Login | Register

Polymyxin B is an inhibitor of insulin-induced hypoglycemia in the whole animal model. Studies on the mode of inhibitory action

Title:

Polymyxin B is an inhibitor of insulin-induced hypoglycemia in the whole animal model. Studies on the mode of inhibitory action

Amir, Shimon ORCID: https://orcid.org/0000-0003-1919-5023, Sasson, Shlomo, Kaiser, Nurit, Meyerovitch, Joseph and Shechter, Yoram (1987) Polymyxin B is an inhibitor of insulin-induced hypoglycemia in the whole animal model. Studies on the mode of inhibitory action. The Journal of Biological Chemistry, 262 (14). pp. 6663-6667.

[img]
Preview
Text (application/pdf)
Amir-JBiolChem-1987.pdf - Published Version
Available under License Spectrum Terms of Access.
578kB

Official URL: http://www.jbc.org/content/262/14/6663.long

Abstract

The cyclic decapeptide, polymyxin B (PMXB), was found to inhibit hypoglycemia in mice receiving exogenous insulin (Amir, S., and Shechter, Y. (1985) Eur. J. Pharmacol. 110, 283-285). In this study, we have extended this observation to rats. Insulin-dependent hypoglycemia in rats is efficiently blocked at a 12:1 molar ratio of PMXB to insulin. This effect is highly specific, as it could not be mimicked by a variety of antibiotics or positively charged substances. Chemical modifications of PMXB have revealed that the ring structure, rather than the tail structure, is important for anti-insulin-like activity. Colistin A, which differs from PMXB by one conservative amino acid substitution in the ring structure, is devoid of this activity. Polymyxin B does not interact with insulin, nor does it alter the rate of insulin absorption and/or degradation, or the ability of insulin to bind to target tissues. This peptide inhibits hypoglycemia by blocking insulin-dependent activation of the hexose transport mechanism, as deduced by in vitro studies. The effect of insulin in stimulating hexose uptake (and subsequent glucose metabolism) in both isolated muscle tissue and adipocytes is blocked with little or no effect on the basal activities of these processes. Colistin A has no significant inhibiting effect. Other insulin-dependent activities, such as inhibition of lipolysis in adipocytes or synthesis of DNA in muscle cells, are not inhibited. It is concluded that PMXB inhibits, in a highly specific manner, the action of insulin in stimulating hexose transport and subsequent glucose metabolism, both in vitro and in the whole animal model.

Divisions:Concordia University > Faculty of Arts and Science > Psychology
Item Type:Article
Refereed:Yes
Authors:Amir, Shimon and Sasson, Shlomo and Kaiser, Nurit and Meyerovitch, Joseph and Shechter, Yoram
Journal or Publication:The Journal of Biological Chemistry
Date:15 May 1987
ID Code:983740
Deposited By: DANIELLE DENNIE
Deposited On:13 Apr 2018 14:41
Last Modified:13 Apr 2018 14:41

References:

Jacobs, S., and Cuatrecasas, P. (1981) Endocr. Rev. 2, 251-263

Shechter, Y. (1985) in The Receptors (Conn, M. P., ed) Vol. 2, pp. 221-224, Academic Press, Orlando, FL

Czech, M. P. (1985) Annu. Reu. Physiol. 47, 357-381

Czech, M. P. (1977) Annu. Reu. Biochem. 46, 357-381

Czech, M. P. (1980) Diabetes 29, 399-409

Shechter, Y., and Karlish, S. J. D. (1980) Nature 284, 556-558

Degani, H., Gochin, M., Karlish, S. J. D., and Shechter, Y. (1981) Biochemistry 20, 5795-5799

Dubyak, G. R., and Kleinzeller, A. (1980) J. Biol. Chem. 255, 5306-5312

Tamura, S., Brown, T. A., Whipple, J. H., Yamaguchi, Y.-F., Dubler, R. E., Cheng, K., and Larner, J. (1984) J. Biol. Chem. 259, 6650-6658

Chandramouli, U., Milligan, M., and Carter, J. R., Jr. (1977) Biochemistry 16, 1151-1158

Kono, T., Robinson, F. W., Sarver, J. A., Vega, F. V., and Pointer, R. H. (1977) J. Biol. Chem. 252, 2226-2233

Siegel, J., and Olefsky, J. M. (1980) Biochemistry 19, 2183-2190

Shechter, Y. (1984) Proc. Natl. Acad. Sci. U. S. A. 81,327-331

Begum, N., Tepperman, H. M., and Tepperman, J. (1986) Endocrinology 118, 287-292

Amir, S., and Shechter, Y. (1985) Eur. J. Pharmmol. 110, 283-285

Habeeb, A. F. S. A. (1966) Anal. Biochem. 14, 328-336

Hunter, W. M., and Greenwood, F. C. (1962) Nature 194,495-496

Rodbell, M. (1964) J. Biol. Chem. 239,375-380

Moody, A. J., Stan, M. A., Stan, M., and Gliemann, J. (1974) Horm. Metab. Res. 6, 12-16

Olefsky, J. M. (1976) J. Clin. Invest. 57,842-851

Shechter, Y. (1982) Endocrinology 110, 1579-1583

Gliemann, J., Osterland, K., Venter, J., and Gammeltoft, S. (1972) Biochim Biophys. Acta 286, 1-9

Kaiser, N., Tur-Sinai, A,, Hasin, M., and Cherasi, E. (1985) Am. J. Physiol. 249, E292-E298

Vaara, M., and Vaara, T. (1983) Antimicrob. Agents Chemother. 24,107-113

Kunin, C. M. (1970) J. Infect. Dis. 121,55-64

Kunin, C. M., and Bugg, A. (1971) J. Infect. Dis. 124,394-400

Craig, W. A., and Kunin, C. M. (1973) J. Pharmmol. Exp. Ther. 184,757-765
All items in Spectrum are protected by copyright, with all rights reserved. The use of items is governed by Spectrum's terms of access.

Repository Staff Only: item control page

Downloads per month over past year

Research related to the current document (at the CORE website)
- Research related to the current document (at the CORE website)
Back to top Back to top