Hyperpolarized pyruvate to measure the influence of PKM2 activation on glucose metabolism in the healthy kidney
| Autor: | Christoffer Laustsen, Thorsten Sadowski, Sven Ruf, Esben Søvsø Szocska Hansen, Lotte Bonde Bertelsen |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
medicine.medical_specialty Pyruvate Kinase hyperpolarization kidney MRI PKM2 Renal function PKM2 Carbohydrate metabolism Kidney Diabetic nephropathy Internal medicine Pyruvic Acid medicine Animals Humans Radiology Nuclear Medicine and imaging Glycolysis Lactic Acid Rats Wistar Spectroscopy Alanine Activator (genetics) Chemistry Hydrogen-Ion Concentration medicine.disease Enzyme Activation Bicarbonates Disease Models Animal Glucose Endocrinology medicine.anatomical_structure Hematocrit Molecular Medicine Pyruvate kinase |
| Zdroj: | Bertelsen, L B, Hansen, E S S, Sadowski, T, Ruf, S & Laustsen, C 2021, ' Hyperpolarized pyruvate to measure the influence of PKM2 activation on glucose metabolism in the healthy kidney ', NMR in Biomedicine, vol. 34, no. 11, e4583 . https://doi.org/10.1002/nbm.4583 |
| DOI: | 10.1002/nbm.4583 |
| Popis: | The purpose of the current study was to investigate if hyperpolarized [1-C-13]pyruvate can inform us on the metabolic consequences for the kidney glucose metabolism upon treatment with the pyruvate kinase M2 (PKM2) activator TEPP-46, which has shown promise as a novel therapeutic target for diabetic nephropathy. A healthy male Wistar rat model was employed to study the conversion of [1-C-13]pyruvate to [1-C-13]lactate in the kidney 2 and 4 h after treatment with TEPP-46. All rats were scanned with hyperpolarized [1-C-13]pyruvate kidney MR and vital parameters and blood samples were taken after scanning. The PKM2 activator TEPP-46 increases the glycolytic activity in the kidneys, leading to an increased lactate production, as seen by hyperpolarized pyruvate-to-lactate conversion. The results are supported by an increase in blood lactate, a decreased blood glucose level and an increased pyruvate kinase (PK) activity. The metabolic changes observed in both kidneys following treatment with TEPP-46 are largely independent of renal function and could as such represent a new and extremely sensitive metabolic readout for future drugs targeting PKM2. These results warrant further studies in disease models to evaluate if [1-C-13]pyruvate-to-[1-C-13]lactate conversion can predict treatment outcome. |
| Databáze: | OpenAIRE |
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