may attenuate microalbuminuria and delay the progression of DN via inhibition of Snail1 expression in the renal tubular epithelial cells.

Regulatory effect of liraglutide on the expression of eNOS in the corpus cavernosum of diabetic rats / 中华男科学杂志

<p><b>UNLABELLED</b>OCTOBER: To explore the effects of the glucagon-like peptide 1 (GLP-1) liraglutide on the penile erectile function of rats with diabetic erectile dysfunction (DED) by observing the impact of liraglutide on the expression of eNOS in the corpus cavernosum of diabetic rats.</p><p><b>METHODS</b>We randomly divided 30 six-week-old male SD rats into a normal control (n = 10) and an experimental group (n = 20) , established models of diabetes mellitus (DM) in the experimental rats, and subdivided them into a DM (n = 8) and a GLP-1 group (n = 8) to receive intramuscular injection of normal saline and liraglutide at 5 mg per kg of the body weight per day, respectively. After 12 weeks of intervention, we obtained the levels of FPG, FINS, TG, TC, HDL-C, LDL-C, testosterone, and IL-6 and the indexes of Homa-IR and Homa-β, detected the expressions of Akt/p-Akt and eNOS/p-eNOS in the corpus cavernosum by Western blot, and compared the erectile function between different groups.</p><p><b>RESULTS</b>The frequency and rate of penile erection were significantly lower in the DM group than in the GLP-1 and normal control groups (P < 0.05) and also lower in the GLP-1 group than in the normal controls (P < 0.05). Immunofluorescence staining showed the expression of eNOS mainly in the cytoplasm of the cavernosal vessels and sinusoidal endothelial cells, markedly lower in the DM and GLP-1 groups than in the normal rats (P < 0.05), but higher in the GLP-1 than in the DM group (P < 0.05). The level of eNOS/p-eNOS in the penile tissue was significantly decreased in the DM and GLP-1 groups in comparison with the normal controls (P < 0.01 or P < 0.05), while that of p-eNOS was markedly increased in the GLP-1 group as compared with the DM group (P < 0.05). No statistically significant differences were observed in the Akt level among the three groups of animals (P > 0.05). The expression of p-Akt was remarkably reduced in the DM and GLP-1 groups in comparison with the control rats (P < 0.01 or P < 0.05), but higher in the GLP-1 than in the DM group (P < 0.05).</p><p><b>CONCLUSION</b>GLP-1 can protect the function of endothelial cells in the corpus cavernosum and improve the erectile function of DED rats by regulating the Akt/ eNOS signaling pathway, which indicates that GLP-1 could be an important option for the treatment and prevention of DED.</p>

Clinical evaluation of valsartan and metoprolol tartrate in treatment of diabetic nephropathy with positive β1-adrenergic and anti-angiotensin II type 1 receptor antibody / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Studies have confirmed that angiotensin II receptor blocker (ARB) and angiotensin converting enzyme inhibitors (ACEI) in the treatment of diabetic nephropathy (DN) has special advantages. We observed the effects of valsartan and metoprolol tartrate hydrchloride in treatment of DN patients with positive β1-adrenergic and anti-angiotensin II type 1 (AT1) receptor antibody.</p><p><b>METHODS</b>The epitopes of the second extracellular loop of β1 receptor (197 - 222) and AT1 receptor (165 - 191), were synthesized and used respectively to screen serum autoantibodies from patients with DN (n = 371, group A), diabetes mellitus (DM) without renal failure (n = 107, group B) and healthy blood donors (n = 47, control, group C) by enzyme-linked immunosorbent assay (ELISA). Metoprolol tartrate 25 - 50 mg, three times per day, valsartan 160 mg, once a day, aspirin 100 mg, once a day, and nitrendipine 10 - 20 mg, three times per day, were given to DN patients with positive or negative autoantibodies. The cystatin C level and 24-hour urinary protein were measured before and after treatment.</p><p><b>RESULTS</b>In DN patients, the positive rate of the autoantibodies against β1 receptors and AT1 receptor was 47.7% and 51.5%, respectively, which were significantly higher than those in DM patients and healthy controls (all P < 0.01). Patients with anormalous cystatin C had higher positive rates of the autoantibodies than patients with normal cystatin C. Valsartan and metoprolol tartrate reduced proteinuria significantly (P < 0.01) in DN patients with positive autoantibodies.</p><p><b>CONCLUSIONS</b>The findings suggest that these autoantibodies against β1 and AT1-receptor may play important roles in the pathogenesis of DN. Valsartan and metoprolol tartrate are effective and safe in the treatment of DN.</p>

