Alterations in glucose homeostasis in a murine model of Chagas disease.

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.

• Authors: 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
• Journal: The American journal of pathology (Am J Pathol) Vol. 182 Issue 3 Pg. 886-94 (Mar 2013) ISSN: 1525-2191 [Electronic] United States
• PMID: 23321322 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Chemical References

• Blood Glucose
• Insulin
• Glucagon
• Glucose

Topics

• Adipose Tissue, White (pathology)
• Animals
• Blood Glucose (metabolism)
• Chagas Disease (blood, metabolism, parasitology, pathology)
• Disease Models, Animal
• Fluorescent Antibody Technique
• Glucagon (blood)
• Gluconeogenesis
• Glucose (metabolism)
• Homeostasis
• Insulin (blood)
• Liver (metabolism, parasitology, pathology)
• Male
• Mice
• Pancreas (parasitology, pathology, ultrastructure)
• Trypanosoma cruzi (physiology)