Malarial toxic antigens synergistically enhance insulin signalling

Taylor, Kathryn R.; Carr, Rachel E.; Playfair, John; Saggerson, E D

doi:10.1016/0014-5793(92)81109-y

Cited by 21 publications

(14 citation statements)

References 26 publications

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“…One explanation for the development of hypoglycaemia accompanying a rodent malaria infection is a pronounced hyperinsulinaemia, which has been reported in mice infected with P. yoelii and P. c. chabaudi [130].…”

Section: Is There Any Involvement Of Tnf-a In Hypoglycaemia?mentioning

confidence: 98%

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Rodent malarias: the mouse as a model for understanding immune responses and pathology induced by the erythrocytic stages of the parasite

Li¹,

Seixas²,

Langhorne³

2001

Med Microbiol Immunol

103

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Section: Is There Any Involvement Of Tnf-a In Hypoglycaemia?mentioning

confidence: 98%

“…Lipid products of the parasites may directly stimulate insulin production, thus causing the drop in blood glucose [129,130]. Drugs that inhibit the production of insulin prevent the development of hypoglycaemia in mice infected with P. yoelii YM or P. c. chabaudi parasites [25].…”

Section: Is There Any Involvement Of Tnf-a In Hypoglycaemia?mentioning

confidence: 99%

Rodent malarias: the mouse as a model for understanding immune responses and pathology induced by the erythrocytic stages of the parasite

Li¹,

Seixas²,

Langhorne³

2001

Med Microbiol Immunol

103

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“…This is reminiscent of our earlier demonstration that supernatants synergize with insulin in stimulating lipogenesis in an in vitro assay of glucose uptake into adipocytes [4]. It [9].…”

Section: Discussionmentioning

confidence: 51%

Blood-Stage malaria infection in diabetic mice

Elased¹,

Souza²,

Playfair³

1995

Clinical and Experimental Immunology

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SUMMARYInfection of mice with blood-stage Plasmodium yoelii and P. chabaudi malaria induced hypoglycaemia in normal mice and normalized the hyperglycaemia of mice made moderately diabetic with streptozotocin (STZ). Injection of parasite supernatants induced hypoglycaemia accompanied by hyperinsulinaemia in normal mice, and in STZ-diabetic mice induced a profound drop in blood glucose and restored insulin secretion; however, severely diabetic mice (two injections of STZ) remained hyperglycaemic with no change in insulin levels. We conclude that malaria infection and parasite-derived molecules lower blood glucose concentration, but only in the presence of some residual pancreatic function. Diabetic mice were less anaemic, exerted a significant control of parasitaemia, and showed enhanced phagocytic activity compared with normal mice.Keywords malaria diabetes streptozotocin glucose insulin INTRODUCTION Hypoglycaemia is a serious complication of Plasmodiumfalciparum malaria [1], but the mechanism responsible is not definitely established. We have previously shown, using the murine malaria parasite P. yoelii, that a supernatant of bloodstage parasites cultured overnight induced hypoglycaemia when injected into normal mice, and that this could be prevented by prior immunization with supernatant or with phosphatidyl inositol [2]; we proposed that the 'toxic antigens' responsible were similar to those we had already shown to induce tumour necrosis factor (TNF) [3]. We also found, using rat adipocytes in vitro, that these toxic antigens appeared to synergize with low levels of insulin in stimulating lipogenesis and inhibiting lipolysis rather than acting on their own [4]. We subsequently showed that hypoglycaemia during infection with P. yoelii and P. chabaudi was associated with hyperinsulinaemia, only occurring with parasitaemia above 50% [5]. Therefore we wished to investigate whether hypoglycaemia during infection could be induced in insulin-deficient diabetic mice, and to clarify the involvement of insulin in the toxic antigeninduced hypoglycaemia. Little literature is available on malaria in diabetic patients (to our knowledge there is only one case report [6] of hypoglycaemia in a diabetic patient infected with P. falciparum), but it is possible to induce hyperglycaemia and insulin deficiency in mice by destroying pancreatic 3 cells with the drug streptozotocin (STZ) [7]. In the present study we have infected STZ-treated diabetic mice with malaria parasites, and measured parasitaemia, blood glucose, and the development of

