Longitudinal analysis of hepatic transcriptome and serum metabolome demonstrates altered lipid metabolism following the onset of hyperglycemia in spontaneously diabetic biobreeding rats

Type 1 diabetes is associated with abberations of fat metabolism before and after the clinical onset of disease. It has been hypothesized that the absence of the effect of insulin in the liver contributes to reduced hepatic fat synthesis. We measured hepatic gene expression and serum metabolites bef...

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Veröffentlicht in:PloS one 2017-02, Vol.12 (2), p.e0171372-e0171372
Hauptverfasser: Regnell, Simon E, Hessner, Martin J, Jia, Shuang, Åkesson, Lina, Stenlund, Hans, Moritz, Thomas, La Torre, Daria, Lernmark, Åke
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container_title PloS one
container_volume 12
creator Regnell, Simon E
Hessner, Martin J
Jia, Shuang
Åkesson, Lina
Stenlund, Hans
Moritz, Thomas
La Torre, Daria
Lernmark, Åke
description Type 1 diabetes is associated with abberations of fat metabolism before and after the clinical onset of disease. It has been hypothesized that the absence of the effect of insulin in the liver contributes to reduced hepatic fat synthesis. We measured hepatic gene expression and serum metabolites before and after the onset of hyperglycemia in a BioBreeding rat model of type 1 diabetes. Functional pathway annotation identified that lipid metabolism was differentially expressed in hyperglycemic rats and that these pathways significantly overlapped with genes regulated by insulin. 17 serum metabolites significantly changed in concentration. All but 2 of the identified metabolites had previously been reported in type 1 diabetes, and carbohydrates were overall the most upregulated class of metabolites. We conclude that lack of insulin in the liver contributes to the changes in fat metabolism observed in type 1 diabetes. Further studies are needed to understand the clinical consequences of a lack of insulin in the liver in patients with type 1 diabetes.
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It has been hypothesized that the absence of the effect of insulin in the liver contributes to reduced hepatic fat synthesis. We measured hepatic gene expression and serum metabolites before and after the onset of hyperglycemia in a BioBreeding rat model of type 1 diabetes. Functional pathway annotation identified that lipid metabolism was differentially expressed in hyperglycemic rats and that these pathways significantly overlapped with genes regulated by insulin. 17 serum metabolites significantly changed in concentration. All but 2 of the identified metabolites had previously been reported in type 1 diabetes, and carbohydrates were overall the most upregulated class of metabolites. We conclude that lack of insulin in the liver contributes to the changes in fat metabolism observed in type 1 diabetes. Further studies are needed to understand the clinical consequences of a lack of insulin in the liver in patients with type 1 diabetes.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>28192442</pmid><doi>10.1371/journal.pone.0171372</doi><tpages>e0171372</tpages><orcidid>https://orcid.org/0000-0002-6672-8972</orcidid><oa>free_for_read</oa></addata></record>
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ispartof PloS one, 2017-02, Vol.12 (2), p.e0171372-e0171372
issn 1932-6203
1932-6203
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subjects Analysis
Animals
Annotations
Biology and Life Sciences
Blood Glucose - metabolism
Breeding
Carbohydrates
Care and treatment
Celiac disease
Cell and Molecular Biology
Cell- och molekylärbiologi
Children & youth
Clinical Medicine
Diabetes
Diabetes mellitus
Diabetes mellitus (insulin dependent)
Diabetes Mellitus, Type 1 - blood
Diabetes Mellitus, Type 1 - genetics
Diabetes Mellitus, Type 1 - metabolism
Endocrinology and Diabetes
Endokrinologi och diabetes
Fat metabolism
Fatty acids
Female
Gas Chromatography-Mass Spectrometry
Gene expression
Gene Expression Profiling - methods
Hospitals
Hyperglycemia
Hyperglycemia - blood
Hyperglycemia - genetics
Hyperglycemia - metabolism
Hypotheses
Insulin
Insulin - metabolism
Klinisk medicin
Laboratory animals
Lipid metabolism
Lipid Metabolism - genetics
Lipids
Liver
Liver - metabolism
Male
Medical and Health Sciences
Medicin och hälsovetenskap
Medicine and Health Sciences
Metabolism
Metabolites
Metabolome
Metabolomics - methods
NMR
Nuclear magnetic resonance
Pancreatic beta cells
Physical Sciences
Physiological aspects
Rats
Rats, Inbred BB
Rats, Inbred F344
Rodents
Signal Transduction - genetics
Time Factors
Transcriptome - genetics
Urine
title Longitudinal analysis of hepatic transcriptome and serum metabolome demonstrates altered lipid metabolism following the onset of hyperglycemia in spontaneously diabetic biobreeding rats
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