NDLI: The effects of age on uptake, serum half-life and bioavailability of mouse [D-Leu-4]OB3, a synthetic peptide amide with leptin-like activity, in male C57BL/6J mice.

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The effects of age on uptake, serum half-life and bioavailability of mouse [D-Leu-4]OB3, a synthetic peptide amide with leptin-like activity, in male C57BL/6J mice.

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The effects of age on uptake, serum half-life and bioavailability of mouse [D-Leu-4]OB3, a synthetic peptide amide with leptin-like activity, in male C57BL/6J mice.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Lee, Daniel W. Leinung, Matthew C. Grasso, Patricia
Description	Country affiliation: United States Author Affiliation: Lee DW ( Department of Medicine, Division of Endocrinology and Metabolism, MC 141, Albany Medical College, Albany, NY 12208, USA.)
Abstract	We have previously shown that the activity of a synthetic peptide amide corresponding to amino acid residues 116-130 of mouse leptin is contained in a restricted sequence at the amino terminus of the peptide, between residues 116 and 122 (Ser-Cys-Ser-Leu-Pro-Glu-Thr). This peptide was named mouse OB3. The potency of OB3 was improved by replacing the L-leucine residue at position four with its D-isomer. Intraperitoneal administration (i.p.) of mouse OB3 or [D-Leu-4]OB3 to ob/ob and db/db mice reduces food intake, body weight gain and serum glucose levels, and enhances insulin sensitivity. These effects of OB3 and [D-Leu-4]OB3 are very pronounced in young mice and diminish with age. In the present study, we measured uptake, serum half-life, and bioavailability of mouse [D-Leu-4]OB3 in mice of different ages. Groups of male C57BL/6J mice, six and 25 weeks of age, were given a single i.p. injection of 1 mg mouse [D-Leu-4]OB3 in PBS. Five, 10, 20, 40, 60, 120, or 180 min after injection, the mice were anesthetized and exsanguinated. Serum samples were prepared and assayed for mouse [D-Leu-4]OB3 content by competitive ELISA. In six week-old mice, the maximum concentration of mouse [D-Leu-4]OB3 was reached in 10 min, and the serum half-life was approximately 52.5 min. In 25 week-old mice, however, mouse [D-Leu-4]OB3 peaked in 5 min, and the serum half-life was approximately 30.6 min. The relative bioavailability of mouse [D-Leu-4]OB3 in six and 25 week-old mice was determined by measuring the area under the uptake curves. Bioavailability of mouse [D-Leu-4]OB3 was approximately 20% greater in six week-old mice than in 25 week-old mice. The results of this study indicate that at least some pharmacokinetic parameters of peptide uptake change as mice age. They also suggest that differences in uptake, serum half-life, and relative bioavailability of mouse [D-Leu-4]OB3 may contribute, at least in part, to the reduced efficacy of bioactive leptin-related peptides we have consistently observed in ob/ob and db/db mice as they age.
File Format	HTM / HTML
ISSN	01670115
Issue Number	1-3
Volume Number	150
e-ISSN	18731686
Journal	Regulatory Peptides
Language	English
Publisher	Elsevier
Publisher Date	2008-10-09
Publisher Place	Netherlands
Access Restriction	Subscribed
Subject Keyword	Discipline Biochemistry Aging Physiology Leptin Agonists Pharmacokinetics Peptide Fragments Animals Area Under Curve Biological Availability Body Weight Drug Effects Enzyme-linked Immunosorbent Assay Half-life Injections, Intraperitoneal Administration & Dosage Male Metabolic Clearance Rate Mice Mice, Inbred C57bl Stereoisomerism Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject Domain (in MeSH)	Eukaryota Pathological Conditions, Signs and Symptoms Hormones, Hormone Substitutes, and Hormone Antagonists Amino Acids, Peptides, and Proteins Diagnosis Therapeutics Investigative Techniques Physical Phenomena Chemical Phenomena Metabolism Physiological Phenomena

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The effects of age on uptake, serum half-life and bioavailability of mouse [D-Leu-4]OB3, a synthetic peptide amide with leptin-like activity, in male C57BL/6J mice.

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