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Sci Rep. 2018 Feb 1;8(1):2088. doi: 10.1038/s41598-018-20264-w.

Non-invasive detection of divergent metabolic signals in insulin deficiency vs. insulin resistance in vivo.

Author information

1
Department of Radiology and Biomedical Imaging, University of California, San Francisco, United States. cornelius.vonmorze@ucsf.edu.
2
Division of Nephrology, Department of Medicine, University of California, San Francisco, United States.
3
Department of Radiology and Biomedical Imaging, University of California, San Francisco, United States.

Abstract

The type 2 diabetic phenotype results from mixed effects of insulin deficiency and insulin resistance, but the relative contributions of these two distinct factors remain poorly characterized, as do the respective roles of the gluconeogenic organs. The purpose of this study was to investigate localized in vivo metabolic changes in liver and kidneys of contrasting models of diabetes mellitus (DM): streptozotocin (STZ)-treated wild-type Zucker rats (T1DM) and Zucker diabetic fatty (ZDF) rats (T2DM). Intermediary metabolism was probed using hyperpolarized (HP) [1-13C]pyruvate MRI of the liver and kidneys. These data were correlated with gene expression data for key mediators, assessed using rtPCR. Increased HP [1-13C]lactate was detected in both models, in association with elevated gluconeogenesis as reflected by increased expression of phosphoenolpyruvate carboxykinase. In contrast, HP [1-13C]alanine diverged between the two models, increasing in ZDF rats, while decreasing in the STZ-treated rats. The differences in liver alanine paralleled differences in key lipogenic mediators. Thus, HP [1-13C]alanine is a marker that can identify phenotypic differences in kidneys and liver of rats with T1DM vs. T2DM, non-invasively in vivo. This approach could provide a powerful diagnostic tool for characterizing tissue metabolic defects and responses to treatment in diabetic patients with ambiguous systemic manifestations.

PMID:
29391429
PMCID:
PMC5794967
DOI:
10.1038/s41598-018-20264-w
[Indexed for MEDLINE]
Free PMC Article

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