Session: FP02-Obesity and Diabetes: Drugs & Interventions
Room 303 (Moscone Center)
Poster Board SAT-786
Aim and methods: To further explore the insulin sensitizing influence of [D-Leu-4]-OB3, we compared the effects of metformin and [D-Leu-4]-OB3 on energy balance and glycemic control in streptozotocin (STZ)-induced diabetic (insulin-deficient) male Swiss Webster (SW) mice. Diabetic SW mice were given insulin (Levemir®, sc), either alone or in combination with metformin (200 mg/kg) or [D-Leu-4]-OB3 (40 mg/kg) orally in DDM, for 14 days. Body weight gain, and food and water intake were measured daily. Blood glucose levels were determined at the beginning of the study, and every other day thereafter. Serum was prepared from whole blood on day 15, and C-peptide concentrations were determined by ELISA.
Results: Insulin-deficient male SW mice given insulin alone for 14 days gained significantly (p < 0.001) more weight than DDM-treated control mice, or mice given insulin in combination with metformin or [D-Leu-4]-OB3. Mice receiving metformin and [D-Leu-4]-OB3 together were two grams (p < 0.001) lighter. The weight gain seen in mice given insulin alone was accompanied by significant increases in both food (p< 0.05) and water intake (p < 0.001). Mice treated with insulin in combination with metformin or [D-Leu-4]-OB3, or with metformin and [D-Leu-4]-OB3, consumed significantly less food (p < 0.05) and water (p < 0.05). Blood glucose levels in mice receiving insulin alone were reduced to 65.3% (p < 0.05) of initial levels, while mice receiving insulin with metformin or [D-Leu-4]-OB3 were reduced to 44.5% (p < 0.001) and 38.9% (p < 0.001) of initial levels, respectively.
Conclusions: Our results indicate that [D-Leu-4]-OB3 is as effective as metformin in preventing the body weight gain associated with insulin therapy, and in reducing blood glucose levels. They further indicate that [D-Leu-4]-OB3, on a molar basis, may be as efficient or surpass metformin as an insulin sensitizer, and suggest the possibility that this peptide may have potential application to the management of both T1DM and T2DM in humans.
Nothing to Disclose: ZMN, MCL, PG
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