Comparative identification of GspA in the proteome and genome of probiotic and non-probiotic bacteria for the treatment of type ۲ diabetes

GLP-۱ is one of the types of incretins or digestive hormones and one of the strongest stimulants of insulin release in response to glucose. Studies have shown that GLP-۱ activity is reduced in patients with type ۲ diabetes. Administration of GLP-۱ to patients with type ۲ diabetes leads to normalization of hyperglycemic conditions. Therefore, strategies based on increasing and inducing GLP-۱ seem to be a good goal for the treatment of type ۲ diabetes. GspA is a secretory peptide with the MAADIISTIGDLVKWIIDTVNKFKK sequence that has GLP-۱ secretion stimulating activity. In this study, GspA comparisons in the proteome and genome of probiotic and non-probiotic bacteria were investigated using NCBI-Genome and UniProt-Proteome databases. The results showed that GspA sequence was present in Staphylococcus epidermidis Scl۳۱ with high similarity in several other strains of Staphylococcus, but was not observed in any of the probiotics. Studies on human L cells and intestinal enteroids have shown that GspA alone is sufficient to increase GLP-۱ secretion. The results of administration of GspA-producing Staphylococcus epidermidis in high-fat-fed mice showed a significant reduction in markers associated with obesity and type ۲ diabetes, including obesity and hyperinsulinemia. GspA stimulates GLP-۱ through calcium signaling. GspA can help establish a microbial peptide-based treatment for obesity and type ۲ diabetes by creating a host-microbial interaction. Finally, in the absence of GspA sequence in probiotics, gene construct was designed by inserting the gene sequence of this peptide with inducer and secretory signal in the probiotic bacterium Lactobacillus plantarum as a suitable treatment strategy for the treatment of type ۲ diabetes.

کلیدواژه ها:

Probiotics ، Type ۲ diabetes ، GspA ، GLP-۱