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Reversal of hypoglycaemia in murine malaria by drugs that inhibit insulin secretion

Published online by Cambridge University Press:  06 April 2009

K. M. Elased  and
J. H. L. Playfair
K. M. Elased
Affiliation:
Department of Immunology, UCL Medical School, Arthur Stanley House, Tottenham Street, London W1P 9PG, UK
J. H. L. Playfair*
Affiliation:
Department of Immunology, UCL Medical School, Arthur Stanley House, Tottenham Street, London W1P 9PG, UK
*
* Corresponding author. Tel: 0171 380 9349. Fax: 0171 380 9357.
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Summary

We have investigated the metabolic disturbances in 2 murine models of blood-stage malaria, Plasmodium chabaudi and Plasmodium yoelii. Blood glucose, plasma insulin and parasitaemia were measured in normal and infected mice before and after treatment with diazoxide, adrenaline, Sandostatin and quinine. Severe hypoglycaemia and marked hypersinsulinaemia developed during both infections. A single injection of diazoxide (25 mg/kg i.p.) or adrenaline (0·03 mg s.c.) lowered insulin concentrations in normal mice, reversed the hypoglycaemia in both infections and significantly reduced the hyperinsulinaemia in P. chabaudi-infected mice (P < 0·0001). Higher doses of Sandostatin (500 μg/kg s.c.) were required to reverse hypoglycaemia. Quinine (25 mg/kg i.p.) significantly increased blood glucose in normal and infected mice (P < 0·001) and no hypoglycaemia was observed in mice with normal blood glucose for more than 3 h. This study shows that the major cause of hypoglycaemia in murine malaria is hyperinsulinaemia rather than high consumption of glucose by host and parasites or chemotherapy with quinine, and that hypoglycaemia can be reversed by correcting the hyperinsulinaemia.

Keywords

malariainsulinhypoglycaemiadiazoxideSandostatinadrenaline
Type
Research Article
Information
Parasitology , Volume 112 , Issue 6 , June 1996 , pp. 515 - 521
Copyright
Copyright © Cambridge University Press 1996

