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.
Similar content being viewed by others
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
References
Banting, F. G., and Best, C. J. (1922) The internal secretion of the pancreas, Reprinted in 1972, Vol. 80, to mark 50th anniversary of the discovery, J. Lab. Clin. Med., 7, 251–266.
De Meyts, P. (2004) Insulin and its receptor: structure, function and evolution, Bioessays, 26, 1351–1362.
Cabrera, S. M., Chen, Y. G., Hagopian, W. A., and Hessner, M. J. (2016) Blood-based signatures in type 1 diabetes, Diabetologia, 59, 414–425.
Edelman, S., and Pettus, J. (2014) Challenges associated with insulin therapy in type 2 diabetes mellitus, Am. J. Med., 127, 11–16.
Tkachuk, V. A., and Vorotnikov, A. V. (2014) Molecular mechanisms of development of insulin resistance, Saharnii Diabet, 2, 29–40.
Titov, V. N. (2012) Phylogenesis, etiology and pathogenesis of insulin resistance. Differences from type ii diabetes mellitus, Vestnik RAMN, 4, 65–73.
American Diabetes Association (2012) Diagnosis and classification of diabetes mellitus, Diabetes Care, 35 (Suppl. 1), 64-71.
Chin, J. A., and Sumpio, B. E. (2014) Diabetes mellitus and peripheral vascular disease: diagnosis and management, Clin. Podiatr. Med. Surg., 31, 11–26.
Todd, J. A. (1990) Genetic control of autoimmunity in type 1 diabetes, Immunol. Today, 11, 122–129.
Redondo, M. J., Fain, P. R., and Eisenbarth, G. S. (2001) Genetics of type 1A diabetes, Recent Prog. Horm. Res., 56, 69–89.
Ohtsubo, K., Chen, M. Z., Olefsky, J. M., and Marth, J. D. (2011) Pathway to diabetes through attenuation of pancreatic beta cell glycosylation and glucose transport, Nat. Med., 17, 1067–1075.
Ye, J. (2013) Mechanisms of insulin resistance in obesity, Front. Med., 7, 14–24.
Chakraborty, C., Doss, C. G. P., Bandyopadhyay, S., and Agoramoorthy, G. (2014) Influence of miRNA in insulin signaling pathway and insulin resistance: micromolecules with a major role in type-2 diabetes, Wiley Interdiscip. Rev. RNA, 5, 697–712.
Feng, X., Tang, H., Leng, J., and Jiang, Q. (2014) Suppressors of cytokine signaling (SOCS) and type 2 diabetes, Mol. Biol. Rep., 41, 2265–2274.
Cheng, K., Andrikopoulos, S., and Gunton, J. E. (2013) First phase insulin secretion and type 2 diabetes, Curr. Mol. Med., 13, 126–139.
Zaykov, A. N., Mayer, J. P., and DiMarchi, R. D. (2016) Pursuit of a perfect insulin, Nat. Rev. Drug Discov., 15, 425–439.
Home, P., Riddle, M., Cefalu, W. T., Bailey, C. J., Bretzel, R. G., Del Prato, S., Leroith, D., Schernthaner, G., Van Gaal, L., and Raz, I. (2014) Insulin therapy in people with type 2 diabetes: opportunities and challenges? Diabetes Care, 37, 1499–1508.
Dzhavakhishvili, T. S., Romantsova, T. I., and Roik, O. V. (2010) Dynamics of body weight in patients with type 2 diabetes during the first year of insulin therapy, Obes. Metab., 4, 13–19.
Dedov, I. I., Shestakova, M. V., and Moiseev, S. V. (2005) Analogues of insulin, Klin. Farmakol. Ter., 14, 49–55.
Vigneri, R., Squatrito, S., and Sciacca, L. (2010) Insulin and its analogs: actions via insulin and IGF receptors, Acta Diabetol., 47, 271–278.
Bell, G. I., Pictet, R. L., Rutter, W. J., Cordell, B., Tischer, E., and Goodman, H. M. (1980) Sequence of the human insulin gene, Nature, 284, 26–32.
