Complex Positive Effects of SGLT-2 Inhibitor Empagliflozin in the Liver, Kidney and Adipose Tissue of Hereditary Hypertriglyceridemic Rats: Possible Contribution of Attenuation of Cell Senescence and Oxidative Stress

Trnovská, Jaroslava; Svoboda, Petr; Kuzma, Marek; Kratochvílová, Helena; Kasperová, Barbora Judita; Dvorakova, Iveta; Rosolova, Katerina; Malínská, Hana; Hüttl, Martina; Marková, Irena; Oliyarnyk, Olena; Melčová, Magdalena; Škop, Vojtěch; Mráz, Miloš; Hubáčková, Soňa; Haluzı́k, Martin

doi:10.3390/ijms221910606

Cited by 18 publications

(10 citation statements)

References 81 publications

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“…This phenomenon has been described in the literature as a result of increased hepatic gluconeogenesis or increase endogenous glucagon production described in diabetic patients. [21][22][23] The exact mechanism responsible for this effect of empagliflozin is not completely elucidated. We consider that in a clinical setting it generally is overlooked because emergence of glycosuria.…”

Section: Discussionmentioning

confidence: 99%

Blockade of sodium–glucose co-transporters improves peritoneal ultrafiltration in uraemic rodent models

et al. 2023

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Background: The most used PD fluids contain glucose as a primary osmotic agent. Glucose peritoneal absorption during dwell decreases the osmotic gradient of peritoneal fluids and causes undesirable metabolic consequences. Inhibitors of sodium–glucose co-transporter (SGLT) type 2 are wildly used for the treatment of diabetes, heart and kidney failure. Previous attempts to use SGLT2 blockers in experimental peritoneal dialysis yielded contrasting results. We studied whether peritoneal SGLTs blockade may improve ultrafiltration (UF) via partial inhibition of glucose uptake from dialysis fluids. Methods: Kidney failure was induced in mice and rats by bilateral ureteral ligation, and dwell was performed by injection of glucose-containing dialysis fluids. The effect of SGLT inhibitors on glucose absorption during fluid dwell and UF was measured in vivo. Results: Diffusion of glucose from dialysis fluid into the blood appeared to be sodium-dependent, and blockade of SGLTs by phlorizin and sotagliflozin attenuated blood glucose increment thereby decreasing fluid absorption. Specific SGLT2 inhibitors failed to reduce glucose and fluid absorption from the peritoneal cavity in a rodent kidney failure model. Conclusions: Our study suggests that peritoneal non-type 2 SGLTs facilitate glucose diffusion from dialysis solutions, and we propose that limiting glucose reabsorption by specific SGLT inhibitors may emerge as a novel strategy in PD treatment to enhance UF and mitigate the deleterious effects of hyperglycaemia.

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Section: Discussionmentioning

confidence: 99%

Blockade of sodium–glucose co-transporters improves peritoneal ultrafiltration in uraemic rodent models

et al. 2023

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“…In a different model, empagliflozin accelerated the regression of atherosclerosis [ 76 ]. Lowered triglycerides content and an increase in HDL cholesterol were also found in hypertriglyceridemic mice [ 77 ].…”

Section: Vascular Effects and Inflammationmentioning

confidence: 99%

Sodium Glucose Cotransporter-2 Inhibitors: Spotlight on Favorable Effects on Clinical Outcomes beyond Diabetes

Chábová

Zakiyanov

2022

IJMS

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Sodium glucose transporter type 2 (SGLT2) molecules are found in proximal tubules of the kidney, and perhaps in the brain or intestine, but rarely in any other tissue. However, their inhibitors, intended to improve diabetes compensation, have many more beneficial effects. They improve kidney and cardiovascular outcomes and decrease mortality. These benefits are not limited to diabetics but were also found in non-diabetic individuals. The pathophysiological pathways underlying the treatment success have been investigated in both clinical and experimental studies. There have been numerous excellent reviews, but these were mostly restricted to limited aspects of the knowledge. The aim of this review is to summarize the known experimental and clinical evidence of SGLT2 inhibitors’ effects on individual organs (kidney, heart, liver, etc.), as well as the systemic changes that lead to an improvement in clinical outcomes.

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“…In metabolism, SGLT2i can improve the metabolism of animal models [ 31 ] and increase gluconeogenesis [ 32 ], possibly by inducing the expression of the key rate-limiting enzyme of gluconeogenesis [ 33 ]. In some animal models, SGLT2i can inhibit renal gluconeogenesis ( Table 1 ) [ 34 , 35 ].…”

Section: Sglt2i Provide Renal Protection In Animal Modelsmentioning

confidence: 99%

Signaling Pathways of Podocyte Injury in Diabetic Kidney Disease and the Effect of Sodium-Glucose Cotransporter 2 Inhibitors

Chen

Wang

Lin

et al. 2022

Cells

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Diabetic kidney disease (DKD) is one of the most important comorbidities for patients with diabetes, and its incidence has exceeded one tenth, with an increasing trend. Studies have shown that diabetes is associated with a decrease in the number of podocytes. Diabetes can induce apoptosis of podocytes through several apoptotic pathways or induce autophagy of podocytes through related pathways. At the same time, hyperglycemia can also directly lead to apoptosis of podocytes, and the related inflammatory reactions are all harmful to podocytes. Podocyte damage is often accompanied by the production of proteinuria and the progression of DKD. As a new therapeutic agent for diabetes, sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been demonstrated to be effective in the treatment of diabetes and the improvement of terminal outcomes in many rodent experiments and clinical studies. At the same time, SGLT2i can also play a protective role in diabetes-induced podocyte injury by improving the expression of nephrotic protein defects and inhibiting podocyte cytoskeletal remodeling. Some studies have also shown that SGLT2i can play a role in inhibiting the apoptosis and autophagy of cells. However, there is no relevant study that clearly indicates whether SGLT2i can also play a role in the above pathways in podocytes. This review mainly summarizes the damage to podocyte structure and function in DKD patients and related signaling pathways, as well as the possible protective mechanism of SGLT2i on podocyte function.

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Complex Positive Effects of SGLT-2 Inhibitor Empagliflozin in the Liver, Kidney and Adipose Tissue of Hereditary Hypertriglyceridemic Rats: Possible Contribution of Attenuation of Cell Senescence and Oxidative Stress

Cited by 18 publications

References 81 publications

Blockade of sodium–glucose co-transporters improves peritoneal ultrafiltration in uraemic rodent models

Blockade of sodium–glucose co-transporters improves peritoneal ultrafiltration in uraemic rodent models

Sodium Glucose Cotransporter-2 Inhibitors: Spotlight on Favorable Effects on Clinical Outcomes beyond Diabetes

Signaling Pathways of Podocyte Injury in Diabetic Kidney Disease and the Effect of Sodium-Glucose Cotransporter 2 Inhibitors

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