Intranasal delivery of mouse (D-Leu-4)-OB3, a synthetic peptide amide with leptin-like activity, improves energy balance, glycaemic control, insulin sensitivity and bone formation in leptin-resistant C57BLK/6-m db/db mice.

摘要

BACKGROUND: We have recently shown that intranasal administration of mouse [D-Leu-4]-OB3 reconstituted in Intravail((R)) to male Swiss Webster mice resulted in significantly higher uptake and bioavailability when compared with commonly used injection methods of delivery. AIM AND METHODS: In this study, we examined the effects of intranasal delivery of mouse [D-Leu-4]-OB3 in Intravail((R)) on energy balance, glucose regulation, insulin secretion and serum levels of osteocalcin, a specific and sensitive marker of bone formation. Genetically obese C57BLK/6-m db/db mice were allowed food and water ad libitum and given either Intravail((R)) alone or mouse [D-Leu-4]-OB3 in Intravail((R)) for 14 days by intranasal instillation. RESULTS: Mouse [D-Leu-4]-OB3 reduced body weight gain, daily food intake, daily water intake and serum glucose by 11.5, 2.2, 4.0 and 61.9%, respectively. Serum insulin levels in db/db mice given mouse [D-Leu-4]-OB3 were approximately threefold lower than those in mice receiving Intravail((R)) alone. Mouse [D-Leu-4]-OB3 elevated serum osteocalcin in db/db mice by 28.7% over Intravail((R)) treated control mice. CONCLUSIONS: The results of our study indicate that intranasal delivery of biologically active mouse [D-Leu-4]-OB3 in Intravail((R)) is feasible and has significant effects on regulating body weight gain, food and water intake, serum glucose, insulin sensitivity and bone formation in leptin-resistant C57BLK/6-m db/db mice.