Alarcyn, C., Leahy, J. L., Schuppin, G. T., and Rhodes, C. J. (1995) Increased secretory demand rather than a defect in the proinsulin conversion mechanism causes hyper-proinsulinemia in a glucose-infusion rat model of noninsulin-dependent diabetes mellitus, J. Clin. Invest., 95, 1032–1039.
Greider, M. H., Howell, S. L., and Lacy, P. E. (1969) Isolation and properties of secretory granules from rat islets of Langerhans. II. Ultrastructure of the beta granule, J. Cell Biol., 41, 162–166.
Michael, J., Carroll, R., Swift, H. H., and Steiner, D. F. (1987) Studies on the molecular organization of rat insulin secretory granules, J. Biol. Chem., 262, 16531–16535.
Chang, T. W., and Goldberg, A. L. (1978) The metabolic fates of amino acids and the formation of glutamine in skeletal muscle, J. Biol. Chem., 253, 3685–3693.
Eto, K., Tsubamoto, Y., Terauchi, Y., Sugiyama, T., Kishimoto, T., Takahashi, N., Yamauchi, N., Kubota, N., Murayama, S., Aizawa, T., Akanuma, Y., Aizawa, S., Kasai, H., Yazaki, Y., and Kadowaki, T. (1999) Role of NADH shuttle system in glucose-induced activation of mitochon-drial metabolism and insulin secretion, Science, 283, 981–985.
Bender, K., Newsholme, P., Brennan, L., and Maechler, P. (2006) The importance of redox shuttles to pancreatic beta-cell energy metabolism and function, Biochem. Soc. Trans., 34, 811–814.
Nolan, C. J., Leahy, J. L., Delghingaro-Augusto, V., Moibi, J., Soni, K., Peyot, M. L., Fortier, M., Guay, C., Lamontagne, J., Barbeau, A., Przybytkowski, E., Joly, E., Masiello, P., Wang, S., Mitchell, G. A., and Prentki, M. (2006) Beta cell compensation for insulin resistance in Zucker fatty rats: increased lipolysis and fatty acid signalling, Diabetologia, 49, 2120–2130.
Prentki, M., Joly, E., El-Assaad, W., and Roduit, R. (2002) Malonyl-CoA signaling, lipid partitioning, and glucolipo-toxicity: role in beta-cell adaptation and failure in the etiology of diabetes, Diabetes, 51 (Suppl. 3), 405–413.
Baker, E. N., Blundell, T. L., Cutfield, J. F., Cutfield, S. M., Dodson, E. J., Dodson, G. G., Hodgkin, D. M., Hubbard, R. E., Isaacs, N. W., and Reynolds, C. D. (1988) The structure of 2Zn pig insulin crystals at 1.5 Å resolution, Philos. Trans. R. Soc. Lond. B Biol. Sci., 319, 369–456.
Wood, S. P., Blundell, T. L., Wollmer, A., Lazarus, N. R., and Neville, R. W. (1975) The relation of conformation and association of insulin to receptor binding; X-ray and circular-dichroism studies on bovine and hystricomorph insulins, Eur. J. Biochem., 55, 531–542.
Williamson, K. L., and Williams, R. J. (1979) Conformational analysis by nuclear magnetic resonance: insulin, Biochemistry, 18, 5966–5972.
Ramesh, V., and Bradbury, J. H. (1987) 1H NMR studies of insulin: histidine residues, metal binding, and dissociation in alkaline solution, Arch. Biochem. Biophys., 258, 112–122.
Wollmer, A., Rannefeld, B., Johansen, B. R., Hejnaes, K. R., Balschmidt, P., and Hansen, F. B. (1987) Phenolpromoted structural transformation of insulin in solution, Biol. Chem. Hoppe. Seyler., 368, 903–911.
Pittman, I., and Tager, H. S. (1995) A spectroscopic investigation of the conformational dynamics of insulin in solution, Biochemistry, 34, 10578–10590.
Bakaysa, D. L., Radziuk, J., Havel, H. A., Brader, M. L., Li, S., Dodd, S. W., Beals, J. M., Pekar, A. H., and Brems, D. N. (1996) Physicochemical basis for the rapid time-action of LysB28ProB29-insulin: dissociation of a protein–ligand complex, Protein Sci., 5, 2521–2531.
