Role of Canagliflozin on function of CD34+ve endothelial progenitor cells (EPC) in patients with type 2 diabetes.
Role of Canagliflozin on function of CD34+ve endothelial progenitor cells (EPC) in patients with type 2 diabetes.
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DOI：
10.1186/s12933-021-01235-4
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发表时间：
2021-02-13
影响因子：
9.3
通讯作者：
Sen S
中科院分区：
文献类型：
--
作者：
Nandula SR;Kundu N;Awal HB;Brichacek B;Fakhri M;Aimalla N;Elzarki A;Amdur RL;Sen S
内皮祖细胞（EPC）在2型糖尿病（T2DM）和慢性肾脏疾病（CKD）中均表现出功能障碍，导致内皮和肾脏灌注的再生不良。细胞生物标志物（例如CD34+VE祖细胞）上的ZIN（CG），可能帮助预测CVD风险，在患有CKD的T2DM患者中尚未探索。
这是一项初步研究，其中29名接受二甲双胍和/或胰岛素的受试者在16周，双盲，随机的安慰剂匹配试验中，与匹配的安慰剂相比，剂量低100 mg cg，作为干预组，与匹配具有血管参数例如，在第0、8和16周收集了与心脏代谢健康有关的动脉刚度，与心脏代谢健康有关的血清生物化学，静息能量消耗和身体组成。
与安慰剂组相比，在CG治疗组中观察到CD34+VE细胞迁移功能的CXCR4受体的显着表达。重要的在CG组中观察到葡萄糖和HBA1C水平的降低以及脂肪素的收缩压和舒张压的降低（p = 0.006）。
低剂量的canagliflozin对2型糖尿病中的CD34+细胞功能，血清生物化学和尿足细胞特异性外泌体具有有益的作用。
Endothelial progenitor cells (EPCs) has been shown to be dysfunctional in both type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) leading to poor regeneration of endothelium and renal perfusion. EPCs have been shown to be a robust cardiovascular disease (CVD) risk indicator. Effect of sodium glucose channel inhibitors (SGLT2i) such as Canagliflozin (CG) on a cellular biomarker such as CD34+ve progenitor cells, which may help predict CVD risk, in patients with T2DM with established CKD has not been explored. This is a pilot study where 29 subjects taking metformin and/or Insulin were enrolled in a 16 week, double blind, randomized placebo matched trial, with a low dose 100 mg CG as the intervention group compared to matched placebo. Type 2 diabetes subjects (30–70 years old), with hemoglobin A1c (HbA1c) of 7–10%, were enrolled. CD34+ve cell number, migratory function, gene expression along with vascular parameters such as arterial stiffness, serum biochemistry pertaining to cardio-metabolic health, resting energy expenditure and body composition were measured. Data were collected at week 0, 8 and 16. A mixed model regression analysis was done and p value less than 0.05 was considered statistically significant. A significant expression of CXCR4 receptor with a concomittant increase in migratory function of CD34+ve cells was observed in CG treated group as compared to placebo group. Gene expression analysis of CD34+ve cells showed an increase in expression of antioxidants (superoxide dismutase 2 or SOD2, Catalase and Glutathione Peroxidase or GPX) and notable endothelial markers (PECAM1, VEGF-A, and NOS3). A significant reduction in glucose and HbA1c levels were observed along with improved systolic and diastolic blood pressure in the CG group. A significant increase in adiponectin (p = 0.006) was also noted in treatment group. Urinary exosomal protein leak in urine, examining podocyte health (podocalyxin, Wilm’s tumor and nephrin) showed reduction with CG Low dose Canagliflozin has a beneficial effect on CD34+ cell function, serum biochemistry and urinary podocyte specific exosomes in type 2 diabetes.
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影响因子：
6
作者：
Medina RJ;Barber CL;Sabatier F;Dignat-George F;Melero-Martin JM;Khosrotehrani K;Ohneda O;Randi AM;Chan JKY;Yamaguchi T;Van Hinsbergh VWM;Yoder MC;Stitt AW
通讯作者：
Stitt AW
影响因子：
4.6
作者：
Azevedo RSS;de Sousa JR;Araujo MTF;Martins Filho AJ;de Alcantara BN;Araujo FMC;Queiroz MGL;Cruz ACR;Vasconcelos BHB;Chiang JO;Martins LC;Casseb LMN;da Silva EV;Carvalho VL;Vasconcelos BCB;Rodrigues SG;Oliveira CS;Quaresma JAS;Vasconcelos PFC
通讯作者：
Vasconcelos PFC
影响因子：
13.2
作者：
Perlman, RL;Finkelstein, FO;Saran, R
通讯作者：
Saran, R
影响因子：
37.8
作者：
Neuen BL;Ohkuma T;Neal B;Matthews DR;de Zeeuw D;Mahaffey KW;Fulcher G;Desai M;Li Q;Deng H;Rosenthal N;Jardine MJ;Bakris G;Perkovic V
通讯作者：
Perkovic V
影响因子：
2.6
作者：
Amorim, Rayne Gomes;Guedes, Glaucevane da Silva;Santos, Juliana Célia de Farias
通讯作者：
Santos, Juliana Célia de Farias