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Diabetes mellitus type I effects on polyploidization, DNA methylation and gene expression on mouse hepatocytes

Grant number: 13/15339-3
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): September 01, 2013
Effective date (End): August 31, 2014
Field of knowledge:Biological Sciences - Genetics
Principal Investigator:Maria Luiza Silveira Mello
Grantee:Natália de Brito Damasceno
Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated research grant:10/50015-6 - Chromatin structure and organization with aging and diabetes compared to induced changes in epigenetic markers, AP.TEM

Abstract

The hyperglycemia caused by diabetes mellitus type I (DMTI) induces changes in polyploidy and chromatin structure of mouse hepatocytes. These changes may be related to modifications in the abundance and activity of key regulatory proteins like the DNA methyltransferases (DNMT) as well as in gene expression. In a project previously supported by FAPESP (Proc. 2012/16232-5) we have determined decrease in the abundance of DNA methylation in non-obese diabetic (NOD) mice under hyperglycemic conditions. In a cell culture model of human hepatocarcinoma we have detected plasticity in gene expression but not in epigenetic marks under DMTI-mimic conditions. There are reports in the literature showing that in diabetic patients some consequences of the diabetes disorder like retinopathy are not reverted even after an intensive treatment with insulin. This phenomenon was called hyperglycemic memory. In the present study we intend to demonstrate in an in vivo mouse model the occurrence of plasticity in changes related to polyploidy, abundance of DNA methylation and expression of specific genes in mouse diabetic hepatocytes following treatment with insulin. (AU)