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Diabetes Obes Metab. 2010 Oct;12(10):871-5. doi: 10.1111/j.1463-1326.2010.01243.x.

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.

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1
Department of Medicine, Division of Endocrinology and Metabolism, Albany Medical College, Albany, NY, USA.

Abstract

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.

[Indexed for MEDLINE]

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