Hyperglycemia effect of Pinctada martensii hydrolysate in diabetic db/db mice

Abstract

Ethnopharmacological relevance: Pinctada martensii (Dunker) and other marine shellfish flesh have been traditionally used in China as folk remedies regulate blood sugar.

Aim of the study: To investigate the main active constituents and the pharmacological mechanism of Pinctada martensii flesh enzymatic hydrolysate (PMH) against T2DM.

Materials and methods: The hypoglycemic activity of enzymolysis peptides from Pinctada martensii was evaluated by using db/db mice, through the influence of glycemic index, blood lipid and key protein expression of PI3K-Akt pathway. In addition, label-free quantitative proteomics was used to screen the key proteins for Pinctada martensii hydrolysate (PMH) to improve T2DM, and Western blot and qRT-PCR were used to verify the expression difference of differential proteins at protein and mRNA levels between different groups.

Results: PMH were prepared and characterized. In vivo investigations revealed that the PMH could regulate blood glucose and improve glucose tolerance and insulin tolerance, reduced serum total cholesterol, triglyceride, low-density lipoprotein cholesterol levels and increase high-density lipoprotein cholesterol levels in db/db mice. Western blot results showed that PMH could up-regulate IRS-1, P-PI3K/PI3K and P-Akt/Akt levels in db/db mice. Label-free quantitative proteomic approach was used to analyze the proteome in db/db mouse liver, 231 proteins were reversed significantly (p < 0.05), and these proteins were involved in oxidative phosphorylation, glycolysis/gluconeogenesis and other pathways. Further screened 15 proteins with FC > 1.2 could be enriched in the retinol metabolic pathway, and the proteins in this pathway were also verified.

Conclusions: PMH has hypoglycemic effect and can be used as a potential natural T2DM intervener. The hypoglycemic activity of PMH is related to its regulation of the PI3K/AKT pathway. The PI3K/AKT pathway and the retinol pathway are considered as another potential pathway for PMH to exert hypoglycemic effects.

Keywords: Hypoglycemic activity; Label-free quantitative proteomic; PI3K/Akt signaling pathways; Pinctada martensii flesh enzymatic hydrolysate; Retinol metabolic pathway.