De Meyts, P., and Whittaker, J. (2002) Structural biology of insulin and IGF1 receptors: implications for drug design, Nat. Rev. Drug Discov., 1, 769–783.
Menting, J. G., Whittaker, J., Margetts, M. B., Whittaker, L. J., Kong, G. K., Smith, B. J., Watson, C. J., Zakova, L., KletvHkova, E., Jiracek, J., Chan, S. J., Steiner, D. F., Dodson, G. G., Brzozowski, A. M., Weiss, M. A., Ward, C. W., and Lawrence, M. C. (2013) How insulin engages its primary binding site on the insulin receptor, Nature, 493, 241–245.
Menting, J. G., Yang, Y., Chan, S. J., Phillips, N. B., Smith, B. J., Whittaker, J., Wickramasinghe, N. P., Whittaker, L. J., Pandyarajan, V., Wan, Z. L., Yadav, S. P., Carroll, J. M., Strokes, N., Roberts, C. T., Jr., Ismail-Beigi, F., Milewski, W., Steiner, D. F., Chauhan, V. S., Ward, C. W., Weiss, M. A., and Lawrence, M. C. (2014) Protective hinge in insulin opens to enable its receptor engagement, Proc. Natl. Acad. Sci. USA, 111, 3395–3404.
Pandyarajan, V., Smith, B. J., Phillips, N. B., Whittaker, L., Cox, G. P., Wickramasinghe, N., Menting, J. G., Wan, Z. L., Whittaker, J., Ismail-Beigi, F., Lawrence, M. C., and Weiss, M. A. (2014) Aromatic anchor at an invariant hormonereceptor interface, J. Biol. Chem., 289, 34709–34727.
Pullen, R. A., Lindsay, D. G., Wood, S. P., Tickle, I. J., Blundell, T. L., Wollmer, A., Krail, G., Brandenburg, D., Zahn, H., Gliemann, J., and Gammeltoft, S. (1976) Receptor-binding region of insulin, Nature, 259, 369–373.
Kwok, S. C., Steiner, D. F., Rubenstein, A. H., and Tager, H. S. (1983) Identification of a point mutation in the human insulin gene giving rise to a structurally abnormal insulin (insulin Chicago), Diabetes, 32, 872–875.
Shoelson, S., Haneda, M., Blix, P., Nanjo, A., Sanke, T., Inouye, K., Steiner, D., Rubenstein, A., and Tager, H. (1983) Three mutant insulins in man, Nature, 302, 540–543.
Shoelson, S., Fickova, M., Haneda, M., Nahum, A., Musso, G., Kaiser, E. T., Rubenstein, A. H., and Tager, H. (1983) Identification of a mutant human insulin predicted to contain a serine-for-phenylalanine substitution, Proc. Natl. Acad. Sci. USA, 80, 7390–7394.
Kobayashi, M., Ohgaku, S., Iwasaki, M., Maegawa, H., Shigeta, Y., and Inouye, K. (1982) Supernormal insulin: [D-PheB24]-insulin with increased affinity for insulin receptors, Biochem. Biophys. Res. Commun., 107, 329–336.
Nanjo, K., Sanke, T., Miyano, M., Okai, K., Sowa, R., Kondo, M., Nishimura, S., Iwo, K., Miyamura, K., and Given, B. D. (1986) Diabetes due to secretion of a structurally abnormal insulin (insulin Wakayama). Clinical and functional characteristics of [LeuA3] insulin, J. Clin. Invest., 77, 514–519.
Blundell, T. L., Cutfield, J. F., Cutfield, S. M., Dodson, E. J., Dodson, G. G., Hodgkin, D. C., and Mercola, D. A. (1972) Three-dimensional atomic structure of insulin and its relationship to activity, Diabetes, 21, 492–505.
Cosmatos, A., Cheng, K., Okada, Y., and Katsoyannis, P. G. (1978) The chemical synthesis and biological evaluation of [1-L-alanine-A]-and [1-D-alanine-A] insulins, J. Biol. Chem., 253, 6586–6590.
