Reversal of Hypoglycaemia in Murine Malaria by Drugs that Inhibit Insulin Secretion

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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 hyperinsulinaemia developed during both infections. A single injection of diazoxide (25 mg/kg i.p.) or adrenaline (0.03 mg s.c.) lowered insulinconcentrations 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 micrograms/kg s.c.) were required to reverse hypoglycaemia. Quinine (25 mg/kg i.p.) significantly increased blood glucose in normal and infected mice (P < 0.0010 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.

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