Related Experiment Video

Updated: Aug 10, 2025

Identification of the Source of Secreted Proteins in the Kidney by Brefeldin A Injection
10:15

Identification of the Source of Secreted Proteins in the Kidney by Brefeldin A Injection

Published on: November 10, 2021

1.9K

Gliflozins Have an Anti-Inflammatory Effect on Renal Proximal Tubular Epithelial Cells in a Diabetic and Inflammatory

Benjamin Koch1, Dominik C Fuhrmann2, Ralf Schubert3

  • 1Department of Internal Medicine 4, Nephrology, University Hospital, Goethe-University, 60596 Frankfurt, Germany.

International Journal of Molecular Sciences
|February 11, 2023
PubMed

Insights

Sodium-glucose cotransporter 2 (SGLT-2) inhibitors like empagliflozin and dapagliflozin reduce inflammation in kidney cells. These gliflozins significantly decrease ICAM-1 protein expression, suggesting a novel anti-inflammatory role in diabetic kidney disease.

Area of Science:

  • Nephrology
  • Pharmacology
  • Cell Biology

Background:

  • Diabetic kidney disease (DKD) pathogenesis involves inflammation.
  • Sodium-glucose cotransporter 2 (SGLT-2) inhibitors (gliflozins) reduce DKD progression.
  • Gliflozins primarily inhibit renal glucose reabsorption.

Purpose of the Study:

  • To investigate the anti-inflammatory effects of SGLT-2 inhibition in human renal proximal tubular epithelial cells (PTCs).
  • To assess the impact of empagliflozin and dapagliflozin on pro-inflammatory factors in a diabetic milieu.
  • To evaluate the influence of gliflozins on Intercellular Adhesion Molecule-1 (ICAM-1) expression.

Main Methods:

  • Utilized highly purified human renal proximal tubular epithelial cells (PTCs) as an in vitro model.
  • Exposed PTCs to a high glucose (diabetic) and cytokine (inflammatory) microenvironment.
  • Quantified the expression of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, MCP-1) and ICAM-1 mRNA and protein.

Main Results:

  • Both empagliflozin and dapagliflozin demonstrated anti-inflammatory effects.
  • Induced expression of four cytokines was only slightly attenuated.
  • Significantly reduced ICAM-1 mRNA expression by ~13.5% with empagliflozin.
  • Significantly inhibited ICAM-1 protein expression from 24.71 ± 1.0 ng/mL to 18.81 ± 3.9 ng/mL (empagliflozin) and 19.62 ± 2.1 ng/mL (dapagliflozin).

Conclusions:

  • Empagliflozin and dapagliflozin exhibit an additional anti-inflammatory effect in primary human PTCs.
  • This effect was observed at therapeutically relevant concentrations.
  • SGLT-2 inhibition may offer benefits beyond glucose control in managing diabetic kidney disease.
Keywords:
ICAM-1cytokinesdapagliflozinempagliflozinepithelial cellsinflammationkidneyproximal tubulerenal tubular cells

More Related Videos

Characterization of a Novel Human Organotypic Retinal Culture Technique05:51

Characterization of a Novel Human Organotypic Retinal Culture Technique

Published on: June 9, 2021

4.1K
Assessment of Kidney Function in Mouse Models of Glomerular Disease09:16

Assessment of Kidney Function in Mouse Models of Glomerular Disease

Published on: June 30, 2018

17.8K

Related Concept Videos

Dipeptidyl Peptidase 4 Inhibitors01:23

Dipeptidyl Peptidase 4 Inhibitors

Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a...
224
Oral Hypoglycemic Agents: Biguanides and Glitazones01:26

Oral Hypoglycemic Agents: Biguanides and Glitazones

Biguanides, particularly metformin (Glucophage), are insulin sensitizers that enhance glucose uptake, thereby reducing insulin resistance. Unlike sulfonylureas, metformin doesn't prompt insulin secretion, which helps to curb hypoglycemia risk. Metformin is beneficial in treating conditions like polycystic ovary syndrome due to its insulin-resistance reduction capability. The drug's primary action involves curtailing hepatic gluconeogenesis, a significant contributor to high blood...
252
Oral Hypoglycemic Agents: Glinides01:06

Oral Hypoglycemic Agents: Glinides

Repaglinide (Prandin) and Nateglinide (Starlix), known as glinides, are oral insulin secretagogues that stimulate insulin release from pancreatic β cells by closing the ATP-sensitive potassium channels (KATP channel). Repaglinide controls insulin release from pancreatic β cells by managing potassium efflux. It shares two binding sites with sulfonylureas and also has a unique site, indicating overlapping mechanisms of action. With a rapid onset and a 4-7 hour duration, it effectively...
203
Glucagon-like Receptor Agonists01:24

Glucagon-like Receptor Agonists

Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
380