Geiger, R., Geisen, K., Summ, H. D., and Langer, D. (1975) (A1-D-alanine) insulin, Hoppe. Seylers. Z. Physiol. Chem., 356, 1635–1649.
Geiger, R., Geisen, K., and Summ, H. D. (1982) Exchange of A1-glycine in bovine insulin with L-and D-tryptophan, Hoppe. Seylers. Z. Physiol. Chem., 363, 1231–1239.
Nakagawa, S. H., and Tager, H. S. (1989) Perturbation of insulin–receptor interactions by intramolecular hormone cross-linking. Analysis of relative movement among residues A1, B1, and B29, J. Biol. Chem., 264, 272–279.
Ogawa, H., Burke, G. T., Chanley, J. D., and Katsoyannis, P. G. (1987) Effect of N-methylation of selected peptide bonds on the biological activity of insulin. [2-N-methylisoleucine-A]insulin and [3-N-methylvaline-A]insulin, Int. J. Pept. Protein Res., 30, 460–473.
Schwartz, G., and Katsoyannis, P. G. (1978) Synthesis of des(tetrapeptide B(1-4)) and des(pentapeptide B(1-5)) human insulins. Two biologically active analogues, Biochemistry, 17, 4550–4556.
Nakagawa, S. H., and Tager, H. S. (1991) Implications of invariant residue LeuB6 in insulin–receptor interactions, J. Biol. Chem., 266, 11502–11509.
Schwartz, G. P., Burke, G. T., and Katsoyannis, P. G. (1987) A superactive insulin: [B10-aspartic acid]insulin(human), Proc. Natl. Acad. Sci. USA, 84, 6408–6411.
Chan, S. J., Seino, S., Gruppuso, P. A., Schwartz, R., and Steiner, D. F. (1987) A mutation in the B chain coding region is associated with impaired proinsulin conversion in a family with hyperproinsulinemia, Proc. Natl. Acad. Sci. USA, 84, 2194–2197.
Gruppuso, P. A., Gorden, P., Kahn, C. R., Cornblath, M., Zeller, W. P., and Schwartz, R. (1984) Familial hyperproin-sulinemia due to a proposed defect in conversion of proinsulin to insulin, N. Engl. J. Med., 311, 629–634.
Brange, J. Ribel, U., Hansen, J. F., Dodson, G., Hansen, M. T., Havelund, S., Melberg, S. G., Norris, F., Norris, K., and Snel, L. (1988) Monomeric insulins obtained by protein engineering and their medical implications, Nature, 333, 679–682.
Brems, D. N., Alter, L. A., Beckage, M. J., Chance, R. E., DiMarchi, R. D., Green, L. K., Long, H. B., Pekar, A. H., Shields, J. E., and Frank, B. H. (1992) Altering the association properties of insulin by amino acid replacement, Protein Eng., 5, 527–533.
Blundell, T. L., Cutfield, J. F., Cutfield, S. M., Dodson, E. J., Dodson, G. G., Hodgkin, D. C., and Mercola, D. A. (1972) Three-dimensional atomic structure of insulin and its relationship to activity, Diabetes, 21, 492–505.
Nathan, D. M., Genuth, S., Lachin, J., Cleary, P., Crofford, O., Davis, M., Rand, L., and Siebert, C. (1993) The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus, N. Engl. J. Med., 329, 977–986.
Chou, H. S., Larsson, M., Hsiao, M. H., Chen, Y. C., Roding, M., Nyden, M., and Liu, D. M. (2016) Injectable insulin-lysozyme-loaded nanogels with enzymatically-controlled degradation and release for basal insulin treatment: in vitro characterization and in vivo observation, J. Control. Release, 224, 33–42.
Ionova, T. I., Odin, V. I., Nikitina, T. P., Kurbatova, K. A., and Shablovskaya, N. E. (2013) Quality of life and problems posed by hypoglycemia in type 2 diabetes mellitus during oral hypoglycemic therapy, Klin. Med., 9, 34–40.
