Effect of glucagon-like peptide 1 receptor agonists on body fat redistribution and muscle mass in overweight and obese type 2 diabetic patients / 南方医科大学学报

OBJECTIVE@#To investigate the effect of glucagon-like peptide 1 receptor agonists (GLP-1RAs) on body fat redistribution and muscle mass in overweight/obese patients with type 2 diabetes (T2DM).@*METHODS@#We retrospectively analyzed the data of 76 patients with body mass indexes (BMI)≥24 kg/m, who had an established diagnosis of T2DM in our department between December, 2014 and September, 2015. We divided these patients according to their BMI in overweight group (BMI of 24-27.9 kg/m, =14), obese group (BMI of 28-31.9 kg/m, =35) and severely obese group (BMI≥32 kg/m, =27). All the patients received treatment with GLP-1RAs (Exenatide or Liraglutide) for 3.0 to 29.0 weeks (mean 8.9 weeks), and their blood glucose, HbA1c and serum lipids were analyzed. For each patient, the fat and muscle masses were analyzed using a human body composition analyzer (JAWON-IOI353, Korea) before and after GLP-1RAs treatment.@*RESULTS@#Treatment with GLP-1RAs significantly decreased BMI and visceral adiposity index (VAI) in all the patients in the 3 groups ( < 0.05). The treatment significantly decreased the body weight in the overweight group and obese group by 2.70 kg (0.60-4.95 kg) and 2.65 kg (1.45-6.40 kg), respectively ( < 0.05), and significantly decreased the waist-to-hip ratio (WHR) in the overweight group ( < 0.05). The obese and severely obese patients showed significantly decreased percentage body fat (including both subcutaneous and visceral fat) and increased muscle mass after the treatment ( < 0.05). Compared with those in the overweight group, the percentage body fat and VAI were significantly decreased in the obese group after the treatment ( < 0.05), and the percentage of subcutaneous fat reduced and the muscle ratio increased more obviously in the obese and severely obese patients ( < 0.05).@*CONCLUSIONS@#GLP-1RAs treatment can significantly lower BMI and improve body fat distribution in obese patients with T2DM, especially in patients with a greater BMI.

Exendin-4 alleviates oxidative stress and liver fibrosis by activating Nrf2/HO-1 in streptozotocin-induced diabetic mice / 南方医科大学学报

OBJECTIVE@#To investigate the effects of exendin-4 on hepatic lipid metabolism, fibrosis and oxidative stress in mice with streptozotocin (STZ)-induced diabetes and explore the underlying mechanisms.@*METHODS@#C57BL/6J mice were fed with high-fat diet (HFD) for 4 weeks and received intraperitoneal injections of 120 mg/kg STZ to induce diabetes. After successful modeling, the mice were randomized into diabetic control group and exendin-4 treatment group (DM+E4), and in the latter group, the mice were given a daily dose of 1 nmol/kg of exendin-4 for 8 weeks. The changes in the body weight (BW) and random blood glucose (RBG) in the mice were recorded. The mRNA expressions of the genes related with liver lipid metabolism, fibrosis and oxidative stress were analyzed using RT-PCR, and the structural changes of the liver tissues were observed with HE, Sirius red and oil red O staining; the expressions of TGF-β1, Nrf2 and HO-1 proteins in the liver tissues were detected using Western blotting.@*RESULTS@#The diabetic mice showed significantly higher RBG levels and BW with obvious lipid deposition, fibrosis and oxidative stress in the liver as compared with the normal control mice ( < 0.001). Exendin-4 treatment of the diabetic mice did not significantly lessened liver lipid deposition but obviously reduced the levels of RBG and TG ( < 0.05), lowered the expression levels of liver fibrosis-related genes TGF-β, -SMA and Col-Ⅰ ( < 0.05), increased the expression levels of the antioxidant genes Nrf2, HO-1 and GPX4 ( < 0.01), and enhanced the protein expressions of Nrf2 and HO-1 in the liver tissues ( < 0.01).@*CONCLUSIONS@#Exendin-4 improves liver fibrosis and oxidative stress in diabetic mice by activating Nrf2/HO-1 pathway without significantly reducing liver lipid deposition.

