Schmidt, Christoph and Hoecherl, Klaus and Bucher, Michael (2007) Regulation of renal glucose transporters during severe inflammation. AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 292 (2). F804-F811. ISSN 1931-857X, 1522-1466
Full text not available from this repository. (Request a copy)Abstract
Severe sepsis is accompanied by acute renal failure (ARF) with renal tubular dysfunction and glucosuria. In this study, we aimed to determine the regulation of renal tubular glucose transporters during severe experimental inflammation. Male C57BL/6J mice were injected with LPS or proinflammatory cytokines, and renal perfusion, glomerular filtration rate (GFR), fractional glucose excretion, and expression of tubular glucose transporters were determined. We found a decreased plasma glucose concentration with impaired renal tissue perfusion and GFR and increased fractional glucose excretion associated with decreased expression of SGLT2, SGLT3, and GLUT2 after LPS injection. Similar alterations were observed after application of TNF-alpha, IL-1 beta, IL- 6, or IFN-gamma. To clarify the role of proinflammatory cytokines, we performed LPS injections in knockout mice with deficiencies for TNF-alpha, IL- 1 receptor type 1, IFN-gamma, or IL- 6 as well as LPS injections in glucocorticoid-treated wild-type mice. LPS-induced alterations of glucose transporters also were present in single-cytokine knockout mice. In contrast, glucocorticoid treatment clearly attenuated LPS-induced changes in renal glucose transporter expression and improved GFR and fractional glucose excretion. LPS-induced decrease of renal perfusion was not improved by glucocorticoids, indicating a minor role of ischemia in the development of septic renal dysfunction. Our results demonstrate modifications of tubular glucose transporters during severe inflammation that are probably mediated by proinflammatory cytokines and account for the development of ARF with increased fractional glucose excretion. In addition, our findings provide an explanation why single anti-cytokine strategies fail in the therapy of septic patients and contribute to an understanding of the beneficial effects of glucocorticoids on septic renal dysfunction.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SEPTIC SHOCK; MESSENGER-RNA; ENDOTOXIC-SHOCK; RESPONSE SYNDROME; DOWN-REGULATION; DOUBLE-BLIND; RAT-KIDNEY; FAILURE; MICE; HYDROCORTISONE; sepsis; acute renal failure; tubular function; lipopolysaccharide; cytokines; glucocorticoids |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Anästhesiologie Medicine > Lehreinheit Pharmakologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 22 Dec 2020 10:54 |
| Last Modified: | 22 Dec 2020 10:54 |
| URI: | https://pred.uni-regensburg.de/id/eprint/33191 |
Actions (login required)
 |
View Item |
