Antimicrobial peptide chensinin‐1b attenuates T2DM progression in atherosclerotic ApoE −/− mice

Abstract Aims Epidemiological evidence suggests that atherosclerosis (AS) may precede or coexist with type 2 diabetes mellitus (T2DM); however, whether anti‐atherosclerotic interventions can reduce T2DM risk remains unclear. Chensinin‐1b (C‐1b), an antimicrobial peptide derived from the skin secretions of Rana chensinensis , has previously demonstrated anti‐atherosclerotic activity, suggesting a potential therapeutic effect against T2DM in the context of AS. Methods In an apolipoprotein E‐knockout ( ApoE −/− ) mice model induced by high−fat diet (HFD), the developed process of pathological changes and inflammatory levels of pancreas and aorta were detected at early, middle and late stage of AS, meanwhile the anti−atherosclerotic and anti−diabetic effects of chensinin−1b were investigated. Results In the early and middle stages of AS (6−10 weeks), mice fasting blood glucose (FBG) did not change, but atherosclerotic symptoms were significantly exhibited, such as the increased pro−inflammatory factors levels, aortic plaque and blood lipid levels. During the late stage of AS (14 weeks), it was found that the FBG of ApoE −/− mice increased significantly, the pancreas was damaged, the insulin and blood lipid levels were unbalanced, and T2DM symptoms appeared. Treatment with chensinin−1b alleviated the progression of both AS and T2DM, particularly when it was administered in the early stage of the disease. Conclusions In ApoE −/− mice, prolonged atherosclerotic pathology is associated with T2DM development. The antimicrobial peptide chensinin−1b attenuates AS and improves metabolic parameters, indicating potential multitarget intervention capabilities. These findings identify chensinin−1b as a candidate molecule for preventing AS−related metabolic abnormalities.