Antimicrobial peptide chensinin-1b attenuates T2DM progression in atherosclerotic ApoE^-/- mice

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.

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.

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.

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.