Pancreatic gene variants potentially associated with dipeptidyl peptidase-4 inhibitor treatment response in Type 2 diabetes.
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.
Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia.
Jazlina Liza
JL
Jamaluddin
Hasniza Zaman
HZ
Huri
Shireene Ratna
SR
Vethakkan
Norlaila
N
Mustafa
D000328:Adult; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D018819:Dipeptidyl Peptidase 4 / Q000235:genetics*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage*; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D054873:Dipeptidyl-Peptidase IV Inhibitors; D004791:Enzyme Inhibitors; D018819:Dipeptidyl Peptidase 4