Summary
The early phase of insulin secretion to an oral glucose load was blunted in spontaneous diabetic rats. The blunted insulin secretion was associated with markedly impaired glucose tolerance. A single injection of the islet activating protein (IAP), a protein derived from the culture medium of Bordetella pertussis, into the spontaneous diabetic rats normalised glucose tolerance. The increase in insulin response to glucose was an important contributing factor to the improvement of glucose tolerance. This curative effect of the IAP on the diabetic state was of long duration; glucose tolerance remained virtually normal over a period of one month in the diabetic rats. Perfusion of the isolated pancreas of the diabetic rats pretreated with IAP showed an increase in insulin response to glucose and loss of suppression of glucagon secretion by noradrenaline.
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Parfentjev, A.A., Schleyer, A.L.: The influence of histamine on the blood sugar level of normal and sensitized mice. Arch. Biochem. Biophys.20, 341–346 (1949)
Szentivanyi, A., Fishel, A.W., Talmage, A.W.: Adrenaline mediation of histamine and serotonin hyperglycaemia in normal mice and the absence of adrenaline-induced hyperglycaemia in pertussis-sensitized mice. J. Infect. Dis.113, 86–98 (1963)
Dhar, A.L., Sanyal, A.K.: Carbohydrate metabolism and anaphylaxis. J. Pharm. Pharmacol.15, 628 (1963)
Dhar, A.L., West, A.B.: Sensitization procedures and the blood sugar concentration. J. Pharm. Pharmacol.24, 249–250 (1972)
Gulbenkian, A., Schobert, L., Nixon, C., Tabachnick, A.I.A.: Metabolic effects of pertussis sensitization in mice and rats. Endocrinology83, 885–892 (1968)
Tabachnik, A.I.A., Gulbenkian, A.: Adrenergic changes due to pertussis: insulin, glucose and free fatty acids. Eur. J. Pharmacol.7, 186–195 (1969)
Sumi, T., Ui, M.: Potentiation of the adrenergic beta-receptormediated insulin secretion in pertussis-sensitized rats. Endocrinology97, 352–358 (1975)
Katada, T., Ui, M.: Accelerated turnover of blood glucose in pertussis-sensitized rats due to combined actions of endogenous insulin and adrenergic beta-stimulation. Biochem. Biophys. Acta421, 57–69 (1976)
Dhar, A.L., Dhirwani, A.K., Shethe, A.K.: Pertussis vaccine in diabetics requiring high dose insulin. Br. J. Clin. Pract.29, 119–120 (1975)
Ui, M., Mizushima, Y., Kambayashi, Y., Yajima, M.: Extraction and purification of islet activating protein from the culture supernatant fluids of Bordetella pertussis (Jap.). J. Jpn. Diabetic Soc.20, (Suppl.), 22 (1977)
Goto, Y., Kakizaki, M., Masaki, N.: Spontaneous diabetes produced by selective breeding of normal Wistar rats. Proc. Jpn. Acad.51, 80–85 (1975)
Goto, Y., Kakizaki, M., Toyota, T., Masaki, N., Kitahara, A., Yagihashi, S., Kimura, K.: Spontaneous diabetes produced by repeated selective breeding of normal Wistar rats. In: IXth Congress of the International Diabetes Federation. Excerpta Medica Congr. Ser. No.413, 519–526 (1977)
Yajima, M., Hosoda, K., Kanbayashi, Y., Nakamura, T., Nogimori, K., Mizushima, Y., Nakase, Y., Ui, M.: Isletactivating protein (IAP) in Bordetella pertussis that potentiates insulin secretory responses of rats: Purification and characterization. J. Biochem. (Tokyo)83, 295–303 (1978)
Grodsky, A.M., Batts, A.A., Bennett, A.L., Vcella, C., McWilliams, A.B., Smith, A.F.: Effects of carbohydrates on secretion of insulin from isolated rat pancreas. Am. J. Physiol.205, 638–644 (1963)
Toyota, T., Sato, S., Kudo, M., Abe, K., Goto, Y.: Secretory regulation of endocrine pancreas: Cyclic AMP and glucagon secretion. J. Clin. Endocrinol. Metab.41, 81–89 (1975)
Toyota, T., Abe, K., Kudo, M., Goto, Y.: Effects of trypsin on glucose-induced insulin secretion from the perfused rat pancreas. Tohoku J. Exp. Med.118, 381–385 (1976)
Morgan, A.R., Lazarow, A.: Immunoassay of insulin using a two-antibody system. Proc. Soc. Exp. Biol. Med.110, 29–32 (1962)
Morse, A.I.: Bordetella pertussis and beta adrenergic blockage. In: W. Braun, A.M. Lichenstein, A.W. Parker (ed.): Cyclic AMP, Cell Growth and the Immune Response. Berlin, Heidelberg, New York: Springer 263–269 1974
Fishel, A.W., Szentivanyi, A.K., Talmage, A.W.: Sensitization and desensitization of mice to histamine and serotonin by neurohumors. J. Immunol.89, 8–18 (1962)
Fishel, A.W., Szentivanyi, A.: The absence of adrenalineinduced hyperglycaemia in pertussis-sensitized mice and its relation to histamine and serotonin hypersensitivity. J. Allergy Clin. Immunol.34, 439–454 (1963)
Pieroni, A.E., Bundeally, A.E., Amdar, A.O., Levine, L.: Bordetella pertussis as a beta adrenergic blocking agent. Int. Arch. Allergy Appl. Immunol.41, 637–647 (1971)
Morse, A.I., Morse, A.H.: Isolation and properties of the leukocytosis- and lymphocytosis-promoting factor of Bordetella pertussis. J. Exp. Med.143, 1483–1502 (1976)
Dhar, A.L., Sanyal, A.K., West, A.B.: The relationship of the blood sugar level to the severity of anaphylactic shock. Br. J. Pharmacol.31, 351–355 (1967)
Kreutner, W., Gulbenkian, A., Tabachnik, A.I.A.: Effect of epinephrine on hepatic glycogen phosphorylase and synthetase activities in normal and pertussis-sensitized rat. Biochem. Pharmacol.19, 2561–2567 (1970)
Davidson, A.B., Kaplan, A.A.: Increased insulin binding by hepatic plasma membrane from diabetic rats. Normalization by insulin therapy. J. Clin. Invest.59, 22–30 (1977)
Helderman, A.H., Strom, A.B.: Emergence of insulin receptors upon alloimmune T-cells in the rats. J. Clin. Invest.59, 338–344 (1977)
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Toyota, T., Kakizaki, M., Kimura, K. et al. Islet activating protein (IAP) derived from the culture supernatant fluid of Bordetella pertussis: Effect on spontaneous diabetic rats. Diabetologia 14, 319–323 (1978). https://doi.org/10.1007/BF01223023
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DOI: https://doi.org/10.1007/BF01223023