Detection of localized changes in the metabolism of hyperpolarized gluconeogenic precursors 13 C-lactate and 13 C-pyruvate in kidney and liver.
PURPOSE
The purpose of this study was to characterize tissue-specific alterations in metabolism of hyperpolarized (HP) gluconeogenic precursors 13 C-lactate and 13 C-pyruvate by rat liver and kidneys under conditions of fasting or insulin-deprived diabetes.


METHODS
Seven normal rats were studied by MR spectroscopic imaging of both HP 13 C-lactate and 13 C-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.


RESULTS
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 of 13 C-bicarbonate to total 13 C 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.


CONCLUSION
MRI of HP 13 C 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.
['von Morze|Cornelius|C|', 'Chang|Gene-Yuan|GY|', 'Larson|Peder E Z|PE|0000-0003-4183-3634', 'Shang|Hong|H|', 'Allu|Prasanna K R|PK|', 'Bok|Robert A|RA|', 'Crane|Jason C|JC|', 'Olson|Marram P|MP|', 'Tan|Chou T|CT|', 'Marco-Rius|Irene|I|', 'Nelson|Sarah J|SJ|', 'Kurhanewicz|John|J|', 'Pearce|David|D|', 'Vigneron|Daniel B|DB|']
D000818:Animals D066241:Carbon-13 Magnetic Resonance Spectroscopy D005943:Gluconeogenesis D005947:Glucose D007668:Kidney D019344:Lactic Acid D008099:Liver D008297:Male D008657:Metabolic Clearance Rate D019289:Pyruvic Acid D051381:Rats D017207:Rats, Sprague-Dawley D015203:Reproducibility of Results D012680:Sensitivity and Specificity
fasting diabetes streptozotocin dynamic nuclear polarization gluconeogenesis