(P01-16-26) Insparin Enhances Glucose Clearance Independent of Fasting Status in Mice

Objectives: Insparin, a 125 aa protein derived from human adenovirus 36 (Ad36) shows promise as an antidiabetic agent for humans. It promotes faster glucose clearance in response to a glucose tolerance test (GTT) in mice fasted for 4 - 6 h. However, to control hyperglycemia throughout the day, it is important to determine if Insparin promotes glucose clearance under non-fasting conditions as well. Here we conducted GTT in mice under fasting and non-fasting conditions post Insparin treatment or in control mice unexposed to Insparin.

Methods: 20 C57BL/6 male mice on high-fat diet for 11 weeks were treated with nanoliposome containing Insparin (145 µg, or 0 µg; N = 10 each), via subcutaneous injection 17 hours prior to GTT. Mice were divided into four groups of 5 mice each- Void and Insparin on 4 hour fasting; Void and Insparin on non-fasting condition. Following the 4-hour fasting, all mice were challenged with 2g/kg body weight glucose and blood glucose was measured at 0, 15, 30, 60 and 120 mins post glucose challenge.

Results: Insparin under both fasting and non-fasting conditions cleared glucose rapidly with a significantly lower area under the curve (p < 0.005) as compared to the Void; however, the difference was pronounced in the fasting group. Between group comparisons for fasting vs non-fasting did not show any significant difference for Insparin.

Conclusions: The glucose clearance potential of Insparin is strong under both fasting and non-fasting conditions. This supports practical utility of Insparin as a potential anti-diabetic agent in humans in fasted as well as fed state.

Funding Sources: Insparin Therapeutics