Diabetics` Cells Have Altered In Vitro Response to High Glucose

By David Douglas

NEW YORK - In studies of skin cells from identical twins discordant for type 1 diabetes (T1D), the cells from the diabetic twins had altered gene expression in response to high glucose, according to researchers.

These results, Dr. M. Luiza Caramori told Reuters Health by email, show a "metabolic memory" for the diabetic state that "has never before been documented in vitro."

Writing April 22 online in the Journal of Clinical Endocrinology & Metabolism, Dr. Caramori of the University of Minnesota, Minneapolis and colleagues say most epigenetic studies in diabetes have compared normal cells in high glucose (HG) vs normal glucose (NG) and cells returned from HG to NG.

In this study, the researchers studied skin fibroblasts from nine pairs of twins, ages 13 to 52. The cells were grown in both NG (5.5 mmol/L) and HG (25 mmol/L) for multiple passages.

"Given our interest in epigenetic effects of in vivo high glucose, (the diabetic) twins were selected from a larger cohort to have glycated hemoglobin (at least) 7.2% at the time of study and T1D for four years," the authors said.

In the T1D twins, 3308 genes were differentially expressed between NG and HG - vs only 889 genes in the nondiabetic twins.

Seven pathways had a significantly greater proportion of genes that were increased in expression between NG and HG in T1D twins: DNA replication, proteasome, cell cycle, base excision repair, homologous recombination, pyrimidine metabolism, and spliceosome pathways.

In addition, the oxidative phosphorylation pathway had a strong trend toward having more genes upregulated by HG.

"Clearly," the investigators wrote, "the response of (skin fibroblasts) to HG is greatly exaggerated and different in kind in the T1D twin."

These and other findings, the researchers continued, indicate that the influence of hyperglycemia on cellular processes in diabetes should be studied using "cells derived from individuals or animals with diabetes, and that the discordant monozygotic twins represent an excellent model for such studies."

In summary, they add, the data suggest that prior in vivo exposure to hyperglycemia markedly epigenetically alters gene expression responses to in vitro exposure to HG.

The results "open a whole new field of investigation into strategies aimed at manipulations of these healing pathways, with the ultimate goal of preventing, delaying, or even reversing the chronic complications of diabetes," Dr. Caramori said.

The Juvenile Diabetes Research Foundation supported this study.

SOURCE: https://bit.ly/1zxlBEU

J Clin Endocrinol Metab 2015.

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