Next Article in Journal
Switching Circuit Optimization for Matrix Gradient Coils
Previous Article in Journal
Regional Ultrahigh-Resolution Rescan in a Clinical Whole-Body CT Scanner Using a Contact Detector Insert
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Tomography
Volume 5
Issue 2
10.18383/j.tom.2019.00003
tomography-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
Tomography is published by MDPI from Volume 7 Issue 1 (2021). Previous articles were published by another publisher in Open Access under a CC-BY (or CC-BY-NC-ND) licence, and they are hosted by MDPI on mdpi.com as a courtesy and upon agreement with Grapho, LLC.
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

High Intrarenal Lactate Production Inhibits the Renal Pseudohypoxic Response to Acutely Induced Hypoxia in Diabetes

by
Christoffer Laustsen
1,*,
Kasper Lipsø
2,3,
Jakob Appel Østergaard
4,
Per Mose Nielsen
1,
Lotte Bonde Bertelsen
1,
Allan Flyvbjerg
5,6,
Michael Pedersen
1,
Fredrik Palm
7 and
Jan Henrik Ardenkjær-Larsen
2,3,8
1
Department of Clinical Medicine, MR Research Centre, Aarhus University, Aarhus, Denmark
2
Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
3
Department of Electrical Engineering, Technical University of Denmark, Kgs Lyngby, Denmark
4
Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark
5
Steno Diabetes Center Copenhagen, The Capital Region of Denmark, Gentofte, Denmark
6
University of Copenhagen, Copenhagen, Denmark
7
Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden
8
GE Healthcare, Copenhagen, Denmark
*
Author to whom correspondence should be addressed.
Tomography 2019, 5(2), 239-247; https://doi.org/10.18383/j.tom.2019.00003
Submission received: 5 March 2019 / Revised: 3 April 2019 / Accepted: 2 May 2019 / Published: 1 June 2019
Versions Notes

Abstract

Intrarenal hypoxia develops within a few days after the onset of insulinopenic diabetes in an experimental animal model (ie, a model of type-1 diabetes). Although diabetes-induced hypoxia results in increased renal lactate formation, mitochondrial function is well maintained, a condition commonly referred to as pseudohypoxia. However, the metabolic effects of significantly elevated lactate levels remain unclear. We therefore investigated in diabetic animals the response to acute intrarenal hypoxia in the presence of high renal lactate formation to delineate mechanistic pathways and compare these findings to healthy control animals. Hyperpolarized 13C-MRI and blood oxygenation level–dependent 1H-MRI was used to investigate the renal metabolism of [1-13C]pyruvate and oxygenation following acutely altered oxygen content in the breathing gas in a streptozotocin rat model of type-1 diabetes with and without insulin treatment and compared with healthy control rats. The lactate signal in the diabetic kidney was reduced by 12%–16% during hypoxia in diabetic rats irrespective of insulin supplementation. In contrast, healthy controls displayed the well-known Pasteur effect manifested as a 10% increased lactate signal following reduction of oxygen in the inspired air. Reduced expression of the monocarboxyl transporter-4 may account for altered response to hypoxia in diabetes with a high intrarenal pyruvate-to-lactate conversion. Reduced intrarenal lactate formation in response to hypoxia in diabetes shows the existence of a different metabolic phenotype, which is independent of insulin, as insulin supplementation was unable to affect the pyruvate-to-lactate conversion in the diabetic kidney.
Keywords: MRI; type 1-diabetes; kidney; renal metabolism; hyperpolarization MRI; type 1-diabetes; kidney; renal metabolism; hyperpolarization

Share and Cite

MDPI and ACS Style

Laustsen, C.; Lipsø, K.; Østergaard, J.A.; Nielsen, P.M.; Bertelsen, L.B.; Flyvbjerg, A.; Pedersen, M.; Palm, F.; Ardenkjær-Larsen, J.H. High Intrarenal Lactate Production Inhibits the Renal Pseudohypoxic Response to Acutely Induced Hypoxia in Diabetes. Tomography 2019, 5, 239-247. https://doi.org/10.18383/j.tom.2019.00003

AMA Style

Laustsen C, Lipsø K, Østergaard JA, Nielsen PM, Bertelsen LB, Flyvbjerg A, Pedersen M, Palm F, Ardenkjær-Larsen JH. High Intrarenal Lactate Production Inhibits the Renal Pseudohypoxic Response to Acutely Induced Hypoxia in Diabetes. Tomography. 2019; 5(2):239-247. https://doi.org/10.18383/j.tom.2019.00003

Chicago/Turabian Style

Laustsen, Christoffer, Kasper Lipsø, Jakob Appel Østergaard, Per Mose Nielsen, Lotte Bonde Bertelsen, Allan Flyvbjerg, Michael Pedersen, Fredrik Palm, and Jan Henrik Ardenkjær-Larsen. 2019. "High Intrarenal Lactate Production Inhibits the Renal Pseudohypoxic Response to Acutely Induced Hypoxia in Diabetes" Tomography 5, no. 2: 239-247. https://doi.org/10.18383/j.tom.2019.00003

APA Style

Laustsen, C., Lipsø, K., Østergaard, J. A., Nielsen, P. M., Bertelsen, L. B., Flyvbjerg, A., Pedersen, M., Palm, F., & Ardenkjær-Larsen, J. H. (2019). High Intrarenal Lactate Production Inhibits the Renal Pseudohypoxic Response to Acutely Induced Hypoxia in Diabetes. Tomography, 5(2), 239-247. https://doi.org/10.18383/j.tom.2019.00003

Article Metrics

Back to TopTop