Effect of DPP4 inhibitor sitagliptin on expressions of early growth response-1 and fibronectin in the kidney of ApoE gene knockout mice / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effects of the DPP4 inhibitor sitagliptin on the expressions of early growth response-1 (Egr-1) and fibronectin in the kidney of ApoE gene knockout mice.</p><p><b>METHODS</b>Eight-week-old male ApoE gene knockout mice were randomly divided into sitagliptin + apoE(-/-) group and apoE(-/-) group (n=6), with 6 C57BL mice as the normal control group. After feeding with high-fat diet and drug treatment for 16 weeks, the mice underwent intraperitoneal glucose tolerance test (IPGTT) and were measured for 24-h urinary albumin using ELISA. All the mice were then sacrificed to examine the changes of blood lipid profile and for detection of Egr-1 and fibronectin mRNA and proteins in the renal tissue using real-time PCR and Western blotting.</p><p><b>RESULTS</b>The mice in both apoE(-/-) group and sitagliptin+apoE(-/-) group all showed prominently increased blood lipids as compared with the control group (P<0.05) without significant differences between the two apoE(-/-) groups. The level of HDL was significantly higher in sitagliptin +apoE(-/-) group than in apoE(-/-) group (P<0.001) and control group (P<0.001). IPGTT showed no significant differences in the levels of blood glucose among the 3 groups. The excretion of urinary albumin was increased in apoE(-/-) group compared with the control group (P<0.01), but was significantly lower in sitagliptin+ apoE(-/-) group than in apoE(-/-) group (P<0.01). Real-time PCR and Western blotting showed significantly decreased mRNA and protein expressions of renal cortical Egr-1 and fibronectin in sitagliptin+apoE(-/-) group compared with apoE(-/-) group.</p><p><b>CONCLUSION</b>Sitagliptin can reduce the renal expression of fibronectin by regulating the expression of Egr-1 to achieve renal protection.</p>

Risk factors for diabetic kidney diseases in inpatients with type 2 diabetes / 中华内分泌代谢杂志

Objective To analyze risk factors for diabetic kidney disease (DKD) in inpatients with type 2 diabetes.Methods A total of 930 inpatients with type 2 diabetes were enrolled in the study and grouped according to different levels of estimated glomerular filtration rate (eGFR),albuminuria,and diabetic retinopathy.Logistic regression analysis was adopted to explore the risk factors for DKD in inpatients with type 2 diabetes.Results (1) The prevalence of albuminuria in patients with type 2 diabetes mellitus was increased with declining eGFR (P ＜ 0.05).(2) The prevalences of DKD and non-diabetic renal disease (NDRD) in patients with type 2 diabetes mellitus were 22.26％ and 8.92％,respectively.Compared with patients with NDRD,patients with DKD had longer diabetic duration,higher levels of systolic blood pressure,serum creatinine,and urinary albumin excretion,and lower levels of hemoglobin[(125.40 ± 21.95 vs 138.18 ± 19.67) g/L],serum albumin[(37.45 ± 5.54 vs 40.55 ± 3.55) g/L],and eGFR[(89.66 (59.10-108.25) vs 103.15 (85.39-114.88) ml · min-1 · (1.73 m2)-1,all P＜0.05].(3) Logistic regression analysis showed that age,diabetic duration,systolic blood pressure,serum uric acid,diabetic retinopathy,and hypertension are the independent risk factors for diabetic kidney disease in inpatients with type 2 diabetes,while serum albumin was the protective factor (all P＜0.01).Conclusions A variety of clinic risk factors were associated with DKD.Better control of blood pressure,serum uric acid,and hypoalbuminemia should be performed to delay the progress of DKD.

Effects of metformin on apoptosis induced by advanced glycation end-products and expressions of caspase-3, Bax and Bcl-2 in human dermal fibroblasts in vitro / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of metformin in protecting against advanced glycation end products (AGEs)-induced apoptosis in human primary dermal fibroblasts.</p><p><b>METHODS</b>Fibroblasts were exposed to 100, 200, or 300 µg/mL AGEs, 300 µg/mL bovine serum albumin (BSA), or 300 µg/mL AGEs and 1 mmol/L metformin for 24, 48, or 72 h. The exposed cells were examined for cell apoptosis using a cell counting kit. The expressions of caspase-3, Bax and Bcl-2 protein in the fibroblasts treated for 72 h were detected with Western blotting.</p><p><b>RESULTS</b>AGEs exposures caused significant dose- and time-dependent apoptosis in the fibroblasts. A 72-h exposure to 300 µg/mL AGEs resulted in obviously increased apoptosis of the fibroblasts compared to the control group (0.72 ± 0.02 vs 1 ± 0.04, P<0.05), and metformin significantly decreased AGEs-induced apoptosis (0.98 ± 0.02 vs 0.72 ± 0.02, P<0.05). The expressions of caspase-3 and Bax protein were significantly increased (P<0.05) and Bcl-2 protein expression was decreased (P<0.05) with a lowered Bcl-2/Bax ratio in AGEs-treated fibroblasts (P<0.05), and such changes were significantly reversed by metformin treatment (P<0.05).</p><p><b>CONCLUSION</b>Metformin can antagonize AGEs-induced apoptosis in human dermal fibroblasts by regulating the expressions of caspase-3, Bax and Bcl-2.</p>