Trypanosoma cruzi infection alters glucose metabolism at rest and during exercise without modifying the morphology of pancreatic islets in rats

Novaes, Rômulo Dias; Gonçalves, Reggiani Vilela; Penitente, Arlete Rita; Talvani, André; Neves, Clóvis Andrade; Natali, Antônio José; Maldonado, Izabel R.S.C.

doi:10.1016/j.prp.2012.05.016

Cited by 5 publications

(2 citation statements)

References 38 publications

(62 reference statements)

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“…When β-cells, and islets in general, were identified as infected, qualitative changes were observed (Lenzi et al 1996; Novaes et al 2012). Despite infection, the overall number of β-cells was not reduced (dos Santos et al 1999a).…”

Section: Discussionmentioning

confidence: 99%

“…To understand the molecular basis for reduced functional capacity and exercise tolerance observed in patients with Chagas disease, glucose and insulin utilization was examined in T. cruzi -infected rats (Novaes et al 2012). These experimental parameters were chosen because exercise depends on increased rate of glycolysis and insulin stimulated glucose uptake into contracting skeletal muscles (Goodyear and Kahn 1998).…”

Section: Evidence From Preclinical Studies That T Cruzi Infection Rementioning

confidence: 99%

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Alterations in pancreatic β cell function and Trypanosoma cruzi infection: evidence from human and animal studies

et al. 2016

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The parasite Trypanosoma cruzi causes a persistent infection, Chagas disease, affecting millions of persons in endemic areas of Latin America. As a result of immigration, this disease has now been diagnosed in non-endemic areas worldwide. Although, the heart and gastrointestinal tract are the most studied, the insulin secreting β cell of the endocrine pancreas is also a target of infection. In this review, we summarize available clinical and laboratory evidence to determine whether T. cruzi-infection-mediated changes of β cell function is likely to contribute to the development of hyperglycemia and diabetes. Our literature survey indicates that T. cruzi infection of humans and of experimental animals relates to altered secretory behavior of β cells. The mechanistic basis of these observations appears to be a change in stimulus-secretion pathway function rather than the loss of insulin producing β cells. Whether this attenuated insulin release ultimately contributes to the pathogenesis of diabetes in human Chagas disease however, remains to be determined. Since the etiologies of diabetes are multifactorial including genetic and life-style factors, the use of cell- and animal-based investigations, allowing direct manipulation of these factors, are important tools in testing if reduced insulin secretion has a causal influence on diabetes in the setting of Chagas disease. Long-term clinical investigations will be required to investigate this link in humans.

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Section: Discussionmentioning

confidence: 99%

Section: Evidence From Preclinical Studies That T Cruzi Infection Rementioning

confidence: 99%

Alterations in pancreatic β cell function and Trypanosoma cruzi infection: evidence from human and animal studies

et al. 2016

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Alterations in Glucose Homeostasis in a Murine Model of Chagas Disease

Nagajyothi

Kuliawat

Kusminski

et al. 2013

The American Journal of Pathology

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Chagas disease, caused by Trypanosoma cruzi, is an important cause of morbidity and mortality primarily resulting from cardiac dysfunction, although T. cruzi infection results in inflammation and cell destruction in many organs. We found that T. cruzi (Brazil strain) infection of mice results in pancreatic inflammation and parasitism within pancreatic β-cells with apparent sparing of α cells and leads to the disruption of pancreatic islet architecture, β-cell dysfunction, and surprisingly, hypoglycemia. Blood glucose and insulin levels were reduced in infected mice during acute infection and insulin levels remained low into the chronic phase. In response to the hypoglycemia, glucagon levels 30 days postinfection were elevated, indicating normal α-cell function. Administration of L-arginine and a β-adrenergic receptor agonist (CL316, 243, respectively) resulted in a diminished insulin response during the acute and chronic phases. Insulin granules were docked, but the lack of insulin secretion suggested an inability of granules to fuse at the plasma membrane of pancreatic β-cells. In the liver, there was a concomitant reduced expression of glucose-6-phosphatase mRNA and glucose production from pyruvate (pyruvate tolerance test), demonstrating defective hepatic gluconeogenesis as a cause for the T. cruzi-induced hypoglycemia, despite reduced insulin, but elevated glucagon levels. The data establishes a complex, multi-tissue relationship between T. cruzi infection, Chagas disease, and host glucose homeostasis.

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Trypanosoma cruzi-induced depressive-like behavior is independent of meningoencephalitis but responsive to parasiticide and TNF-targeted therapeutic interventions

Vilar-Pereira

Silva

Pereira

et al. 2012

Brain, Behavior, and Immunity

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Inflammatory cytokines and microbe-borne immunostimulators have emerged as triggers of depressive behavior. Behavioral alterations affect patients chronically infected by the parasite Trypanosoma cruzi. We have previously shown that C3H/He mice present acute phase-restricted meningoencephalitis with persistent central nervous system (CNS) parasitism, whereas C57BL/6 mice are resistant to T. cruzi-induced CNS inflammation. In the present study, we investigated whether depression is a long-term consequence of acute CNS inflammation and a contribution of the parasite strain that infects the host. C3H/He and C57BL/6 mice were infected with the Colombian (type I) and Y (type II) T. cruzi strains. Forced-swim and tail-suspension tests were used to assess depressive-like behavior. Independent of the mouse lineage, the Colombian-infected mice showed significant increases in immobility times during the acute and chronic phases of infection. Therefore, T. cruzi-induced depression is independent of active or prior CNS inflammation. Furthermore, chronic depressive-like behavior was triggered only by the type I Colombian T. cruzi strain. Acute and chronic T. cruzi infection increased indoleamine 2,3-dioxygenase (IDO) expression in the CNS. Treatment with the selective serotonin reuptake inhibitor (SSRI) fluoxetine abrogated the T. cruzi-induced depressive-like behavior. Moreover, treatment with the parasiticide drug benznidazole abrogated depression. Chronic T. cruzi infection of C57BL/6 mice increased tumor necrosis factor (TNF) expression systemically but not in the CNS. Importantly, TNF modulators (anti-TNF and pentoxifylline) reduced immobility. Therefore, direct or indirect parasite-induced immune dysregulation may contribute to chronic depressive disorder in T. cruzi infection, which opens a new therapeutic pathway to be explored.

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Trypanosoma cruzi infection alters glucose metabolism at rest and during exercise without modifying the morphology of pancreatic islets in rats

Cited by 5 publications

References 38 publications

Alterations in pancreatic β cell function and Trypanosoma cruzi infection: evidence from human and animal studies

Alterations in pancreatic β cell function and Trypanosoma cruzi infection: evidence from human and animal studies

Alterations in Glucose Homeostasis in a Murine Model of Chagas Disease

Trypanosoma cruzi-induced depressive-like behavior is independent of meningoencephalitis but responsive to parasiticide and TNF-targeted therapeutic interventions

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