Hirsch, I. B., Farkas-Hirsch, R., and Skyler, J. S. (1990) Intensive insulin therapy for treatment of type I diabetes, Diabetes Care, 13, 1265–1283.
Gusarov, D. A., Gusarova, V. D., Bayramashvili, D. I., and Mironov, A. F. (2008) Human insulin and its pharmaceutical analogs, Biomed. Khim., 54, 624–642.
Home, P. D. (2012) The pharmacokinetics and pharmaco-dynamics of rapidacting insulin analogues and their clinical consequences, Diabetes Obes. Metab., 14, 780–788.
Oakley, W., Hill, D., and Oakley, N. (1966) Combined use of regular and crystalline protamine (NPH) insulins in the treatment of severe diabetes, Diabetes, 15, 219–222.
Rosenstock, J., Schwartz, S. L., Clark, C. M., Jr., Park, G. D., Donley, D. W., and Edwards, M. B. (2001) Basal insulin therapy in type 2 diabetes: 28-week comparison of insulin glargine (HOE 901) and NPH insulin, Diabetes Care, 24, 631–636.
Johnson, I. S. (1983) Human insulin from recombinant DNA technology, Science, 219, 632–637.
Peters, A. L., Pollom, R. D., Zielonka, J. S., Carey, M. A., and Edelman, S. V. (2015) Biosimilars and new insulin versions, Endocr. Pract., 21, 1387–1394.
Miroshnikov, A. I. (2009) Recipe for Russian insulin, Acta Naturae, 3, 18–20.
Owens, D. R., Landgraf, W., Schmidt, A., Bretzel, R. G., and Kuhlmann, M. K. (2012) The emergence of biosimilar insulin preparations–a cause for concern? Diabetes Technol. Ther., 14, 989–996.
Habriev, R. U. (2005) in Manual on Experimental (Preclinical) Study of New Pharmacological Substances (Habriev, R. U., ed.) [in Russian], Meditsina, Moscow.
Mironov, A. N. (2012) in Manual on Preclinical Trials of Medicines, Part I (Mironov, A. N., ed.) [in Russian], Grif i K, Moscow.
Mironov, A. N. (2013) in Manual on Expertise of Medicines, Part V. I. (Mironov, A. N., ed.) [in Russian], Grif i K, Moscow.
Atkinson, M. A., Eisenbarth, G. S., and Michels, A. W. (2014) Type 1 diabetes, Lancet, 383, 69–82.
Kuraeva, T. L. (2010) Analogues of insulin in achieving compensation and improving the quality of life of children and adolescents with type 1 diabetes mellitus, Saharnii Diabet, 3, 147–152.
Howey, D. C., Bowsher, R. R., Brunelle, R. L., and Woodworth, J. R. (1994) [Lys(B28), Pro(B29)]-human insulin. A rapidly absorbed analogue of human insulin, Diabetes, 43, 396–402.
Ciszak, E., Beals, J. M., Frank, B. H., Baker, J. C., Carter, N. D., and Smith, G. D. (1995) Role of C-terminal B-chain residues in insulin assembly: the structure of hexameric LysB28ProB29-human insulin, Structure, 3, 615–622.
Bakaysa, D. L., Radziuk, J., Havel, H. A., Brader, M. L., Li, S., Dodd, S. W., Beals, J. M., Pekar, A. H., and Brems, D. N. (1996) Physicochemical basis for the rapid time-action of Lys B28 Pro B29-insulin: dissociation of a protein–ligand complex, Protein Sci., 5, 2521–2531.
Becker, R. H. A., Frick, A. D., Burger, F., Potgieter, J. H., and Scholtz, H. (2005) Insulin glulisine, a new rapid-acting insulin analogue, displays a rapid time-action profile in obese nondiabetic subjects, Exp. Clin. Endocrinol. Diabetes, 113, 435–443.
Dreyer, M., Prager, R, Robinson, A., Busch, K., Ellis, G., Souhami, E., and Van Leendert, R. (2005) Efficacy and safety of insulin glulisine in patients with type 1 diabetes, Horm. Metab. Res., 37, 702–707.
