Insulin, a main anabolic peptide hormone, regulates metabolism of carbohydrates, proteins, lipids and affects DNA synthesis or apoptosis. Lack of insulin secretion by destroyed beta cells, in type 1 diabetic patients, not only leads to disorders in regulation of blood glucose levels, but also have direct impact on proper functioning of many key biological processes, like immune response or suppression of carcinogenic processes. Analysis of gene expression profiles allows to search for new pathogenic biomarkers and helps to understand the mode of action of pathological factors involved in the development of diabetes.

Method: For the preliminary study, we analyzed changes of transcript levels between three study groups: three healthy, three diabetic and two individuals after pancreas transplant. RNA was extracted from peripheral blood of each individual and reverse transcribed to cDNA. Changes in gene expression were quantified by Real-Time Polymerase Chain Reaction. Significantly changed genes were analyzed by ANOVA study.

Results: We observed a decrease in expression of genes NKX6-1, CDH1, PFKFB2, TP53, and GCG in diabetic patients. This was accompanied by increase in expression of HHEX, DPP4 and ABCC8. Interestingly, while the expression of TP53 is lower in patients with T1D, after pancreas transplant the level of the transcript is comparable to level in healthy individuals. In this study we also identified a group of transcripts that while upregulated in diabetic patients were downregulated after pancreas transplant (compared to healthy individuals): ABCC8 and PFKFB2.

Conclusion: Reduced expression of CDH1 (coding cadherin, involved in cell-cell interaction) in patients with type 1 diabetes could be responsible for escalating of perturbation of islet cells integrity or interactions. Furthermore, the decrease of expression of NKX6-1 (involved in transcriptional regulation of insulin) in diabetes may be connected with diminished number of pancreatic beta cells. We have also observed increased expression of DPP4, responsible for immunological responses and apoptosis, a two main processes influence on pathogenesis of T1D. After pancreas transplant expression of DPP4 is decreased, compared to diabetic individuals. In addition, in patients with T1D, we observed lower expression of gene TP53, a well-known suppressor of carcinogenesis, which could elucidate their increased risk of developing cancer.

CITATION INFORMATION: Klak M., Cichoń J., Ambrożkiewicz F., Berman A., Serwańska-Świętek M., Wszoła M. Changes in Gene Expression of Selected Genes in Patient with Type 1 Diabetes in Peripheral Blood Am J Transplant. 2017;17 (suppl 3).

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