Abstract
BackgroundHyperglycemia 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.MethodsHere, we studied the differential genomic expression of mouse liver cells under adult hyperglycemic and aged normoglycemic conditions using expression arrays.ResultsDifferential 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.ConclusionsTaken 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.
Highlights
Hyperglycemia induces chromatin remodeling with consequences on differential gene expression in mouse hepatocytes, similar to what occurs during aging
It has been observed that the alterations in chromatin organization that occur in hepatocytes from hyperglycemic nonobese diabetic (NOD) mice might be orchestrated by the NAD+-dependent histone deacetylases Sirtuin 1 (Sirt1) and Sirtuin 6 (Sirt6) [6]
Given the similarities between diabetes and aging in mouse hepatocytes, such as increased polyploidy and chromatin remodeling, we investigated the effect of hyperglycemia and aging on genomic expression patterns in mouse liver
Summary
Hyperglycemia induces chromatin remodeling with consequences on differential gene expression in mouse hepatocytes, similar to what occurs during aging. Type-1 diabetes mellitus (T1DM) is an autoimmune disease caused by lymphocyte infiltration in the endocrine pancreas leading to destruction of β-cells and to hyperglycemia. Cardiovascular ailments, such as heart attack and atherosclerosis [1], increased prevalence of pancreas, colon and liver cancer [2]; retinopathies, nephropathies and skin conditions are examples of secondary complications caused by hyperglycemia that are accelerated when untreated. It has been observed that the alterations in chromatin organization that occur in hepatocytes from hyperglycemic NOD mice might be orchestrated by the NAD+-dependent histone deacetylases Sirt and Sirt6 [6] These sirtuins were more abundant in the NOD hyperglycemic mice, their activity was unchanged because of limiting levels of NAD+, which could promote differences in gene expression patterns [6]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
