Alterations in glucose homeostasis in a murine model of Chagas disease

Fnu Nagajyothi, Regina Kuliawat, Christine M. Kusminski, Fabiana S. Machado, Mahalia S. Desruisseaux, Dazhi Zhao, Gary J. Schwartz, Huan Huang, Chris Albanese, Michael P. Lisanti, Rajat Singh, Feng Li, Louis M. Weiss, Stephen M. Factor, Jeffrey E. Pessin, Philipp E. Scherer, Herbert B. Tanowitz

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)886-894
Number of pages9
JournalAmerican Journal of Pathology
Volume182
Issue number3
DOIs
StatePublished - Mar 2013

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Chagas Disease
Trypanosoma cruzi
Homeostasis
Insulin
Glucose
Hypoglycemia
Infection
Glucagon
Pyruvic Acid
Islets of Langerhans
Inflammation
Glucose-6-Phosphatase
Adrenergic Agonists
Gluconeogenesis
Liver
Brazil
Arginine
Blood Glucose
Cell Membrane
Morbidity

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Nagajyothi, F., Kuliawat, R., Kusminski, C. M., Machado, F. S., Desruisseaux, M. S., Zhao, D., ... Tanowitz, H. B. (2013). Alterations in glucose homeostasis in a murine model of Chagas disease. American Journal of Pathology, 182(3), 886-894. https://doi.org/10.1016/j.ajpath.2012.11.027

Alterations in glucose homeostasis in a murine model of Chagas disease. / Nagajyothi, Fnu; Kuliawat, Regina; Kusminski, Christine M.; Machado, Fabiana S.; Desruisseaux, Mahalia S.; Zhao, Dazhi; Schwartz, Gary J.; Huang, Huan; Albanese, Chris; Lisanti, Michael P.; Singh, Rajat; Li, Feng; Weiss, Louis M.; Factor, Stephen M.; Pessin, Jeffrey E.; Scherer, Philipp E.; Tanowitz, Herbert B.

In: American Journal of Pathology, Vol. 182, No. 3, 03.2013, p. 886-894.

Research output: Contribution to journalArticle

Nagajyothi, F, Kuliawat, R, Kusminski, CM, Machado, FS, Desruisseaux, MS, Zhao, D, Schwartz, GJ, Huang, H, Albanese, C, Lisanti, MP, Singh, R, Li, F, Weiss, LM, Factor, SM, Pessin, JE, Scherer, PE & Tanowitz, HB 2013, 'Alterations in glucose homeostasis in a murine model of Chagas disease', American Journal of Pathology, vol. 182, no. 3, pp. 886-894. https://doi.org/10.1016/j.ajpath.2012.11.027
Nagajyothi, Fnu ; Kuliawat, Regina ; Kusminski, Christine M. ; Machado, Fabiana S. ; Desruisseaux, Mahalia S. ; Zhao, Dazhi ; Schwartz, Gary J. ; Huang, Huan ; Albanese, Chris ; Lisanti, Michael P. ; Singh, Rajat ; Li, Feng ; Weiss, Louis M. ; Factor, Stephen M. ; Pessin, Jeffrey E. ; Scherer, Philipp E. ; Tanowitz, Herbert B. / Alterations in glucose homeostasis in a murine model of Chagas disease. In: American Journal of Pathology. 2013 ; Vol. 182, No. 3. pp. 886-894.
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