Insulin-secretion, Hypoglycemic And Therapeutic Effect Of Antibacterial Peptide Dybowskin-2CDYa On Type 2 Diabetes Mellitus Rats

Antibacterial peptides(AMPs), with wide antimicrobial spectrum, low antigenicity, and thermal stability, is a small molecule polypeptide produced by the organism itself which can be used for exogenous pathogens resistance. Amphibians, with moist and exposed skin, often lives in complex ecological environment, and the skin can secrete antibacterial active materials to resist to the microbial invasion of outside world. With the deepening of the research of function of frog skin antimicrobial peptides, the promotion of insulin secretion of some peptides were found. In recent years, J. Michael Conlon et.al reported a wide variety of peptides which have the function of promoting insulin secretion from amphibian antibacterial peptides. Compared with the traditional glucose-lowering drugs, the peptides in the body are not easy to be degraded, hypoglycemic effect are worked under the condition of high sugar and can promote the islet cell proliferation, making it an efficient and safe new drugs for the treatment of â…¡ diabetes.In previous work of our laboratory, we got a series of frog skin antibacterial peptides from the northeast frog skin, one of them was named Dybowskin-2 CDYa(SAVGRHGRRFGLRKHRKH). Because of its low thermal stability, then we replaced the six base of this antibacterial peptide and named it AWRK6(SWVGKHGKKFGLKKHKKH). Early experimental results showed that Dybowskin-2 CDYa has a good promotion of insulin secretion.To identify the hypoglycemic effect of antibacterial peptide Dybowskin-2 CDYa in the body, streptozotocin(STZ) was used to construct model of type 2 diabetic rats. Results showed that through intraperitoneal injection of the concentration of 100 nmol/L antibacterial peptide Dybowskin-2 CDYa, blood sugar levels reduced in diabetes model rats since 30 min, blood sugar levels dropped to normal level(<11.1 mol/L) until 210 min. Intraperitoneal injection of same concentration of Dybowskin-2 CDYa were conducted in rats of normal group, blood sugar levels remained within the normal range, no hypoglycemia were detected, this result showed that the hypoglycemic effect of antimicrobial peptide Dybowskin-2 CDYa occurs only under the condition of high sugar, and will not lead to hypoglycemia.To identify the function of tissue protection of antibacterial peptide Dybowskin-2 CDYa in body, the rat liver, pancreas, muscle tissue were embedded by paraffin, HE staining, slices making, and immunohistochemical observation were conducted. HE staining results showed that, comparing with the antibacterial peptide Dybowskin-2 CDYa treatment group and the control group, the number of fat cells and its volume in tissue of rats were reduced in a certain extent. Immunohistochemical results showed that tissue cell apoptosis were reduced in the antibacterial peptide Dybowskin-2 CDYa treatment group. This study lay of the theoretical and experimental basis for polypeptide drugs development with function of insulin release active using antibacterial peptides Dybowskin-2 CDYa.