Objective:To evaluate the effect of canagliflozin on intrarenal fat content and oxygenation in newly-diagnosed type 2 diabetes patients.Methods:Twenty-three newly-diagnosed type 2 diabetes patients were divided into canagliflozin( n=11) and glimepiride control( n=12) groups .Both groups received MRI scanning with Dixon MRI and BOLD MRI sequence to assess patients′ intrarenal fat content, oxygenation level before treatment and 24 weeks after treatment. Fasting blood glucose, glycosylated hemoglobin, blood uric acid, blood lipids, blood pressure, weight, and other metabolic index were also tested before and after treatment. Furthermore, the relationship between body mass index(BMI) and intrarenal fat content and the correlation between changes in intrarenal fat content and improvement in renal hypoxia were analyzed. Results:No significant differences were found in baseline age, body weight, fasting blood glucose, glycosylated hemoglobin, blood lipid, and serum uric acid between the two groups. There was no significant difference in fasting blood glucose, glycosylated hemoglobin, cholesterol(CHO), low-density lipoprotein-cholesterol(LDL-C), and triglycerides(TG) levels in both groups after 12 and 24 weeks of treatment. The decrease in body weight, blood uric acid level, and diastolic blood pressure from baseline in the canagliflozin group was greater than those in the control group( P<0.05). Two groups of patients with type 2 diabetes at baseline had no obvious difference in intrarenal fat content, and the patients′ BMI showed no obvious correlation with degree of intrarenal fat accumulation. Canagliflozin treatment for 24 weeks could reduce intrarenal fat content, which was higher than that of control group. The R2 * values of renal cortex and medulla in the canagliflozin group decreased from baseline by 19.22% and 22.63% respectively( P<0.05), whereas no significant difference was seen in the glimepiride control group. The decrease of intrarenal fat content in the canagliflozin group was related to the improvement of renal cortex and medulla oxygenation. Conclusion:Canagliflozin can reduce intrarenal fat accumulation and improve renal cortical hypoxia in newly diagnosed type 2 diabetes patients with normal renal function.

Objective To observe the effect of Krüppel-like factor 4(KLF4)on cholesterol deposition in macrophages treated with high glucose,and to explore the mechanism related to macrophage autophagy.Methods Ten Balb/c mice were randomly divided into the normal control(NC,n=5)group and the DM group(n=5).A diabetic mouse model was established,and the expression level of KLF4 protein in aorta was detected after high fat diet.After induction of THP-1 monocytes into macrophages,they were divided into the LV-NC group,the LV-KLF4 group,the si-NC group and the si-KLF4 group.Changes of cholesterol content,cell apoptosis and the expression level of autophagy related proteins and AKT/mTOR signaling pathway related proteins in THP-1 macrophages were observed after overexpression or knockout of KLF4.Results The expression level of KLF4 protein in aorta of diabetic mice was lower in the DM group than that of the NC group(P＜0.05).Meanwhile,under high glucose concentration,overexpression of KLF4 in THP-1 macrophages significantly decreased cholesterol deposition,cell apoptosis and P62 expression,increased Beclin1 expression,LC3 fluorescence intensity and also inhibited AKT/mTOR signaling pathway related protein expression(P＜0.05).After knocking down KLF4 expression,the results were reversed.Conclusion KLF4 alleviates cholesterol deposition in THP-1 macrophages by promoting autophagy under high glucose concentration.