Positive rate of autoantibodies against adrenergic receptors beta1 and angiotensin II type 1 receptors in the type 2 diabetes mellitus with or without hypertension / 中华心血管病杂志

<p><b>OBJECTIVE</b>To observe the positive rates of autoantibodies against beta1 adrenergic receptors (beta1-receptor) and angiotensin II type 1 receptors (AT(1)-receptor) in type 2 diabetes patients with or without hypertension.</p><p><b>METHODS</b>The epitopes of the second extracellular loop of beta1-receptor (197 - 222) and AT(1) receptor (165 - 191) were synthesized and serum autoantibodies were determined in type 2 diabetes patients with hypertension (n = 171) or without hypertension (n = 106). Left ventricular dimension was determined by echocardiography. The 24-hour urinary protein was measured by ELISA. The risk factors for enlarged left ventricle were analyzed by multiple logistic regressions.</p><p><b>RESULTS</b>The positive rates of the autoantibodies against beta1-receptors (45.0%) and AT(1)-receptor (46.2%) in patients with type 2 diabetes with hypertension were significantly higher than those in patients with type 2 diabetes without hypertension (16.0% and 10.4%, respectively, all P < 0.01). In type 2 diabetes patients with hypertension and enlarged left ventricle, the positive rates of the autoantibodies against beta1-receptor 61.4% (35/57) and against AT(1)-receptor 64.9% (37/57)were significantly higher than those in type 2 diabetes patients with normal left ventricular dimension (36.8%, 42/114 and 36.8%, 42/114, respectively, all P < 0.01). Regression analysis demonstrated that course of disease, systolic pressure, serum autoantibodies against beta1 adrenergic receptor and angiotensin II type 1 receptors sera autoantibodies were independent risk factors for left ventricular enlargement (all P < 0.05).</p><p><b>CONCLUSION</b>The serum beta1 and AT(1)-receptor autoantibodies are related to enlarged left ventricle in type 2 diabetes patients with hypertension and suggest that autoantibodies against beta1 and AT(1)-receptor might play important roles in the pathogenesis of type 2 diabetes patients with hypertension and enlarged left ventricle.</p>

The relation between positive rate of autoantibodies against beta1 and M2-adrenergic receptors and urinary albumin excretion rate in the type 2 diabetes mellitus with refractory hypertension / 中华心血管病杂志

<p><b>OBJECTIVE</b>To explore the relation between the positive rates of autoantibodies against beta(1) adrenergic receptor (beta1-receptor)and (M2-receptor) with urinary albumin excretion rate (UAER) in type 2 diabetes patients with refractory hypertension.</p><p><b>METHODS</b>Autoantibodies against beta(1)- and M(2)-receptor as well as autoantibodies were determined in type 2 diabetes patients with (n = 136) or without (n = 111) refractory hypertension, hypertensive patients without renal failure (n = 60) and healthy control subjects (n = 40, control) by ELISA.</p><p><b>RESULTS</b>The positive rates of the autoantibodies against beta1-receptors (44.9%) and M(2)-receptor (37.5%) in patients with type 2 diabetes with refractory hypertension were significantly higher than those in patients with type 2 diabetes without refractory hypertension (27.9% and 24.3%, respectively, all P < 0.05), in patients with hypertension without renal failure (11.7% and 15.0%, all P < 0.01) and in healthy controls (8.3% and 7.5%, all P < 0.01). In type 2 diabetes patients with refractory hypertension and renal failure (UAER > or = 200 microg/min), the positive rates of the autoantibodies against beta(1)-receptor (87.1%, 27/31) and against M(2)-receptor (67.7%, 21/31) were significantly higher than those in type 2 diabetes patients with refractory hypertension but without renal failure (UAER 20 - 199 microg /min, 46.7%, 28/60 and 41.7%, 25/60, respectively, all P < 0.05).</p><p><b>CONCLUSION</b>The serum beta(1)- and M (2)-receptor autoantibodies are positively associated with the UAER level and suggest that these autoantibodies against beta(1) and M(2)-receptor may play important roles in the pathogenesis of the type 2 diabetes with refractory hypertension.</p>

