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Peptides. 2013 May;43:167-73. doi: 10.1016/j.peptides.2013.02.023. Epub 2013 Mar 7.

[D-Leu-4]-OB3, an orally bioavailable leptin-related synthetic peptide insulin sensitizer: a study comparing the efficacies of [D-Leu-4]-OB3 and metformin on energy balance and glycemic regulation in insulin-deficient male Swiss Webster mice.

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1
Department of Medicine, Division of Endocrinology and Metabolism, Albany Medical College, Albany, NY 12208, USA.

Abstract

The effects of oral delivery of exenatide or pramlintide acetate in dodecyl maltoside (DDM) on energy balance and glycemic control in insulin-resistant obese db/db mice are enhanced when given in combination with [D-Leu-4]-OB3. To examine the anti-hyperglycemic influence of [D-Leu-4]-OB3 in a non-obese insulin-deficient animal model, we compared the effects of metformin (200mg/kg) and [D-Leu-4]-OB3 (40 mg/kg) on energy balance and glycemic control in streptozotocin (STZ)-induced diabetic male Swiss Webster (SW) mice. Diabetic mice were given insulin (Levemir(®), sc) alone, or in combination with metformin or [D-Leu-4]-OB3 orally in DDM, for 14 days. Body weight and food and water intake were measured daily. Fasting blood glucose levels were determined every other day. Serum C-peptide was measured by ELISA. Diabetic mice receiving insulin alone for 14 days gained significantly more weight than DDM-treated control mice, or mice given insulin in combination with metformin or [D-Leu-4]-OB3. The weight gain seen in mice given insulin alone was accompanied by significant increases in both food and water intake. Mice treated with insulin in combination with metformin or [D-Leu-4]-OB3, consumed significantly less food and water. Blood glucose levels in STZ-treated mice receiving insulin alone were reduced to 65.3% of initial levels, while mice receiving insulin with metformin or [D-Leu-4]-OB3 were reduced to 44.5% and 38.9%, respectively. Our results indicate that [D-Leu-4]-OB3 is as effective as metformin in preventing the body weight gain associated with insulin therapy, and on a molar basis, that the efficacy of [D-Leu-4]-OB3 as an insulin sensitizer may equal or surpass that of metformin.

PMID:
23500518
DOI:
10.1016/j.peptides.2013.02.023
[Indexed for MEDLINE]

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