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 Chittepu,Tzayhri Gallardo-Velázquez,Guillermo Osorio-Revilla

doi:10.3390/ijms20051228

Poonam Kalhotra, Veera Chittepu + Show 2 more

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https://doi.org/10.3390/ijms20051228

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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.

Highlights

IntroductionA global disease characterized as an impairment in insulin secretion (type 1 diabetes mellitus), insulin resistance (type 2 diabetes mellitus) leads to hyperglycemia, and are two of the most important health problems faced by every country
Diabetes mellitus, a global disease characterized as an impairment in insulin secretion, insulin resistance leads to hyperglycemia, and are two of the most important health problems faced by every country
Insulin therapy is most commonly recommended for type 1 diabetes mellitus patients [3] whereas, sulfonylureas, meglitinides, biguanides, glitazones, α-glucoside inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors and combination therapies are the most recommended therapies for type 2 diabetes mellitus patients, and all these antidiabetic therapies possess side effects like respiratory infection, hypoglycemia, hepatic and cardiovascular complications [4,5]

Summary

Introduction

A global disease characterized as an impairment in insulin secretion (type 1 diabetes mellitus), insulin resistance (type 2 diabetes mellitus) leads to hyperglycemia, and are two of the most important health problems faced by every country. Insulin therapy is most commonly recommended for type 1 diabetes mellitus patients [3] whereas, sulfonylureas (e.g., glimepiride), meglitinides (e.g., repaglinide), biguanides (e.g., metformin), glitazones (e.g., rosiglitazone), α-glucoside inhibitors (acarbose), dipeptidyl peptidase-4 (DPP-4) inhibitors (e.g., sitagliptin) and combination therapies (e.g., metformin and rosiglitazone, insulin and metformin) are the most recommended therapies for type 2 diabetes mellitus patients, and all these antidiabetic therapies possess side effects like respiratory infection, hypoglycemia, hepatic and cardiovascular complications [4,5]. Clinical trials were carried out to demonstrate the benefits of combination therapy in treating insulin resistance.

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