Lysophosphatidylcholine Containing Anisic Acid Is Able to Stimulate Insulin Secretion Targeting G Protein Coupled Receptors.

Anna Drzazga,Łukasz Biegała,Edyta Gendaszewska-Darmach,Marta Okulus,Anna Gliszczyńska,Magdalena Rychlicka

doi:10.3390/nu12041173

Anna Drzazga, Łukasz Biegała + Show 4 more

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https://doi.org/10.3390/nu12041173

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Abstract

Diabetes mellitus is a worldwide health problem with high rates of mortality and morbidity. Management of diabetes mellitus by dietary components is achievable especially at the initial stage of the disease. Several studies confirmed the antidiabetic activities of simple phenolic acids and lysophosphatidylcholine (LPC). The main goal of this study was to identify new potential insulin secretion modulators obtained by combining the structures of two natural compounds, namely O-methyl derivatives of phenolic acids and phospholipids. LPC and phosphatidylcholine bearing methoxylated aromatic carboxylic acids were tested as potential agents able to improve glucose-stimulated insulin secretion (GSIS) and intracellular calcium mobilization in MIN6 β pancreatic cell line. Our results show that LPC with covalently bonded molecule of p-anisic acid at the sn-1 position was able to induce GSIS and intracellular calcium flux. Notably, 1-anisoyl-2-hydroxy-sn-glycero-3-phosphocholine did not affect the viability of MIN6 cells, suggesting its potential safe use. Furthermore, we have shown that three G protein coupled receptors, namely GPR40, GPR55, and GPR119, are targeted by this LPC derivative.

Highlights

An increasing number of people suffering from diabetes is reflected in the growing market share of medications and nutraceuticals targeting this metabolic disorder
Our results indicate that GPR40 can be activated by complex lipids like LPCs [24]
We have shown that phosphorothioate analogues of LPCs did not lead to significant cyclic AMP (cAMP) increase but stimulated intracellular Ca2+ via GPR119-dependent manner [24]

Summary

Introduction

An increasing number of people suffering from diabetes is reflected in the growing market share of medications and nutraceuticals targeting this metabolic disorder. The approved pharmacologic treatment includes biguanides (metformin), which act on the liver to reduce gluconeogenesis and to cause a decrease in insulin resistance via increasing adenosine monophosphate-activated protein kinase (AMPK) signaling. Nutrients 2020, 12, 1173; doi:10.3390/nu12041173 www.mdpi.com/journal/nutrients (DPP-4) inhibitors stimulating insulin secretion and suppressing postprandial glucagon secretion in a glucose-dependent manner, and activators of the peroxisome proliferator-activated receptor-γ (PPARγ), namely thiazolidinediones which control normal skeletal muscle and hepatic insulin sensitivity and preserve pancreatic β-cell function. Other oral glucose-lowering medications such as sulfonylureas and meglitinide analogues acting directly on the islet β cells to close ATP-sensitive potassium channels and stimulate insulin secretion, acarbose, and miglitol, being α-glucosidase inhibitors which interfere with gut glucose production or amylin analogues suppressing glucagon release, are not commonly used

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