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Topical Area: Aging and Chronic Disease

Aging and Chronic Disease (Poster Session)

(P23-070-23) Improvement of Glycemic Control Through Long-Term Subcutaneous Administration of Insparin Nanoparticles in Diabetic Mice

Monday, July 24, 2023
12:45 PM – 1:45 PM ET
Location: Poster Board 66
Disclosure(s):
Md Abu Bakkar Siddik, PhD: No relevant financial relationship(s) with ineligible companies to disclose.
Nikhil V. Dhurandhar, LCEH, MS. PhD, FTOS: Borealis Foods: Grant/Research Support (Ongoing)
Indiana University Foundation: Grant/Research Support (Ongoing)
Insparin Therapeutics: Grant/Research Support (Ongoing); Ownership Interest (Ongoing)
International Egg Commission: Advisory Committee/Board Member (Ongoing)
Medifast: Advisory Committee/Board Member (Ongoing)
Metabologix/ Obthera: Consultant (Ongoing)
National Cattleman's Beef Association: Grant/Research Support (Terminated)
Novo Nordisk: Grant/Research Support (Terminated)
Springer Nature: Advisory Committee/Board Member (Ongoing)


Objectives: Most anti-diabetes drugs require insulin signaling for their action. However, insulin signaling is often impaired in diabetes. Hence, an agent that improves hyperglycemia independent of insulin signaling may be more effective. Transgenic or vector-mediated expression of adenovirus36-derived E4orf1 protein (Insparin) enhances glucose disposal independent of insulin in cells and rodent. Insparin spares endogenous insulin by reducing its need for glucose disposal. For clinically suitable delivery of Insparin, we developed liposomal nanoparticles (NP). Subcutaneous (SC) delivery of Insparin-NP in mice reproducibly enhances blood glucose clearance, as determined by the Glucose Tolerance Test (GTT) 24 h post injection. While the results are important, a sustained improvement in glycemic control is needed for diabetes treatment. Here, we tested if the long-term daily dose of Insparin-NP will provide sustained glycemic improvement as determined by blood HbA1c.

Methods: Insparin containing or void-NP were prepared using soy phosphatidylcholine. 14-16 wks old C57BL/6J mice fed a 45% HFD for 8-wks were divided into a control (CON) and a treatment (TRT) group, matched for body weights and HbA1c. The groups received daily SC injections of void-NP (CON) or 145 ug Insparin-NP (TRT), for 7-wks (43 doses). GTT, corresponding insulin and HbA1c were determined. Post-sacrifice, adverse effects if any of NP treatment on organ pathology were assessed.

Results: Baseline GTT, insulin, or HbA1c did not differ significantly between groups. After 7-wks, TRT group had significantly faster glucose clearance and significantly lower endogenous insulin requirement. HbA1c changed from 5.14 to 5.12 in 4 wks and to 5.53 in 7 wks for the CON group. At these timepoints, HbA1c changed from 5.14 to 4.91 and to 5.01 for the TRT group. HbA1c at 4 and 7 wks were significantly lower for the TRT group vs CON (p < 0.02 and p < 0.004). No adverse pathology was revealed in the liver, kidney, pancreas, heart, or skin, due to Insparin-NP.

Conclusions: Daily long-term Insparin administration led to sustained improvement in glycemic control in mice, despite continued HFD, and without overt pathological changes. These findings support further studies to evaluate the potential of Insparin as a novel anti-diabetes agent, for human trials.

Funding Sources: Insparin Inc.