ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on X

Kidney Week

ASN / Education & Meetings / Kidney Week /
Abstract: FR-PO616

The Impact of Glucagon-Like-Peptide-1on JAK-STAT Pathway in Diabetic Kidney Disease in db/db Mice and in Endothelial Cells Exposed to a Diabetic Environment

Session Information

Category: Diabetes

  • 501 Diabetes Mellitus and Obesity: Basic - Experimental

Authors

  • Einbinder, Yael, Meir Medical Center, Kfar Saba, Kfar Saba, Center, Israel
  • Benchetrit, Sydney, Meir Medical Center, Kfar Saba, Israel
Background

The Janus kinase/signal transducer and transcription activator (JAK/STAT) proteins mediate the actions of many cytokines, chemokines, hormones, and growth factors critical to cell proliferation, differentiation, migration, and apoptosis. This study used db/db mice and endothelial cells (EC) to determine the effect of a diabetic environment on the JAK-STAT pathway, and to assess the potential effect of GLP-1 analogue in both models.

Methods

C57BL/6 (WT) and BKS.Cg-Dock7m +/+ Leprdb/db (db/db) mice were randomized to WT group, db/db mice (diabetic control group) and db/db mice treated with GLP-1 analog (Liraglutide) for 14 weeks. The kidneys were then perfused and removed for mRNA, protein analysis and Immunohistochemistry. EC obtained from Human umbilical vein were stimulated with AGE-HSA, glucose and GLP-1 for 24 hours.

Results

p-STAT3 (Ser 727) and p-STAT3 (Tyr 705) were significantly up-regulated in control db/db mice compared to WT mice. GLP-1 analog significantly down-regulated p-STAT3 (Ser 727, Tyr 705) protein expression compared to control db/db mice. P-STAT3 was mainly expressed in the glomeruli, while p-JAK2 was expressed in the tubules also. In EC stimulated with diabetic environment p-STAT3 (Tyr 705) and JAK2 were up regulated while GLP-1 analog significantly down-regulated there expression. The GLP-1 analog inhibited the target gene SIRT1 in db/db mice and in EC culture.

Conclusion

JAK-STAT pathway is activated in experimental models of diabetes mellitus. The GLP-1 analogue (liraglutide) inhibited STAT3 and JAK2 expression in db/db mice and in EC culture possibly through inhibition of SIRT1.