Double role of anti-diabetic drugs
doi:10.1038/nindia.2015.45 Published online 8 April 2015Certain anti-diabetic agents could also help ameliorate the stress on the endoplasmic reticulum (ER), the protein quality control machinery of the cell. This dual action could help develop new-generation anti-diabetic agents with ER stress inhibitory potential as one of the important drug targeting mechanism, according to new research1.
Some anti-diabetic drugs have anti-inflammatory and anti-oxidant properties. Stress on the ER could hamper lipid biosynthesis, calcium storage, and protein folding and become an underlying cause for several diseases. Beta cells are the most sensitive to ER stress because of the large fluctuations in protein synthesis (including insulin) they face daily. This makes ER stress as an important component of etiology in the genesis of diabetes and its complications.
The research, led by Muthuswamy Balasubramanyam at the Madras Diabetes Research Foundation, identified the activity of secreted alkaline phosphatase (SEAP) as a surrogate marker of ER stress in β-cells. They looked at β-cells under elevated glucose and fatty acid levels (glucolipotoxicity) as seen in patients with type 2 diabetes.
The researchers found that certain existing anti-diabetic agents — Metformin, Vildagliptin and Exenatide — reduced ER stress by transcriptionally decreasing the gene expression of several ER stress markers. These could help make new-generation anti-diabetic agents with ER stress inhibitory potential, Balasubramanyam says.
1. Lenin, R. et al. SEAP activity serves for demonstrating ER stress induction by glucolipotoxicity as well as testing ER stress inhibitory potential of therapeutic agents. Mol. Cell Biochem. (2015) doi: 10.1007/s11010-015-2387-1