TY - JOUR
T1 - Discovery of galangin as a potential DPP-4 inhibitor that improves insulin-stimulated skeletal muscle glucose uptake
T2 - A combinational therapy for diabetes
AU - Kalhotra, Poonam
AU - Chittepu, Veera C.S.R.
AU - Osorio-Revilla, Guillermo
AU - Gallardo-Velázquez, Tzayhri
N1 - Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2019/3/1
Y1 - 2019/3/1
N2 - Dipeptidyl peptidase-4 (DPP-4) is a well-known therapeutic drug target proven to reduce blood glucose levels in diabetes mellitus, and clinically, DPP-4 inhibitors are used in combination with other anti-diabetic agents. However, side effects and skeletal muscle health are not considered in the treatment for diabetic patients. Recently, natural compounds have been proven to inhibit DPP-4 with fewer side effects. In this work, initially, molecular docking simulations revealed that a natural compound, Galangin, possess a binding energy of −24 KJ/mol and interaction residues SER 630 and TYR 547, that are responsible for potent DPP-4 inhibition. In vitro studies showed that galangin not only inhibits DPP-4 in a concentration-dependent manner but also regulates glucose levels, enabling the proliferation of rat L6 skeletal muscle cells. The combination of galangin with insulin benefits regulation of glucose levels significantly in comparison to galangin alone (p < 0.05). These findings suggest the beneficial effect of the use of galangin, both alone or in combination with insulin, to reduce glucose levels and improve skeletal muscle health in diabetes mellitus.
AB - Dipeptidyl peptidase-4 (DPP-4) is a well-known therapeutic drug target proven to reduce blood glucose levels in diabetes mellitus, and clinically, DPP-4 inhibitors are used in combination with other anti-diabetic agents. However, side effects and skeletal muscle health are not considered in the treatment for diabetic patients. Recently, natural compounds have been proven to inhibit DPP-4 with fewer side effects. In this work, initially, molecular docking simulations revealed that a natural compound, Galangin, possess a binding energy of −24 KJ/mol and interaction residues SER 630 and TYR 547, that are responsible for potent DPP-4 inhibition. In vitro studies showed that galangin not only inhibits DPP-4 in a concentration-dependent manner but also regulates glucose levels, enabling the proliferation of rat L6 skeletal muscle cells. The combination of galangin with insulin benefits regulation of glucose levels significantly in comparison to galangin alone (p < 0.05). These findings suggest the beneficial effect of the use of galangin, both alone or in combination with insulin, to reduce glucose levels and improve skeletal muscle health in diabetes mellitus.
KW - Combination therapy
KW - DPP-4 inhibitor
KW - Diabetes mellitus
KW - Galangin
KW - Molecular docking
KW - Skeletal muscle cell health
UR - http://www.scopus.com/inward/record.url?scp=85062838956&partnerID=8YFLogxK
U2 - 10.3390/ijms20051228
DO - 10.3390/ijms20051228
M3 - Artículo
C2 - 30862104
AN - SCOPUS:85062838956
SN - 1661-6596
VL - 20
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 5
M1 - 1228
ER -