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“…However, in vitro data point to a unique metabolic effect of malaria toxin. These data show that, in rat adipocytes, malaria toxin acts synergistically with insulin to inhibit lipolysis (35).…”

Section: Discussionmentioning

confidence: 81%

FFAs are not involved in regulation of gluconeogenesis and glycogenolysis in adults with uncomplicated P. falciparum malaria

Thien¹,

Weverling²,

Ackermans³

et al. 2004

American Journal of Physiology-Endocrinology and Metabolism

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. FFAs are not involved in regulation of gluconeogenesis and glycogenolysis in adults with uncomplicated P. falciparum malaria. Am J Physiol Endocrinol Metab 287: E609 -E615, 2004. First published May 27, 2004 10.1152/ajpendo.00026.2004.-In normal subjects, elevation of plasma free fatty acid (FFA) levels stimulates gluconeogenesis (GNG) and inhibits glycogenolysis (GLY). In adults with uncomplicated Plasmodium falciparum malaria, GNG is increased and GLY decreased. To test the hypothesis that FFAs are regulators of GNG and GLY in uncomplicated falciparum malaria, we investigated the effect of inhibition of lipolysis by acipimox in 12 patients with uncomplicated falciparum malaria. Six of them were given acipimox, and six served as controls. Also as controls, six matched healthy subjects were studied on two occasions with and without acipimox. After 16 h of fasting, glucose production and GNG were significantly higher in the malaria patients compared with the healthy controls (P ϭ 0.003 and Ͻ0.0001, respectively), whereas GLY was significantly lower (P Ͻ 0.001), together with elevated plasma concentrations of cortisol and glucagon. During the study, glucose production in patients declined over time (P Ͻ 0.0001), without a statistically significant difference between the acipimox-treated and untreated patients. In controls, however, with acipimox the decline was less outspoken compared with nontreated controls (P ϭ 0.005). GNG was unchanged over time in patients as well as in healthy controls, and no influence of acipimox was found. In patients, GLY declined over time (P Ͻ 0.001), without a difference between acipimox-treated and untreated patients. In contrast, in controls treated with acipimox, no change over time was found, which was statistically different from the decline in untreated controls (P ϭ 0.002). In conclusion, in falciparum malaria, FFAs are not involved in regulation of glucose production, nor of GNG or GLY.Plasmodium falciparum; free fatty acids IN NORMAL SUBJECTS, acute elevation of plasma free fatty acid (FFA) levels has been shown to stimulate gluconeogenesis (GNG) (3,5,6), while at the same time glycogenolysis (GLY) is inhibited (2,5,29,34). The net effect of this reciprocal relationship between GNG and GLY (called autoregulation of glucose production) is that endogenous glucose production remains unchanged (2,7,29). In adult patients with uncomplicated Plasmodium falciparum malaria, endogenous glucose production and GNG are increased, whereas GLY is decreased compared with healthy controls after an overnight fast. The increased GNG could be explained by concomitant increased secretion rates of cortisol, glucagon, norepinephrine, and TNF-␣ (12), but the decreased GLY remained unexplained. Studies in diabetic patients have shown that glucose production in patients with type 2 diabetes is characterized by a significant increase in GNG and a significant decrease in GLY, changes comparable to those found by us in uncomplicated falciparum malaria. Boden et al. (2) have shown that manipulation of...

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Malarial toxic antigens synergistically enhance insulin signalling

Cited by 21 publications

References 26 publications

Rodent malarias: the mouse as a model for understanding immune responses and pathology induced by the erythrocytic stages of the parasite

Rodent malarias: the mouse as a model for understanding immune responses and pathology induced by the erythrocytic stages of the parasite

Blood-Stage malaria infection in diabetic mice

FFAs are not involved in regulation of gluconeogenesis and glycogenolysis in adults with uncomplicated P. falciparum malaria

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