Back to Search
Start Over
Alterations in glucose homeostasis in a murine model of Chagas disease.
- Source :
-
The American journal of pathology [Am J Pathol] 2013 Mar; Vol. 182 (3), pp. 886-94. Date of Electronic Publication: 2013 Jan 12. - Publication Year :
- 2013
-
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.<br /> (Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Adipose Tissue, White pathology
Animals
Blood Glucose metabolism
Chagas Disease blood
Chagas Disease parasitology
Chagas Disease pathology
Disease Models, Animal
Fluorescent Antibody Technique
Glucagon blood
Gluconeogenesis
Insulin blood
Liver metabolism
Liver parasitology
Liver pathology
Male
Mice
Pancreas parasitology
Pancreas pathology
Pancreas ultrastructure
Trypanosoma cruzi physiology
Chagas Disease metabolism
Glucose metabolism
Homeostasis
Subjects
Details
- Language :
- English
- ISSN :
- 1525-2191
- Volume :
- 182
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- The American journal of pathology
- Publication Type :
- Academic Journal
- Accession number :
- 23321322
- Full Text :
- https://doi.org/10.1016/j.ajpath.2012.11.027