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Abstract: FR-PO358

Expression Profiles of Glucose Transporters Along the Nephron in Non-Diabetic and Diabetic Kidneys

Session Information

Category: Diabetic Kidney Disease

  • 701 Diabetic Kidney Disease: Basic

Authors

  • Cheng, Charley, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States
  • Wei, Jin, Boston University School of Medicine, Boston, Massachusetts, United States
  • Zhang, Jie, Boston University School of Medicine, Boston, Massachusetts, United States
Background

In non-diabetic kidneys, over 99% of filtered glucose is reabsorbed in the proximal tubule (PT), resulting in limited delivery to the distal nephron. However, in diabetic kidneys, the excessive filtration of glucose surpasses the reabsorption capacity of the PT, leading to its presence in the distal nephron. This may trigger adaptations in the distal nephron to compensate for glucose reabsorption and minimize its excretion in urine. Despite extensive research, the comprehensive expression profiles of glucose transporters along the nephron remains incompletely understood. Hence, this study aims to identify the specific glucose transporters expressed in each tubule segment and investigate alterations in their expression in diabetes.

Methods

We identified glucose transporters expressed in distinct segments of the nephron and compared their gene expression between db/m and db/db mice by analyzing the snRNA-seq data (GEO: GSE184652). Additionally, we conducted microdissection of individual nephron segments from db/m and db/db mice and measured the gene expression of glucose transporters in these isolated tubular segments using RT-PCR and qPCR. To further validate the protein expression of these glucose transporters, we performed immunofluorescence (IF) staining and Western blot (WB) assays on whole kidneys.

Results

We unveiled the expression profiles of glucose transporters in specific segments of the nephron. Specifically, Slc2a4 (GLUT4) is expressed in thick ascending limb (TAL), distal convoluted tubule (DNT), connecting tubule (CNT), and intercalated cells (IC), and Slc2a1 (GLUT1) is expressed in TAL, macula densa, DCT, CNT, pricipal cells, and IC. Furthermore, our analysis revealed an upregulation of Slc2a4 expression in the TAL (27.96%), DCT (6.10%), CNT (53.95%), and IC (6.03%) and a downregulation of Slc2a1 expression in the DCT (-50.98%), CNT (-49.05%), and IC (-10.36%) in db/db mice compared to db/m mice. Additionally, we confirmed these findings through RT-PCR and qPCR in isolated tubular segments, as well as IF staining and WB assays in whole kidneys.

Conclusion

In this study, we identified glucose transporters expressed along the nephron and compared their expression levels in db/m and db/db mice. Notably, the glucose transporter GLUT4 in the distal nephron segments appears to play a significant role in compensating for glucose reabsorption in diabetes.

Funding

  • NIDDK Support