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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
Author(s) -
Waldrop M. A.,
Leinung M. C.,
Lee D. W.,
Grasso P.
Publication year - 2010
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/j.1463-1326.2010.01243.x
Subject(s) - leptin , insulin , endocrinology , medicine , nasal administration , insulin sensitivity , energy balance , insulin resistance , balance (ability) , obesity , biology , pharmacology , physical therapy , ecology
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.