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Article

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

1
Department of Human Sciences, The Ohio State University, Columbus, OH 43210, USA
2
Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210, USA
3
Department of Food Science and Technology, The Ohio State University, Columbus, OH 43210, USA
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Department of Biomedical Informatics, The Ohio State University, Columbus, OH 43210, USA
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Department of Neuroscience, The Ohio State University, Columbus, OH 43210, USA
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Department of Neuroscience, West Virginia University, Morgantown, WV 26506, USA
7
Rockefeller Neuroscience Institute, West Virginia University, Morgantown, WV 26506, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Dong Kwon Yang
Pharmaceutics 2022, 14(1), 81; https://doi.org/10.3390/pharmaceutics14010081
Received: 22 November 2021 / Revised: 19 December 2021 / Accepted: 23 December 2021 / Published: 29 December 2021
(This article belongs to the Topic Animal Model in Biomedical Research)
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. View Full-Text
Keywords: diabetes; leptin; nanofibers; taurine diabetes; leptin; nanofibers; taurine
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MDPI and ACS Style

Lee, A.; Mason, M.L.; Lin, T.; Kumar, S.B.; Kowdley, D.; Leung, J.H.; Muhanna, D.; Sun, Y.; Ortega-Anaya, J.; Yu, L.; Fitzgerald, J.; DeVries, A.C.; Nelson, R.J.; Weil, Z.M.; Jiménez-Flores, R.; Parquette, J.R.; Ziouzenkova, O. Amino Acid Nanofibers Improve Glycemia and Confer Cognitive Therapeutic Efficacy to Bound Insulin. Pharmaceutics 2022, 14, 81. https://doi.org/10.3390/pharmaceutics14010081

AMA Style

Lee A, Mason ML, Lin T, Kumar SB, Kowdley D, Leung JH, Muhanna D, Sun Y, Ortega-Anaya J, Yu L, Fitzgerald J, DeVries AC, Nelson RJ, Weil ZM, Jiménez-Flores R, Parquette JR, Ziouzenkova O. Amino Acid Nanofibers Improve Glycemia and Confer Cognitive Therapeutic Efficacy to Bound Insulin. Pharmaceutics. 2022; 14(1):81. https://doi.org/10.3390/pharmaceutics14010081

Chicago/Turabian Style

Lee, Aejin, McKensie L. Mason, Tao Lin, Shashi B. Kumar, Devan Kowdley, Jacob H. Leung, Danah Muhanna, Yuan Sun, Joana Ortega-Anaya, Lianbo Yu, Julie Fitzgerald, A. C. DeVries, Randy J. Nelson, Zachary M. Weil, Rafael Jiménez-Flores, Jon R. Parquette, and Ouliana Ziouzenkova. 2022. "Amino Acid Nanofibers Improve Glycemia and Confer Cognitive Therapeutic Efficacy to Bound Insulin" Pharmaceutics 14, no. 1: 81. https://doi.org/10.3390/pharmaceutics14010081

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