The earliest study to utilise apelin analogues in diabetes therapy employed an adeno-associated virus minigene system to mimic systemic expression of apelin-13, apelin-36 and modified analogues of apelin-36, namely apelin-36(L28A) where Leu28 was substituted by Ala.28,86 BDF mice were administered 5 × 1011 genome copies of an apelin-expressing adeno-associated virus via tail vein injection and placed onto a high-fat diet for 8 weeks. Here, APLN is linked to diabetes mellitus.