Background: We have recently shown that intranasal administration of mouse [D‐Leu‐4]‐OB3 reconstituted in Intravail® 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® 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® alone or mouse [D‐Leu‐4]‐OB3 in Intravail® 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® alone. Mouse [D‐Leu‐4]‐OB3 elevated serum osteocalcin in db/db mice by 28.7% over Intravail® treated control mice.
Conclusions: The results of our study indicate that intranasal delivery of biologically active mouse [D‐Leu‐4]‐OB3 in Intravail® 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.