title: Longitudinal analysis of hepatic transcriptome and serum metabolome demonstrates altered lipid metabolism following the onset of hyperglycemia in spontaneously diabetic biobreeding rats.
abstract: 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.
authors.affiliation: Diabetes and Celiac Disease Unit, Department of Clinical Sciences, Lund University/Clinical Research Centre and Skåne University Hospital, Malmö, Sweden.
authors.forename: Simon E
authors.identifier: http://orcid.org/0000-0002-6672-8972
authors.initials: SE
authors.lastname: Regnell
authors.affiliation: Max McGee National Research Center for Juvenile Diabetes, Children's Research Institute of Children's Hospital of Wisconsin, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Hessner
authors.affiliation: Max McGee National Research Center for Juvenile Diabetes, Children's Research Institute of Children's Hospital of Wisconsin, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America.
authors.forename: Shuang
authors.initials: S
authors.lastname: Jia
authors.affiliation: Diabetes and Celiac Disease Unit, Department of Clinical Sciences, Lund University/Clinical Research Centre and Skåne University Hospital, Malmö, Sweden.
authors.forename: Lina
authors.initials: L
authors.lastname: Åkesson
authors.affiliation: Swedish Metabolomics Centre, Swedish University of Agricultural Sciences, Umeå, Sweden.
authors.forename: Hans
authors.initials: H
authors.lastname: Stenlund
authors.affiliation: Swedish Metabolomics Centre, Swedish University of Agricultural Sciences, Umeå, Sweden.
authors.forename: Thomas
authors.initials: T
authors.lastname: Moritz
authors.affiliation: Diabetes and Celiac Disease Unit, Department of Clinical Sciences, Lund University/Clinical Research Centre and Skåne University Hospital, Malmö, Sweden.
authors.forename: Daria
authors.initials: D
authors.lastname: La Torre
authors.affiliation: Diabetes and Celiac Disease Unit, Department of Clinical Sciences, Lund University/Clinical Research Centre and Skåne University Hospital, Malmö, Sweden.
authors.forename: Åke
authors.initials: Å
authors.lastname: Lernmark
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001947:Breeding; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D020869:Gene Expression Profiling / Q000379:methods; D006943:Hyperglycemia / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D050356:Lipid Metabolism / Q000235:genetics*; D008099:Liver / Q000378:metabolism; D008297:Male; D055442:Metabolome; D055432:Metabolomics / Q000379:methods; D011913:Rats, Inbred BB; D011916:Rats, Inbred F344; D015398:Signal Transduction / Q000235:genetics; D013997:Time Factors; D059467:Transcriptome / Q000235:genetics*
chemical_list: D001786:Blood Glucose; D007328:Insulin