Pavlova, M. G. (2008) Apidra (insulin glulisin) in the treatment of type 1 diabetes mellitus, Saharnii Diabet, 2, 65–68.
Heinemann, L., Heise, T., Wahl, L. C., Trautmann, M. E., Ampudia, J., Starke, A. A., and Berger, M. (1996) Prandial glycaemia after a carbohydrate-rich meal in type I diabetic patients: using the rapid acting insulin analogue [Lys(B28), Pro(B29)] human insulin, Diabet. Med., 13, 625–629.
Owens, D. R., Matfin, G., and Monnier, L. (2014) Basal insulin analogues in the management of diabetes mellitus: what progress have we made? Diabetes Metab. Res. Rev., 30, 104–119.
Zinman, B. (2013) Newer insulin analogs: advances in basal insulin replacement, Diabetes Obes. Metab., 15 (Suppl. 1), 6–10.
Hallas-Moller, K. (1956) The lente insulins, Diabetes, 5, 7–14.
Heise, T., Nosek, L., Ronn, B. B., Endahl, L., Heinemann, L., Kapitza, C., and Draeger, E. (2004) Lower within-subject variability of insulin detemir in comparison to NPH insulin and insulin glargine in people with type 1 diabetes, Diabetes, 53, 1614–1620.
Peterkova, V. A., Kuraeva, T. L., and Titovich, E. V. (2003) Lantus (insulin glargine): real benefits and perspectives of use in pediatrics, Saharnii Diabet, 3, 26–28.
Klimontov, V. V., and Myakina, N. E. (2014) Insulin glargine: pharmacokinetic and pharmacodynamic bases of clinical effect, Saharnii Diabet, 4, 99–107.
Migdalis, I. N. (2011) Insulin analogs versus human insulin in type 2 diabetes, Diabetes Res. Clin. Pract., 93 (Suppl. 1), 102–104.
Swinnen, S. G., Simon, A. C., Holleman, F., Hoekstra, J. B., and Devries, J. H. (2011) Insulin detemir versus insulin glargine for type 2 diabetes mellitus, Cochrane Database Syst. Rev., 7, 63–83.
Jonassen, I., Havelund, S., Hoeg-Jensen, T., Steensgaard, D. B., Wahlund, P. O., and Ribel, U. (2012) Design of the novel protraction mechanism of insulin degludec, an ultra-long-acting basal insulin, Pharm. Res., 29, 2104–2114.
Dedov, I. I., and Shestakova, M. V. (2014) Insulin degludec–a new analogue of insulin super-long-acting, Saharnii Diabet, 2, 91–104.
Whittingham, J. L., Havelund, S., and Jonassen, I. (1997) Crystal structure of a prolonged-acting insulin with albumin-binding properties, Biochemistry, 36, 2826–2831.
Sorli, C., Warren, M., Oyer, D., Mersebach, H., Johansen, T., and Gough, S. C. (2013) Elderly patients with diabetes experience a lower rate of nocturnal hypoglycaemia with insulin degludec than with insulin glargine: a meta-analysis of phase IIIa trials, Drugs Aging, 30, 1009–1018.
Henry, R. R., Mudaliar, S., Ciaraldi, T. P., Armstrong, D. A., Burke, P., Pettus, J., Garhyan, P., Choi, S. L., Jacober, S. J., Knadler, M. P., Lam, E. C., Prince, M. J., Bose, N., Porksen, N., Sinha, V. P., and Linnebjerg, H. (2014) Basal insulin peglispro demonstrates preferential hepatic versus peripheral action relative to insulin glargine in healthy subjects, Diabetes Care, 37, 2609–2615.
Mathieu, C., Gillard, P., and Benhalima, K. (2017) Insulin analogues in type 1 diabetes mellitus: getting better all the time, Nat. Rev. Endocrinol., 13, 385–399.
Bergenstal, R. M., Rosenstock, J., Bastyr, E. J., Prince, M. J., Qu, Y., and Jacober, S. J. (2014) Lower glucose variability and hypoglycemia measured by continuous glucose monitoring with novel long-acting insulin LY2605541 versus insulin glargine, Diabetes Care, 37, 659–665.
