Detection of localized changes in the metabolism of hyperpolarized gluconeogenic precursors13C-lactate and13C-pyruvate in kidney and liver.
The purpose of this study was to characterize tissue-specific alterations in metabolism of hyperpolarized (HP) gluconeogenic precursors13C-lactate and13C-pyruvate by rat liver and kidneys under conditions of fasting or insulin-deprived diabetes.



Seven normal rats were studied by MR spectroscopic imaging of both HP13C-lactate and13C-pyruvate in both normal fed and 24 h fasting states, and seven additional rats were scanned after induction of diabetes by streptozotocin (STZ) with insulin withdrawal. Phosphoenolpyruvate carboxykinase (PEPCK) expression levels were also measured in liver and kidney tissues of the STZ-treated rats.



Multiple sets of significant signal modulations were detected, with graded intensity in general between fasting and diabetic states. An approximate two-fold reduction in the ratio of13C-bicarbonate to total13C signal was observed in both organs in fasting. The ratio of HP lactate-to-alanine was markedly altered, ranging from a liver-specific 54% increase in fasting, to increases of 69% and 92% in liver and kidney, respectively, in diabetes. Diabetes resulted in a 40% increase in renal lactate signal. STZ resulted in 5.86-fold and 2.73-fold increases in PEPCK expression in liver and kidney, respectively.



MRI of HP13C gluconeogenic precursors may advance diabetes research by clarifying organ-specific roles in abnormal diabetic metabolism. Magn Reson Med 77:1429-1437, 2017. © 2016 International Society for Magnetic Resonance in Medicine.
Department of Radiology and Biomedical Imaging, University of California, San Francisco, California, USA.
Cornelius
C
von Morze
Division of Nephrology, Department of Medicine, University of California, San Francisco, California, USA.
Gene-Yuan
GY
Chang
Department of Radiology and Biomedical Imaging, University of California, San Francisco, California, USA.
Peder E Z
0000-0003-4183-3634
PE
Larson
Department of Radiology and Biomedical Imaging, University of California, San Francisco, California, USA.
Hong
H
Shang
Division of Nephrology, Department of Medicine, University of California, San Francisco, California, USA.
Prasanna K R
PK
Allu
Department of Radiology and Biomedical Imaging, University of California, San Francisco, California, USA.
Robert A
RA
Bok
Department of Radiology and Biomedical Imaging, University of California, San Francisco, California, USA.
Jason C
JC
Crane
Department of Radiology and Biomedical Imaging, University of California, San Francisco, California, USA.
Marram P
MP
Olson
ISOTEC Stable Isotopes Division, Sigma-Aldrich, Miamisburg, Ohio.
Chou T
CT
Tan
Department of Radiology and Biomedical Imaging, University of California, San Francisco, California, USA.
Irene
I
Marco-Rius
Department of Radiology and Biomedical Imaging, University of California, San Francisco, California, USA.
Sarah J
SJ
Nelson
Department of Radiology and Biomedical Imaging, University of California, San Francisco, California, USA.
John
J
Kurhanewicz
Division of Nephrology, Department of Medicine, University of California, San Francisco, California, USA.
David
D
Pearce
Department of Radiology and Biomedical Imaging, University of California, San Francisco, California, USA.
Daniel B
DB
Vigneron
D000818:Animals; D066241:Carbon-13 Magnetic Resonance Spectroscopy / Q000379:methods*; D005943:Gluconeogenesis / Q000502:physiology*; D005947:Glucose / Q000096:biosynthesis*; D007668:Kidney / Q000378:metabolism*; D019344:Lactic Acid / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D019289:Pyruvic Acid / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D019344:Lactic Acid; D019289:Pyruvic Acid; D005947:Glucose
diabetes; dynamic nuclear polarization; fasting; gluconeogenesis; streptozotocin