Genomic profiling of type-1 adult diabetic and aged normoglycemic mouse liver

Flávia G Ghiraldini, André B Silveira, Dirk-Jan Kleinjan, Nick Gilbert, Maria Luiza S Mello

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND: Hyperglycemia induces chromatin remodeling with consequences on differential gene expression in mouse hepatocytes, similar to what occurs during aging. The liver is the central organ for the regulation of glucose homeostasis and xenobiotic and lipid metabolism and is affected by insulin signaling. The precise transcriptional profiling of the type-1 diabetic liver and its comparison to aging have not been elucidated yet.

METHODS: Here, we studied the differential genomic expression of mouse liver cells under adult hyperglycemic and aged normoglycemic conditions using expression arrays.

RESULTS: Differential gene expression involved in an increase in glucose and impaired lipid metabolism were detected in the type-1 diabetic liver. In this regard, Ppargc1a presents an increased expression and is a key gene that might be regulating both processes. The differential gene expression observed may also be associated with hepatic steatosis in diabetic mouse liver, as a secondary disease. Similarly, middle-aged mice presented differential expression of genes involved in glucose, lipid and xenobiotic metabolism. These genes could be associated with an increase in polyploidy, but the consequences of differential expression were not as drastic as those observed in diabetic animals.

CONCLUSIONS: Taken together, these findings provide new insights into gene expression profile changes in type-1 diabetic liver. Ppargc1a was found to be the key-gene that increases glucose metabolism and impairs lipid metabolism impairment. The novel results reported here open new areas of investigation in diabetic research and facilitate the development of new strategies for gene therapy.

Original languageEnglish
Pages (from-to)19
JournalBMC Endocrine Disorders
Volume14
DOIs
Publication statusPublished - 3 Mar 2014

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