Caparrotta, T. M., and Evans, M. (2014) PEGylated insulin Lispro, (LY2605541)–a new basal insulin analogue, Diabetes Obes. Metab., 16, 388–395.
Ciaraldi, T. P., and Sasaoka, T. (2011) Review on the in vitro interaction of insulin glargine with the insulin/insulin-like growth factor system: potential implications for metabolic and mitogenic activities, Horm. Metab. Res., 43, 1–10.
Monnier, L., Colette, C., and Owens, D. (2013) Basal insulin analogs: from pathophysiology to therapy. What we see, know, and try to comprehend? Diabetes Metab., 39, 468–476.
Kurapkat, G., Siedentop, M., Gattner, H. G., Hagelstein, M., Brandenburg, D., Grotzinger, J., and Wollmer, A. (1999) The solution structure of a superpotent β-chain-shortened single-replacement insulin analogue, Protein Sci., 8, 499–508.
Jiracek, J., Zakova, L., Antolikova, E., Watson, C. J., Turkenburg, J. P., Dodson, G. G., and Brzozowski, A. M. (2010) Implications for the active form of human insulin based on the structural convergence of highly active hormone analogues, Proc. Natl. Acad. Sci. USA, 107, 1966–1970.
Phillips, N. B., Wan, Z. L., Whittaker, L., Hu, S. Q., Huang, K., Hua, Q. X., Whittaker, J., Ismail-Beigi, F., and Weiss, M. A. (2010) Supramolecular protein engineering: design of zincstapled insulin hexamers as a long acting depot, J. Biol. Chem., 285, 11755–11759.
Berenson, D. F., Weiss, A. R., Wan, Z., and Weiss, M. A. (2011) Insulin analogs for the treatment of diabetes mellitus: therapeutic applications of protein engineering, Ann. N. Y. Acad. Sci., 1243, 40–54.
Morishita, H. (2015) Premixed insulin and intermediate-acting insulin, Nihon Rinsho, 73, 453–457.
Arinina, E. E., and Rashid, M. A. (2012) Clinical and economic benefits of using human insulin analogues, Pharmacoeconomics, 5, 41–46.
Dedov, I. I., and Shestakova, M. V. (2014) Insulin degludec/insulin aspart–the first combined preparation of basal and prandial insulin analogues, Saharnii Diabet, 4, 108–119.
Rodionova, T. I., and Orlova, M. M. (2014) Assessment of efficiency of application of various analogues of insulin in treatment of diabetes type 2, Saratov J. Med. Sci. Res., 10, 461–464.
Nilsson, M. R. (2016) Insulin amyloid at injection sites of patients with diabetes, Amyloid, 23, 139–147.
Berhanu, W. M., and Masunov, A. E. (2012) Controlling the aggregation and rate of release in order to improve insulin formulation: molecular dynamics study of full-length insulin amyloid oligomer models, J. Mol. Model., 18, 1129–1142.
Amdursky, N., Gazit, E., and Rosenman, G. (2012) Formation of low-dimensional crystalline nucleus region during insulin amyloidogenesis process, Biochem. Biophys. Res. Commun., 419, 232–237.
Brange, J., Andersen, L., Laursen, E. D., Meyn, G., and Rasmussen, E. (1997) Toward understanding insulin fibrillation, J. Pharm. Sci., 86, 517–525.
Yang, Y., Petkova, A., Huang, K., Xu, B., Hua, Q. X., Ye, I. J., Chu, Y. C., Hu, S. Q., Phillips, N. B., Whittaker, J., Ismail-Beigi, F., Mackin, R. B., Katsoyannis, P. G., Tycko, R., and Weiss, M. A. (2010) An Achilles’ heel in an amyloidogenic protein and its repair: insulin fibrillation and therapeutic design, J. Biol. Chem., 285, 10806–10821.
Li, Y., Gonga, H., Sunb, Y., Yana, J., Chenga, B., Zhanga, X., Huang, J., Yua, M., Guoa, Y., Zhengb, L., and Huanga, K. (2012) Dissecting the role of disulfide bonds on the amyloid formation of insulin, Biochem. Biophys. Res. Commun., 423, 373–378.
