Pancreatic Gene Variants Potentially Associated with Dipeptidyl Peptidase-4 Inhibitor Treatment Response in Type 2 Diabetes

Abstract

In the adult pancreas, the expression of the genes PAX4, KCNQ1, TCF7L2, KCNJ11, ABCC8, MTNR1B and WFS1 are mainly restricted to β cells to maintain glucose homeostasis. We have identified these genes as the main regulators of incretin-mediated actions, and therefore they may potentially influence the response of DPP-4 inhibitors. This review represents the first detailed exploration of pancreatic β-cell genes and their variant mechanisms, which could potentially affect the response of DPP-4 inhibitors in Type 2 diabetes. We have focused on the signaling pathways of these genes to understand their roles in gastrointestinal incretin-mediated effects; and finally, we sought to associate gene mechanisms with their Type 2 diabetes risk variants to predict the responses of DPP-4 inhibitors for this disease.

KEYWORDS::

• ABCC8
• dipeptidyl peptidase-4 inhibitors
• KCNJ11
• KCNQ1
• MTNR1B
• PAX4
• TCF7L2
• WFS1

Financial & competing interests disclosure

The study was supported by grants from the Ministry of Science, Technology and Innovation, Malaysia (Sciencefund: 12-02-03-2097), University of Malaya, Malaysia (University of Malaya Research Grant: RG428/12HTM) and a Postgraduate Research Grant: PG011-2012B. 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.

Additional information

Funding

The study was supported by grants from the Ministry of Science, Technology and Innovation, Malaysia (Sciencefund: 12-02-03-2097), University of Malaya, Malaysia (University of Malaya Research Grant: RG428/12HTM) and a Postgraduate Research Grant: PG011-2012B. 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.