Food-Derived Elastin Peptides Improve Glucose Metabolism and Protect Renal Vasculature Despite Weak Dipeptidyl Peptidase-IV Inhibition

Background/Objectives: Elastin-derived peptides (EPs) from food sources may be multifunctional dietary components that support metabolic and vascular health. However, their in vivo physiological actions remain incompletely understood. This study investigated the effects of bonito bulbus arteriosus-derived EPs on glucose metabolism, GLP‑1 elevation and enhanced early-phase insulin secretion, and renal vascular integrity in stroke-prone spontaneously hypertensive rats (SHRSP) with glucose intolerance. Methods: Male SHRSP were administered EPs orally as a single dose (1,000 mg/kg) or 4-week regimen (600 mg/kg/day). Glucose tolerance, plasma GLP‑1 and insulin levels, and blood glucose levels were measured following glucose loading. Renal morphology was assessed histologically. Dpp4, Icam‑1, and Agtr1 expression was quantified in glomerular and leukocyte fractions. Leukocyte oxidative signaling was evaluated by quantifying reactive oxygen species production associated with inducible nitric oxide synthase (iNOS). Age‑matched Wistar-Kyoto rats were included as normotensive controls. Results: A single dose increased plasma GLP‑1 and insulin levels and improved glucose tolerance compared with controls. The 4‑week regimen resulted in sustained improvements in glucose tolerance, without changes in blood pressure, a lower nephrosclerosis incidence, and reduced renal and leukocytic inflammatory marker expression. Dpp4, Icam‑1, and Agtr1 expression was downregulated and leukocyte iNOS‑driven oxidative signaling was reduced. These effects occurred despite the modest DPP‑IV inhibitory activity of EPs. Conclusions: Food-derived EPs exert multi-target physiological actions, including GLP‑1 elevation with enhanced early-phase insulin secretion and leukocyte oxidative and inflammatory response suppression, that improve metabolic and renal vascular outcomes. EPs warrant further investigation as candidate functional food ingredients for metabolic and vascular health.