Huang, K., Maiti, N. C., Phillips, N. B., Carey, P. R., and Weiss, M. A. (2006) Structure-specific effects of protein topology on crossbeta assembly: studies of insulin fibrillation, Biochemistry, 45, 10278–10293.
Fodera, V., Librizzi, F., Groenning, M., Van de Weert, M., and Leone, M. (2008) Secondary nucleation and accessible surface in insulin amyloid fibril formation, J. Phys. Chem. B, 112, 3853–3858.
Groenning, M., Frokjaer, S., and Vestergaard, B. (2009) Formation mechanism of insulin fibrils and structural aspects of the insulin fibrillation process, Curr. Protein Pept. Sci., 10, 509–528.
Ahmad, A., Uversky, V. N., Hong, D., and Fink, A. L. (2005) Early events in the fibrillation of monomeric insulin, J. Biol. Chem., 280, 42669–42675.
Zhou, C., Qi, W., Lewis, E. N., and Carpenter, J. F. (2016) Characterization of sizes of aggregates of insulin analogs and the conformations of the constituent protein molecules: a concomitant dynamic light scattering and raman spectroscopy study, J. Pharm. Sci., 105, 551–558.
Woods, R. J., Alarcon, J., McVey, E., and Pettis, R. J. (2012) Intrinsic fibrillation of fast-acting insulin analogs, J. Diabetes Sci. Technol., 6, 265–276.
Blundell, T., Dodson G., Hodgkin, D., and Mercola, D. (1972) Insulin: the structure in the crystal and its reflection in chemistry and biology, Adv. Protein Chem., 26, 279–402.
Selivanova, O. M., Suvorina, M. Y., Surin, A. K., Dovidchenko, N. V., and Galzitskaya, O. V. (2017) Insulin and lispro insulin: what is common and different in their behavior? Curr. Protein Pept. Sci., 18, 57–64.
Selivanova, O. M., and Galzitskaya, O. V. (2012) Structural polymorphism and possible pathways of amyloid fibril formation on the example of insulin protein, Biochemistry (Moscow), 77, 1237–1247.
Selivanova, O. M., Suvorina, M. Y., Dovidchenko, N. V., Eliseeva, I. A., Surin, A. K., Finkelstein, A. V., Schmatchenko, V. V., and Galzitskaya, O. V. (2014) How to determine the size of folding nuclei of protofibrils from the concentration dependence of the rate and lag-time of aggregation. II. Experimental application for insulin and Lispro insulin: aggregation morphology, kinetics, and sizes of nuclei, J. Phys. Chem. B, 118, 1198–1206.
Burke, M. J., and Rougvie, M. A. (1972) Cross-β protein structures. I. Insulin fibrils, Biochemistry, 11, 2435–2439.
Bouchard, M., Zurdo, J., Nettleton, E. J., Dobson, C. M., and Robinson, C. V. (2000) Formation of insulin amyloid fibrils followed by FTIR simultaneously with CD and electron microscopy, Protein Sci., 9, 1960–1967.
Jimenez, J. L., Nettleton, E. J., Bouchard, M., Robinson, C. V., Dobson, C. M., and Saibil, H. R. (2002) The protofilament structure of insulin amyloid fibrils, Proc. Natl. Acad. Sci. USA, 99, 9196–9201.
Koltun, W. L., Waugh, D. F., and Bear, R. S. (1954) An X-ray diffraction investigation of selected types of insulin fibrils, J. Am. Chem. Soc., 76, 413–417.
Winocour, P. H., Mitchell, W. S., Gush, R. J., Taylor, L. J., and Baker, R. D. (1988) Altered hand skin blood flow in type 1 (insulin-dependent) diabetes mellitus, Diabet. Med., 5, 861–866.
Author information
Authors and Affiliations
Corresponding author
Additional information
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.
To whom correspondence should be addressed.
Rights and permissions
About this article
Cite this article
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
Received:
Revised:
Published:
Issue Date:
DOI: https://doi.org/10.1134/S0006297918140122