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    Amino Acid Nanofibers Improve Glycemia and Confer Cognitive Therapeutic Efficacy to Bound Insulin

    Journal: Pharmaceutics, Volume 14, JAN

    Authors: Lee, Aejin; Mason, McKensie L.; Lin, Tao; Kumar, Shashi Bhushan; Kowdley, Devan; Leung, Jacob H.; Muhanna, Danah; Sun, Yuan; Ortega-Anaya, Joana; Yu, Lianbo; Fitzgerald, Julie; DeVries, A. Courtney; Nelson, Randy J.; Weil, Zachary M.; Jimenez-Flores, Rafael; Parquette, Jon R.; Ziouzenkova, Ouliana

    Keywords: diabetes; leptin; nanofibers; taurine

    Diabetes poses a high risk for debilitating complications in neural tissues, regulating glucose uptake through insulin-dependent and predominantly insulin-independent pathways. Supramolecular nanostructures provide a flexible strategy for combinatorial regulation of glycemia. Here, we compare the effects of free insulin to insulin bound to positively charged nanofibers comprised of self-assembling amino acid compounds (AACs) with an antioxidant-modified side chain moiety (AAC2) in both in vitro and in vivo models of type 1 diabetes. Free AAC2, free human insulin (hINS) and AAC2-bound-human insulin (AAC2-hINS) were tested in streptozotocin (STZ)-induced mouse model of type 1 diabetes. AAC2-hINS acted as a complex and exhibited different properties compared to free AAC2 or hINS. Mice treated with the AAC2-hINS complex were devoid of hypoglycemic episodes, had improved levels of insulin in circulation and in the brain, and increased expression of neurotransmitter taurine transporter, Slc6a6. Consequently, treatment with AAC2-hINS markedly advanced both physical and cognitive performance in mice with STZ-induced and genetic type 1 diabetes compared to treatments with free AAC2 or hINS. This study demonstrates that the flexible nanofiber AAC2 can serve as a therapeutic platform for the combinatorial treatment of diabetes and its complications.
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