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

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 investiga...

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Autores principales:	Cornelius von Morze, Prasanna K. R. Allu, Gene Y. Chang, Irene Marco-Rius, Eugene Milshteyn, Zhen J. Wang, Michael A. Ohliger, Catherine E. Gleason, John Kurhanewicz, Daniel B. Vigneron, David Pearce
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0da58e9c958344c2a4144ef02696a579
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spelling	oai:doaj.org-article:0da58e9c958344c2a4144ef02696a5792021-12-02T15:07:56ZNon-invasive detection of divergent metabolic signals in insulin deficiency vs. insulin resistance in vivo10.1038/s41598-018-20264-w2045-2322https://doaj.org/article/0da58e9c958344c2a4144ef02696a5792018-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-20264-whttps://doaj.org/toc/2045-2322Abstract 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.Cornelius von MorzePrasanna K. R. AlluGene Y. ChangIrene Marco-RiusEugene MilshteynZhen J. WangMichael A. OhligerCatherine E. GleasonJohn KurhanewiczDaniel B. VigneronDavid PearceNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-12 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Cornelius von Morze Prasanna K. R. Allu Gene Y. Chang Irene Marco-Rius Eugene Milshteyn Zhen J. Wang Michael A. Ohliger Catherine E. Gleason John Kurhanewicz Daniel B. Vigneron David Pearce Non-invasive detection of divergent metabolic signals in insulin deficiency vs. insulin resistance in vivo
description	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.
format	article
author	Cornelius von Morze Prasanna K. R. Allu Gene Y. Chang Irene Marco-Rius Eugene Milshteyn Zhen J. Wang Michael A. Ohliger Catherine E. Gleason John Kurhanewicz Daniel B. Vigneron David Pearce
author_facet	Cornelius von Morze Prasanna K. R. Allu Gene Y. Chang Irene Marco-Rius Eugene Milshteyn Zhen J. Wang Michael A. Ohliger Catherine E. Gleason John Kurhanewicz Daniel B. Vigneron David Pearce
author_sort	Cornelius von Morze
title	Non-invasive detection of divergent metabolic signals in insulin deficiency vs. insulin resistance in vivo
title_short	Non-invasive detection of divergent metabolic signals in insulin deficiency vs. insulin resistance in vivo
title_full	Non-invasive detection of divergent metabolic signals in insulin deficiency vs. insulin resistance in vivo
title_fullStr	Non-invasive detection of divergent metabolic signals in insulin deficiency vs. insulin resistance in vivo
title_full_unstemmed	Non-invasive detection of divergent metabolic signals in insulin deficiency vs. insulin resistance in vivo
title_sort	non-invasive detection of divergent metabolic signals in insulin deficiency vs. insulin resistance in vivo
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/0da58e9c958344c2a4144ef02696a579
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Non-invasive detection of divergent metabolic signals in insulin deficiency vs. insulin resistance in vivo

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