Autoantibodies against beta1 and M2 receptor in diabetic patients with refractory hypertension / 中华心血管病杂志

<p><b>OBJECTIVE</b>To explore the role of the autoantibodies against M(2)-muscarinic receptor (M(2)-receptor), beta(1)-adrenergic receptor (beta(1)-receptor) in the development of diabetic with refractory hypertension.</p><p><b>METHODS</b>Serum autoantibodies against M(2) and beta(1) were detected by ELISA using synthesized epitopes of the second extracellular loop of M(2) receptor (169 - 193) and beta(1) receptor (197 - 222) in healthy controls (n = 40), diabetic patients (n = 62), diabetic patients with non-refractory hypertension (n = 55) and diabetic patients with refractory hypertension (n = 81).</p><p><b>RESULTS</b>The positive rates of the autoantibodies against M(2) receptor and beta(1) receptor were similar among healthy controls (15.0% and 17. 5%), diabetes mellitus patients (17.7% and 14.5%) and diabetic patients with non-refractory hypertension (16.4% and 12.7%) but are significantly higher in diabetic patients with refractory hypertension (64.2% and 55.6%, P < 0.01 vs. other 3 groups).</p><p><b>CONCLUSION</b>This finding suggests that autoimmune mechanisms might play a role in the pathogenesis of diabetic patients with refractory hypertension.</p>

Association of T-786C polymorphisms of eNOS gene with diabetic nephropathy / 中华内分泌代谢杂志

PCR/ASO probes were applied to analyse the T-786C polymorphisms in 5′-flanking region of endothelial nitric oxide synthase(eNOS)gene in type 2 diabetic patients with or without nephropatby and healthy individuals.The results showed that the T-786C polymorphisms of eNOS gene seemed to be related to diabetic nephropathy in type 2 diabetes.

Relationship between plasma osteoprotegerin and endothelium-dependent arterial dilation in type 2 diabetic patients / 中华内分泌代谢杂志

Objective To research the relationship between plasma osteoprotegerin (OPG) level and endothelium-dependent arterial dilation (EDAD) in type 2 diabetic patients.Methods The subjects included 40 newly diagnosed type 2 diabetic patients and 46 healthy subjects.Insulin therapy were then given to all diabetic patients for 6 months.Plasma OPG was measured by a sandwich ELISA method,and brachial artery diameter was determined by high resolution ultrasound at rest after reactive hyperemia and after sublingual glyceryl trinitrate (GTN).Results Plasma OPG level in diabetic patients before treatment was (3.44?0.52) ng/L,which was significantly higher than that in control (2.38?0.25 ) ng/L (P

Protective effect of vitamin C on endothelium-dependent arterial dilation in patients with impaired glucose tolerance during oral glucose loading / 中华内分泌代谢杂志

During oral glucose tolerance test(OGTT),endothelium-dependent vasodilation(EDD)at different time points in impaired glucose tolerance(IGT)group was lower than that in normal control group.EDD at 60 and 120 min in IGT + vitamin C group was higher than that in IGT group(all P＜0.05).There was a negative relationship between blood glucose level and EDD during OGTT in IGT patients.

A survey of metabolic syndrome and its related risk factors among middle and elderly aged permanent inhabitants in Wuhan / 中华内分泌代谢杂志

A cross-sectional survey with multiple-stage and random sampling was performed among middle and elderly aged permanent inhabitants in Wuhan area.The prevalences of metabolic syndrome,diabetes mellitus, impaired glucose tolerance,hypertension and obesity were 12.2%,11.8%,10.3%,31.9% and 48.0% respectively.