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Analysis of Insulin Analogs and the Strategy of Their Further Development

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Abstract

We analyzed the structural properties of the peptide hormone insulin and described the mechanism of its physiological action, as well as effects of insulin in type 1 and 2 diabetes. Recently published data on the development of novel insulin preparations based on combining molecular design and genetic engineering approaches are presented. New strategies for creation of long-acting insulin analogs, the mechanisms of functioning of these analogs and their structure are discussed. Side effects of insulin preparations are described, including amyloidogenesis and possible mitogenic effect. The pathways for development of novel insulin analogs are outlined with regard to the current requirements for therapeutic preparations due to the wider occurrence of diabetes of both types.

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Abbreviations

αCT:

C-terminal domain of insulin receptor α-subunit

BMI:

body mass index

ER:

endoplasmic reticulum

IR:

insulin receptor

IGF-1R:

type 1 insulin-like growth factor receptor

IRA:

insulin receptor isoform A

IRB:

nsulin receptor isoform B

L1:

leucine-rich repeat domain of the insulin receptor α-subunit

NPH:

neutral protamine Hagedorn

PEG:

polyethylene glycol

ThT:

thioflavin T

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Authors and Affiliations

  1. Institute of Protein Research, Russian Academy of Sciences, 142290, Pushchino, Moscow Region, Russia

    O. M. Selivanova, S. Yu. Grishin, A. V. Glyakina & O. V. Galzitskaya

  2. Lomonosov Moscow State University, 119991, Moscow, Russia

    S. Yu. Grishin

  3. Institute of Mathematical Problems of Biology, Keldysh Institute of Applied Mathematics, Russian Academy of Sciences, 142290, Pushchino, Moscow Region, Russia

    A. V. Glyakina

  4. Joint-Stock Scientific Production Association Bioran, 119261, Moscow, Russia

    A. S. Sadgyan & N. I. Ushakova

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Original Russian Text © O. M. Selivanova, S. Yu. Grishin, A. V. Glyakina, A. S. Sadgyan, N. I. Ushakova, O. V. Galzitskaya, 2018, published in Uspekhi Biologicheskoi Khimii, 2018, Vol. 58, pp. 313–346.

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Selivanova, O.M., Grishin, S.Y., Glyakina, A.V. et al. Analysis of Insulin Analogs and the Strategy of Their Further Development. Biochemistry Moscow 83 (Suppl 1), S146–S162 (2018). https://doi.org/10.1134/S0006297918140122

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