Abstract 13544: A Naturally-Derived Spirulina Peptide Reduces the Deleterious Vascular Effects of Hyperglycemia Regulating the DPP-IV Activity and LPCAT1

Abstract

Introduction: Recently, we showed that administration of SP6 was able to exert an antihypertensive effect by enhancing endothelial vasodilation by promoting increased serum nitrite levels. New computational data revealed that SP6 is able to interact with the dipeptidylpepdase IV (DPP-IV) enzyme prompting us to hypothesize its possible involvement in the control of diabetes mellitus. Hypothesis: This work aimed to investigate the anti-diabetic role of the peptide SP6 isolated from gastro-intestinal-simulated in vitro digestion of spirulina platensis matrix. Methods: We used an experimental mouse model of type 2 diabetes. A 4-week treatment by gavage administration of SP6 was performed. By molecular biology studies and the use of mass spectrometry imaging (MALDI-MSI), the expression of GLUTs levels, DPP-IV activity and GLP-1 levels, and oxidative stress were evaluated. Results: We were able to show that daily oral administration with SP6 peptide was able to protect against hyperglycemia-induced endothelial dysfunction. Moreover, SP6 in vivo treatment was able to regulate the expression levels of GLUT1, GUT2, GLUT4 and SGLT2. In parallel, SP6 treatment was able to inhibit DPP-IV activity by promoting an increase in circulating levels of glucagon-like-peptide 1 (GLP1). Measurement of glycated hemoglobin levels after a 5-week treatment period showed that peptide treatment was able to normalize HbA1c levels, bringing its levels back below 6% and to modulate lysophosphatidylcholine and Phosphatidylcholine levels. Conclusions: In conclusion, our data support the beneficial role of SP6 on the pathophysiology of diabetes and lay the foundation to develop a novel anti-diabetic strategy.