Role of Canagliflozin on function of CD34+ve endothelial progenitor cells (EPC) in patients with type 2 diabetes

Figures

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  Fig. 1. A significant difference in mean systolic blood pressure (a) and diastolic blood pressure (b) is observed between Canagliflozin and placebo groups. In Canagliflozin group both decreased from visit 1 to 2 and increased by visit 3. Whereas in placebo group both increased from visit 1 to 2 and decreased by visit 3. c HbA1c went down substantially in Canagliflozin group whereas it increased in Placebo group. The sharp decrease in HbA1c is seen in visit 1to visit 2 (p = 0.0919) and is stabilized from visit 2 to visit 3 in Canagliflozin group. d Glucose levels also followed the same trend as HbA1c in Canagliflozin group by sharp decrease from visit 1 to 2 and then stabilized till visit 3. Whereas, in placebo group glucose levels increased from visit 1 to 3. e A significant rise in adiponectin levels is noted in Canagliflozin group where as a sharp decrease is observed in placebo group from visit 2 to 3. f Inflammatory marker serum IL6 levels decreased. The difference was significant from visit 2 to 3 (p = 0.0259) in Canagliflozin group as compared to placebo group

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  Fig. 2. Migration Assay in response to SDF1alpha at 10 ng/ml concentration and gene expression of SDF1a receptor, CXCR-4 on CD34+ve cells. a Mean migration of CD34+ve cells towards SDF1-α (at 10 ng/ml) increased from visit 1 to 3 in Canagliflozin group as compared to placebo group (for visit 1 to 3 p = 0.03 and for visit 2–3 p = 0.05). b CXCR4 gene expression on CD34 positive cells is increased (p = 0.06) in Canagliflozin group as compared to placebo group at visit 3

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  Fig. 3. The effect of Canagliflozin on CD34+ve cell antioxidants gene expression. Fold change in gene expression of antioxidants SOD2 (a) in CD34+ve cells are increased in Canagliflozin group from visit 1 to 3. However, the same for the placebo group is decreased. Whereas the antioxidants, b Catalase (CAT) and c GPX3 gene expression increased in CD34+ve cells in Canagliflozin group from visit 2 to 3. However, the same for the placebo group is decreased. Overall, all the antioxidant genes showed increased expression going from visit 2 to visit 3, whereas the placebo there was a downward trend with catalase expression reaching statistical difference, overall

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  Fig. 4. The effect of Canagliflozin on CD34+ve cell Endothelial markers gene expression. Fold change in gene expression of Endothelial markers a VEGF-A, b KDR and c PECAM and endothelial function marker d NOS3 on CD34+ve cells increased significantly in Canagliflozin group from visit 1 to 3. However, the same for the placebo group is decreased. Gene expression is normalized to 18S

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  Fig. 5. Urinary exosome markers a Wilm’s tumor-1 (WT-1), b Nephrin and c Podocalyxin (PODXL) were identified by Western blot and followed by quantification. A trend in reduced mean band intensities for Urinary exosome markers are observed in Canagliflozin group from visit 1 to visit 3 as compared to placebo group