Physiological effects of Type 2 diabetes on mRNA processing and gene expression

Abstract

Characteristics of Type 2 diabetes include both high blood glucose (hyperglycemia) and raised cholesterol and triglycerides (hyperlipidemia). Several studies have now shown that both hyperglycemia and hyperlipidemia can alter gene expression by disrupting physiological mechanisms of gene regulation, including alternative mRNA splicing, epigenetic gene regulation and miRNA-mediated regulation of gene expression. These processes may also be influenced by intracellular oxidative stress, which is increased in diabetes and in response to hyperglycemia and hyperlipidemia. Many pathways relevant to diabetes are affected by altered gene expression, including lipid and glucose metabolism and oxidative phosphorylation. This article considers how hyperglycemia and hyperlipidemia can alter gene expression in diabetes, which could potentially contribute to the worsening of the diabetic phenotype and diabetic complications.

Keywords::

• alternative splicing
• diabetes
• epigenetic
• gene expression
• glucolipotoxicity
• hyperglycemia
• hyperlipidemia
• miRNA
• oxidative stress

Acknowledgement

The authors would like to thank Jonathan Locke for his critical appraisal of the manuscript.

Financial & competing interests disclosure

The authors thank the Peninsula College of Medicine and Dentistry for providing funding. Lorna W Harries is supported by Wellcome Trust grants number 081278/Z/06/Z and 099845/Z/09/Z. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.