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References

REFERENCES

Bauer, W., Briner, U., Doepfner, W., Haller, R., Huguenin, R., Marbach, P., Petcher, T. J. & Pless, J. (1982). SMS 201–995: a very potent and selective octapeptide analogue of somatostatin with prolonged action. Life Sciences 31, 1133–40.CrossRefGoogle ScholarPubMed
Boyle, P. J., Justice, K., Krentz, A. J., Nagy, R. J. & Schade, D. S. (1993). Octreotide reverses hyperinsulinemia and prevents hypoglycemia induced by sulfonylurea overdoses. Journal of Clinical Endocrinology and Metabolism 76, 752–6.Google ScholarPubMed
Bruining, G. J., Bosschaart, A. N., Aarsen, R. S. R., Lamberts, S. W. J., Sauer, P. J. J. & Del Pozo, E. (1986). Normalization of glucose homeostasis by a long-acting somatostatin analog SMS 201–995 in a newborn with nesidioblastosis. Acta Endocrinologica 113, 334–9.Google Scholar
Clark, I. A., Gray, K. M., Rockett, E. J., Cowden, W. B., Rockett, K. A., Ferrante, A. & Aggarwal, B. B. (1992). Increased lymphotoxin in human malaria serum, and the ability of this cytokine to increase plasma interleukin-6 and cause hypoglycaemia in mice: implications for malaria pathology. Transactions of the Royal Society of Tropical Medicine and Hygiene 86, 602–7.CrossRefGoogle Scholar
Couturier, E., Sener, A., Anjaneyulu, K. & Malaisse, W. J. (1982). Inhibition by quinine of insulin release and calcium ionophoresis. Molecular Pharmacology 18, 243–6.Google Scholar
Davis, T. M. E., Brown, A. E. & Smith, C. D. (1993). Metabolic disturbance in Plasmodium coatneyi-infected rhesus monkeys. International Journal for Parasitology 23, 557–63.CrossRefGoogle ScholarPubMed
Davis, T. M. E., Pukrittayakamee, S., Supanaranond, W., Looareesuman, S., Krishna, S., Nagachinta, B., Turner, R. C. & White, N. J. (1990). Glucose metabolism in quinine-treated patients with uncomplicated falciparum malaria. Clinical Endocrinology 33, 739–49.CrossRefGoogle ScholarPubMed
Debuyser, A., Drews, G. & Henquin, J. C. (1991). Adrenaline inhibition of insulin release: role of the repolarization of the β cell membrane. Pflügers Archiv 419, 131–7.CrossRefGoogle Scholar
Elased, K., de Souza, J. B. & Playfair, J. H. L. (1995). Blood-stage malaria infection in diabetic mice. Clinicai and Experimental Immunology 99, 440–4.CrossRefGoogle ScholarPubMed
Elased, K. & Playfair, J. H. L. (1994). Hypoglycemia and hyperinsulinemia in rodent models of severe malaria infection. Infection and Immunity 62, 5157–60.CrossRefGoogle ScholarPubMed
Findlay, I., Dunne, M. J., Ullrich, S., Wollheim, C. B. & Petersen, O. H. (1985). Quinine inhibits Ca2+-independent K+ channels whereas tetraethyl-ammonium inhibits Ca2+-activated K+ channels in insulin secreting cells. FEBS Letters 185, 4–8.CrossRefGoogle Scholar
Hales, C. & Randle, P. J. (1963). Immunoassay of insulin with insulin antibody precipitate. The Biochemical Journal 88, 137–46.CrossRefGoogle ScholarPubMed
Henquin, J. C., Horemans, B., Nenquin, M., Verniers, J. & Lambert, A. E. (1975). Quinine-induced modifications of insulin release and glucose metabolism by isolated pancreatic islets. FEBS Letters 57, 280–4.CrossRefGoogle ScholarPubMed
Holloway, P. A. H., Krishna, S. & White, N. J. (1991). Plasmodium berghei: lactic acidosis and hypoglycaemia in a rodent model of severe malaria; effects of glucose, quinine, and dichloroacetate. Experimental Parasitology 72, 123–33.CrossRefGoogle Scholar
Hotamisligil, C. S., Murray, D. L., Choy, L. N. & Spiegelman, B. M. (1994). Tumor necrosis factor α inhibits signalling from the insulin receptor. Proceedings of the National Academy of Sciences, USA 91, 4854–8.CrossRefGoogle ScholarPubMed
Kawo, N. G., Msengi, A. E., Swai, A. B. M., Orskov, H., Alberti, K. G. M. M. & McLarty, D. G. (1991). The metabolic effects of quinine in children with severe and complicated Plasmodium falciparum Malaria in Dar es Salaam. Transactions of the Royal Society of Tropical Medicine and Hygiene 85, 711–13.CrossRefGoogle ScholarPubMed
Looareesuwan, S., Phillips, R. E., White, N. J., Kietinun, S., Karbwang, J., Rackow, C., Turner, R. C. & Warrell, D. A. (1985). Quinine and severe falciparum malaria in late pregnancy. Lancet ii, 4–8.CrossRefGoogle Scholar
Nakaki, T., Nakadate, T. & Kato, R. (1980). α2-Adrenoceptors modulating insulin release from isolated pancreatic islets. Naunyn-Schmiedeberg's Archives of Pharmacology 313, 151–3.CrossRefGoogle Scholar
Okitolonda, W., Pottier, A. & Henquin, J. C. (1986). Glucose homeostasis in rats treated acutely and chronically with quinine. European Journal of Pharmacology 132, 179–85.CrossRefGoogle ScholarPubMed
Patrick, I. T. (1968). Cerebral malaria. British Medical Journal 3, 805 (Letter).CrossRefGoogle ScholarPubMed
Phillips, R. E., Looareesuwan, S., Molyneux, M. E., Hatz, C. & Warrell, D. A. (1993). Hypoglycaemia and counterregulatory hormone responses in severe falciparum malaria: treatment with Sandostatin. Quarterly Journal of Medicine 86, 233–40.Google ScholarPubMed
Potter, D. E., Barnett, J. W. & Woodson, L. C. (1978). Catecholamine-induced changes in plasma glucose, glucagon and insulin in rabbit; effects of somatostatin. Hormone and Metabolic Research 10, 373–7.CrossRefGoogle ScholarPubMed
Shalev, o., Tsur, A. & Rahav, G. (1992). Falciparum malaria-induced hypoglycaemia in a diabetic patient. Postgraduate Medical Journal 68, 281–2.CrossRefGoogle ScholarPubMed
Sherman, I. W. (1979). Biochemistry of Plasmodium (malarial parasites). Microbiological Reviews 43, 453–95.CrossRefGoogle ScholarPubMed
Stehouwer, C. D. A., Lems, W. F., Fischer, H. R. A., Hackeng, W. H. L. & Naafs, M. A. B. (1989). Aggravation of hypoglycaemia in insulinoma patients by the long-acting somatostatin analogue octreotide (Sandostatin). Acta Endocrinologica 121, 34–40.Google ScholarPubMed
Thorton, P. S., Alter, C. A., Katz, L. E. L., Baker, L. & Stanley, C. A. (1993). Short-and long-term use of octreotide in the treatment of congenital hyperinsulinism. Journal of Pediatrics 123, 637–43.CrossRefGoogle Scholar
White, N. J., Warrell, D. A., Chanthavanich, P., Looareesuwan, S., Warrell, M. J., Krishna, S., Williamson, D. H. & Turner, R. C. (1983). Severe hypoglycemia and hyperinsulinemia in falciparum malaria. New England Journal of Medicine 309, 61–6.CrossRefGoogle ScholarPubMed
World Health Organization (1990). Severe and complicated malaria. Transactions of the Royal Society of Tropical Medicine and Hygiene (Suppl. 2) 84, 1–65.CrossRefGoogle Scholar