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Prompt apoptotic response to high glucose in SGLT-expressing renal cells.
- Source :
-
American journal of physiology. Renal physiology [Am J Physiol Renal Physiol] 2019 May 01; Vol. 316 (5), pp. F1078-F1089. Date of Electronic Publication: 2019 Mar 13. - Publication Year :
- 2019
-
Abstract
- It is generally believed that cells that are unable to downregulate glucose transport are particularly vulnerable to hyperglycemia. Yet, little is known about the relation between expression of glucose transporters and acute toxic effects of high glucose exposure. In the present ex vivo study of rat renal cells, we compared the apoptotic response to a moderate increase in glucose concentration. We studied cell types that commonly are targeted in diabetic kidney disease (DKD): proximal tubule cells, which express Na <superscript>+</superscript> -dependent glucose transporter (SGLT)2, mesangial cells, which express SGLT1, and podocytes, which lack SGLT and take up glucose via insulin-dependent glucose transporter 4. Proximal tubule cells and mesangial cells responded within 4-8 h of exposure to 15 mM glucose with translocation of the apoptotic protein Bax to mitochondria and an increased apoptotic index. SGLT downregulation and exposure to SGLT inhibitors abolished the apoptotic response. The onset of overt DKD generally coincides with the onset of albuminuria. Albumin had an additive effect on the apoptotic response. Ouabain, which interferes with the apoptotic onset, rescued from the apoptotic response. Insulin-supplemented podocytes remained resistant to 15 and 30 mM glucose for at least 24 h. Our study points to a previously unappreciated role of SGLT-dependent glucose uptake as a risk factor for diabetic complications and highlights the importance of therapeutic approaches that specifically target the different cell types in DKD.
- Subjects :
- Animals
Cells, Cultured
Diabetic Nephropathies pathology
Epithelial Cells metabolism
Epithelial Cells pathology
Insulin pharmacology
Kidney Tubules, Proximal metabolism
Kidney Tubules, Proximal pathology
Male
Mesangial Cells metabolism
Mesangial Cells pathology
Ouabain pharmacology
Podocytes metabolism
Podocytes pathology
Rats, Sprague-Dawley
Signal Transduction
Time Factors
Apoptosis drug effects
Diabetic Nephropathies metabolism
Epithelial Cells drug effects
Glucose toxicity
Kidney Tubules, Proximal drug effects
Mesangial Cells drug effects
Podocytes drug effects
Sodium-Glucose Transporter 1 metabolism
Sodium-Glucose Transporter 2 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1466
- Volume :
- 316
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Renal physiology
- Publication Type :
- Academic Journal
- Accession number :
- 30864838
- Full Text :
- https://doi.org/10.1152/ajprenal.00615.2018