Novel application of complementary imaging techniques to examine in vivo glucose metabolism in the kidney

Takashi Hato, Allon Friedman, Henry Mang, Zoya Plotkin, Shataakshi Dube, Gary Hutchins, Paul Territo, Brian P. McCarthy, Amanda A. Riley, Kumar Pichumani, Craig R. Malloy, Robert Harris, Pierre Dagher, Timothy Sutton

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The metabolic status of the kidney is a determinant of injury susceptibility and a measure of progression for many disease processes; however, noninvasive modalities to assess kidney metabolism are lacking. In this study, we employed positron emission tomography (PET) and intravital multiphoton microscopy (MPM) to assess cortical and proximal tubule glucose tracer uptake, respectively, following experimental perturbations of kidney metabolism. Applying dynamic image acquisition PET with 2-18fluoro-2-deoxyglucose (18F-FDG) and tracer kinetic modeling, we found that an intracellular compartment in the cortex of the kidney could be distinguished from the blood and urine compartments in animals. Given emerging literature that the tumor suppressor protein p53 is an important regulator of cellular metabolism, we demonstrated that PET imaging was able to discern a threefold increase in cortical18F-FDG uptake following the pharmacological inhibition of p53 in animals. Intravital MPM with the fluorescent glucose analog 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxyglucose (2-NBDG) provided increased resolution and corroborated these findings at the level of the proximal tubule. Extending our observation of p53 inhibition on proximal tubule glucose tracer uptake, we demonstrated by intravital MPM that pharmacological inhibition of p53 diminishes mitochondrial potential difference. We provide additional evidence that inhibition of p53 alters key metabolic enzymes regulating glycolysis and increases intermediates of glycolysis. In summary, we provide evidence that PET is a valuable tool for examining kidney metabolism in preclinical and clinical studies, intravital MPM is a powerful adjunct to PET in preclinical studies of metabolism, and p53 inhibition alters basal kidney metabolism.

Original languageEnglish (US)
Pages (from-to)F717-F725
JournalAmerican Journal of Physiology - Renal Physiology
Volume310
Issue number8
DOIs
StatePublished - Apr 15 2016

Fingerprint

Positron-Emission Tomography
Kidney
Glucose
Glycolysis
Pharmacology
Tumor Suppressor Protein p53
Basal Metabolism
Kidney Cortex
Fluorodeoxyglucose F18
Deoxyglucose
Disease Progression
Observation
Urine
Intravital Microscopy
Wounds and Injuries
Enzymes
2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose

Keywords

  • Kidney
  • Multiphoton microscopy
  • P53
  • Positron emission tomography

ASJC Scopus subject areas

  • Physiology
  • Urology

Cite this

Novel application of complementary imaging techniques to examine in vivo glucose metabolism in the kidney. / Hato, Takashi; Friedman, Allon; Mang, Henry; Plotkin, Zoya; Dube, Shataakshi; Hutchins, Gary; Territo, Paul; McCarthy, Brian P.; Riley, Amanda A.; Pichumani, Kumar; Malloy, Craig R.; Harris, Robert; Dagher, Pierre; Sutton, Timothy.

In: American Journal of Physiology - Renal Physiology, Vol. 310, No. 8, 15.04.2016, p. F717-F725.

Research output: Contribution to journalArticle

Hato, Takashi ; Friedman, Allon ; Mang, Henry ; Plotkin, Zoya ; Dube, Shataakshi ; Hutchins, Gary ; Territo, Paul ; McCarthy, Brian P. ; Riley, Amanda A. ; Pichumani, Kumar ; Malloy, Craig R. ; Harris, Robert ; Dagher, Pierre ; Sutton, Timothy. / Novel application of complementary imaging techniques to examine in vivo glucose metabolism in the kidney. In: American Journal of Physiology - Renal Physiology. 2016 ; Vol. 310, No. 8. pp. F717-F725.
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AU - Hutchins, Gary

AU - Territo, Paul

AU - McCarthy, Brian P.

AU - Riley, Amanda A.

AU - Pichumani, Kumar

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AU - Dagher, Pierre

AU - Sutton, Timothy

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AB - The metabolic status of the kidney is a determinant of injury susceptibility and a measure of progression for many disease processes; however, noninvasive modalities to assess kidney metabolism are lacking. In this study, we employed positron emission tomography (PET) and intravital multiphoton microscopy (MPM) to assess cortical and proximal tubule glucose tracer uptake, respectively, following experimental perturbations of kidney metabolism. Applying dynamic image acquisition PET with 2-18fluoro-2-deoxyglucose (18F-FDG) and tracer kinetic modeling, we found that an intracellular compartment in the cortex of the kidney could be distinguished from the blood and urine compartments in animals. Given emerging literature that the tumor suppressor protein p53 is an important regulator of cellular metabolism, we demonstrated that PET imaging was able to discern a threefold increase in cortical18F-FDG uptake following the pharmacological inhibition of p53 in animals. Intravital MPM with the fluorescent glucose analog 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxyglucose (2-NBDG) provided increased resolution and corroborated these findings at the level of the proximal tubule. Extending our observation of p53 inhibition on proximal tubule glucose tracer uptake, we demonstrated by intravital MPM that pharmacological inhibition of p53 diminishes mitochondrial potential difference. We provide additional evidence that inhibition of p53 alters key metabolic enzymes regulating glycolysis and increases intermediates of glycolysis. In summary, we provide evidence that PET is a valuable tool for examining kidney metabolism in preclinical and clinical studies, intravital MPM is a powerful adjunct to PET in preclinical studies of metabolism, and p53 inhibition alters basal kidney metabolism.

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