1. Amino Acid Nanofibers Improve Glycemia and Confer Cognitive Therapeutic Efficacy to Bound Insulin.
- Author
-
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., Jiménez-Flores, Rafael, Parquette, Jon R., and Ziouzenkova, Ouliana
- Subjects
- *
INSULIN , *AMINO acids , *TYPE 1 diabetes , *TREATMENT effectiveness , *NANOFIBERS , *AMINO compounds , *HYPERGLYCEMIA - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF