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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intranasal
  • Animals
  • Biological Availability
  • Blood Glucose / drug effects*
  • Energy Metabolism / drug effects*
  • Insulin / metabolism*
  • Insulin Secretion
  • Leptin / administration & dosage
  • Leptin / pharmacokinetics*
  • Leptin / pharmacology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Obese
  • Osteogenesis / drug effects*
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / pharmacokinetics
  • Peptide Fragments / pharmacology*


  • Blood Glucose
  • Insulin
  • Leptin
  • Peptide Fragments
  • leptin (116-130)