Glucoregulatory and Anti-Inflammatory Activities of Peptide Fractions Separated by Electrodialysis with Ultrafiltration Membranes from Salmon Protein Hydrolysate and Identification of Four Novel Glucoregulatory Peptides.

Geneviève Pilon,Karina Danielle Pereira,Loïc Henaux,Laurent Bazinet,Jacinthe Thibodeau,Tom Gill,André Marette

doi:10.3390/membranes11070528

Abstract

Natural bioactive peptides are suitable candidates for preventing the development of Type 2 diabetes (T2D), by reducing the various risk factors. The aim of this study was to concentrate glucoregulatory and anti-inflammatory peptides, from salmon by-products, by electrodialysis with ultrafiltration membrane (EDUF), and to identify peptides responsible for these bioactivities. Two EDUF configurations (1 and 2) were used to concentrate anionic and cationic peptides, respectively. After EDUF separation, two fractions demonstrated interesting properties: the initial fraction of the EDUF configuration 1 and the final fraction of the EDUF configuration 2 both showed biological activities to (1) increase glucose uptake in L6 muscle cells in insulin condition at 1 ng/mL (by 12% and 21%, respectively), (2) decrease hepatic glucose production in hepatic cells at 1 ng/mL in basal (17% and 16%, respectively), and insulin (25% and 34%, respectively) conditions, and (3) decrease LPS-induced inflammation in macrophages at 1 g/mL (45% and 30%, respectively). More impressive, the initial fraction of the EDUF configuration 1 (45% reduction) showed the same effect as the phenformin at 10 μM (40%), a drug used to treat T2D. Thirteen peptides were identified, chemically synthesized, and tested in-vitro for these three bioactivities. Thus, four new bioactive peptides were identified: IPVE increased glucose uptake by muscle cells, IVDI and IEGTL decreased hepatic glucose production (HGP) of insulin, whereas VAPEEHPTL decreased HGP under both basal condition and in the presence of insulin. To the best of our knowledge, this is the first time that (1) bioactive peptide fractions generated after separation by EDUF were demonstrated to be bioactive on three different criteria; all involved in the T2D, and (2) potential sequences involved in the improvement of glucose uptake and/or in the regulation of HGP were identified from a salmon protein hydrolysate.

Highlights

Type 2 diabetes (T2D) mellitus is a complex metabolic disorder and progressive disease [1]
Glucose intolerance has been identified as a major metabolic abnormality involved in the metabolic syndrome and a diabetes precursor, resulting in a deficiency of insulin to mediate muscle glucose uptake and to inhibit hepatic glucose production [30]
All these results suggested that anionic peptides have gluco-regulatory effects by enhancing the glucose uptake in L6 muscle cells and decreasing the glucose production in hepatic cells, while cationic peptides decreased the inflammation in activated macrophages

Summary

Introduction

Type 2 diabetes (T2D) mellitus is a complex metabolic disorder and progressive disease [1]. According to the World Health Organization (WHO), non-communicable diseases (including T2D). More than 36 million people die from. NCDs (63% of global deaths) [3]. According to a recent report from the International Diabetes Federation, in 2019, 463 million of people aged between 20 to 79 years had the T2D, [4]. In order to prevent NCDs and T2D, promoting healthy diet and physical activity are an integral part of the WHO’s “Global action plan for the prevention and control of non-communicable diseases 2013–2020” [3]. A high proportion of people at risk do not follow these recommendations, and the T2D continues to progress [5]

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