An Insulin-like Hybrid Consisting of a Modified A-domain of Human Insulin-like Growth Factor I and the B-chain of Insulin

Overview

Journal J Protein Chem

Specialties Biochemistry
Chemistry

Date 1990 Aug 1

PMID 2275749

Authors

L Zong

G T Burke

P G KATSOYANNIS

Affiliations

Soon will be listed here.

Abstract

We have synthesized an insulin-like compound, consisting of the B-chain of bovine insulin and an A-chain corresponding to the A-domain of human insulin-like growth factor-I (IGF-I), in which the isoleucine residue normally present in position 2 of the A-domain of IGF-I has been replaced with glycine. Biological evaluation of the compound indicated that its insulin-like activity (insulin receptor-binding and stimulation of lipogenesis) was 0.2%, and its growth-factor activity (stimulation of thymidine incorporation) was less than 1%, both relative to natural insulin. We conclude that interactions between IleA2 and TyrA19, which are crucial to high biological activity in insulin, are also present in IGF-I, and are equally critical for its biological activity.

References

Gilman A, PHILIPS F, KOELLE E . The renal clearance of thiosulfate with observations on its volume distribution. Am J Physiol. 2010; 146:348-57. DOI: 10.1152/ajplegacy.1946.146.3.348. View

Kitagawa K, Ogawa H, Burke G, CHANLEY J, KATSOYANNIS P . Critical role of the A2 amino acid residue in the biological activity of insulin: [2-glycine-A]- and [2-alanine-A]insulins. Biochemistry. 1984; 23(7):1405-13. DOI: 10.1021/bi00302a011. View

Joshi S, Burke G, KATSOYANNIS P . An insulin-like compound consisting of the B-chain of bovine insulin and an A-chain corresponding to a modified A- and the D-domains of human insulin-like growth factor I. J Protein Chem. 1990; 9(2):235-46. DOI: 10.1007/BF01025314. View

Okada Y, CHANLEY J, Burke G, KATSOYANNIS P . [A2-Norleucine]insulin. An analog with unanticipated biological properties. Hoppe Seylers Z Physiol Chem. 1981; 362(6):629-38. DOI: 10.1515/bchm2.1981.362.1.629. View

Schwartz G, Burke G, KATSOYANNIS P . A superactive insulin: [B10-aspartic acid]insulin(human). Proc Natl Acad Sci U S A. 1987; 84(18):6408-11. PMC: 299085. DOI: 10.1073/pnas.84.18.6408. View

KATSOYANNIS P, Tometsko A, Zalut C, Johnson S, TRAKATELLIS A . Studies on the synthesis of insulin from natural and synthetic A and B chains. I. Splitting of insulin and isolation of the S-sulfonated derivatives of the A and B chains. Biochemistry. 1967; 6(9):2635-42. DOI: 10.1021/bi00861a001. View

Blundell T, Bedarkar S, Rinderknecht E, HUMBEL R . Insulin-like growth factor: a model for tertiary structure accounting for immunoreactivity and receptor binding. Proc Natl Acad Sci U S A. 1978; 75(1):180-4. PMC: 411209. DOI: 10.1073/pnas.75.1.180. View

Horvat A, Li E, KATSOYANNIS P . Cellular binding sites for insulin in rat liver. Biochim Biophys Acta. 1975; 382(4):609-20. DOI: 10.1016/0005-2736(75)90226-6. View

Pullen R, LINDSAY D, Wood S, Tickle I, Blundell T, Wollmer A . Receptor-binding region of insulin. Nature. 1976; 259(5542):369-73. DOI: 10.1038/259369a0. View

10.

Rinderknecht E, HUMBEL R . The amino acid sequence of human insulin-like growth factor I and its structural homology with proinsulin. J Biol Chem. 1978; 253(8):2769-76. View

11.

Zapf J, Schoenle E, FROESCH E . Insulin-like growth factors I and II: some biological actions and receptor binding characteristics of two purified constituents of nonsuppressible insulin-like activity of human serum. Eur J Biochem. 1978; 87(2):285-96. DOI: 10.1111/j.1432-1033.1978.tb12377.x. View

12.

Kitagawa K, Ogawa H, Burke G, CHANLEY J, KATSOYANNIS P . Interaction between the A2 and A19 amino acid residues is of critical importance for high biological activity in insulin: [19-leucine-A]insulin. Biochemistry. 1984; 23(19):4444-8. DOI: 10.1021/bi00314a031. View

13.

Blundell T, Bedarkar S, HUMBEL R . Tertiary structures, receptor binding, and antigenicity of insulinlike growth factors. Fed Proc. 1983; 42(9):2592-7. View

14.

Schwartz G, Burke G, KATSOYANNIS P . A highly potent insulin: des-(B26-B30)-[AspB10,TyrB25-NH2]insulin(human). Proc Natl Acad Sci U S A. 1989; 86(2):458-61. PMC: 286489. DOI: 10.1073/pnas.86.2.458. View

15.

King G, Kahn C . Non-parallel evolution of metabolic and growth-promoting functions of insulin. Nature. 1981; 292(5824):644-6. DOI: 10.1038/292644a0. View

16.

Rodbell M . METABOLISM OF ISOLATED FAT CELLS. I. EFFECTS OF HORMONES ON GLUCOSE METABOLISM AND LIPOLYSIS. J Biol Chem. 1964; 239:375-80. View

17.

Chen Z, Schwartz G, Zong L, Burke G, CHANLEY J, KATSOYANNIS P . Determinants of growth-promoting activity reside in the A-domain of insulin-like growth factor I. Biochemistry. 1988; 27(16):6105-11. DOI: 10.1021/bi00416a041. View