Discovery of galangin as a potential DPP-4 inhibitor that improves insulin-stimulated skeletal muscle glucose uptake: A combinational therapy for diabetes

Poonam Kalhotra, Veera C.S.R. Chittepu, Guillermo Osorio-Revilla, Tzayhri Gallardo-Velázquez

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Abstract

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.

Original languageEnglish
Article number1228
JournalInternational Journal of Molecular Sciences
Volume20
Issue number5
DOIs
StatePublished - 1 Mar 2019

Fingerprint

Dipeptidyl-Peptidase IV Inhibitors
skeletal muscle
insulin
Insulin
Dipeptidyl Peptidase 4
Medical problems
glucose
inhibitors
Glucose
Muscle
therapy
Skeletal Muscle
diabetes mellitus
health
Diabetes Mellitus
muscle cells
Molecular Docking Simulation
Health
Therapeutics
muscles

Keywords

  • Combination therapy
  • Diabetes mellitus
  • DPP-4 inhibitor
  • Galangin
  • Molecular docking
  • Skeletal muscle cell health

Cite this

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abstract = "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.",
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AU - Osorio-Revilla, Guillermo

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