Related Experiment Video
Updated: Jul 28, 2026
09:25
Implementation of a Permeable Membrane Insert-based Infection System to Study the Effects of Secreted Bacterial Toxins on Mammalian Host Cells
Published on: August 19, 2016
Endotoxin lethality is intensified by inhibited gluconeogenesis
Circulatory Shock
|January 1, 1986
Summary
Inhibiting liver glucose synthesis with L-tryptophan significantly worsened endotoxemia in rats, causing hypoglycemia and death. This highlights the critical role of gluconeogenesis in sepsis survival.
Area of Science:
- Biochemistry
- Pathophysiology
- Sepsis Research
Background:
- Endotoxemia and severe gram-negative sepsis have two main lethal factors: metabolic dysfunction (hypoglycemia) and circulatory failure.
- The relative importance of these factors requires direct testing.
Purpose of the Study:
- To investigate the impact of inhibited gluconeogenesis on endotoxin lethality in rats.
- To determine if blocking liver glucose synthesis exacerbates endotoxemia.
Main Methods:
- Rats received intravenous Escherichia coli endotoxin (LD10) with or without intraperitoneal L-tryptophan.
- L-tryptophan was used to inhibit liver gluconeogenesis by forming quinolinic acid.
- Liver intermediates (phosphoenolpyruvate, lactate) were assayed in freeze-clamped samples.
Main Results:
- Simultaneous administration of endotoxin and L-tryptophan led to hypoglycemic convulsions and high mortality (22/24 rats), with 75% dying within 6 hours.
- Endotoxin plus tryptophan significantly reduced liver phosphoenolpyruvate levels (P=0.005) and increased liver lactate 2.8-fold, indicating impaired gluconeogenesis.
- L-tryptophan alone was not lethal.
Conclusions:
- Inhibited gluconeogenesis significantly intensifies the hepatic metabolic derangement associated with endotoxemia.
- Maintaining glucose synthesis is crucial for mitigating endotoxin lethality.
Related Concept Videos
01:24Glucagon-like Receptor Agonists
Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by the...
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by the...
01:23Stringent Response in E. coli
Bacterial growth is closely tied to nutrient availability, with cells proliferating exponentially under favorable conditions and entering a stationary phase when resources become scarce. This transition is mediated by a regulatory mechanism known as the stringent response, which allows bacteria to adapt to nutrient deprivation by modulating gene expression and metabolic activity.During nutrient scarcity, intracellular amino acid levels decline. It results in the accumulation of uncharged tRNAs...
01:12Bacterial Toxins
Bacterial toxins are sophisticated virulence factors that enable pathogenic bacteria to interact with, invade, and damage host tissues. These toxins fall broadly into two types: protein exotoxins, which are secreted into the environment and target specific host receptors, and lipopolysaccharide endotoxins, which are structural components of the bacterial outer membrane released primarily during bacterial lysis or membrane shedding. Exotoxins generally act more selectively, binding to cell...
01:22Botulism
Botulism is a life-threatening neuroparalytic condition caused by botulinum neurotoxin, which is produced by the bacterium Clostridium botulinum, a Gram-positive, spore-forming, obligate anaerobe.In adults, the toxin enters the body in different ways: in foodborne botulism, the preformed toxin is absorbed in the intestine. In wound botulism, spores grow in injured tissue and release the toxin into the blood. Infant botulism differs mechanistically from adult forms. In infants, botulism commonly...
01:28Diphtheria
Diphtheria is an acute, toxin-mediated infectious disease that primarily affects the upper respiratory tract. It is caused by Corynebacterium diphtheriae, a Gram-positive, pleomorphic rod that lacks spore-forming capability and exhibits a characteristic club-shaped morphology under microscopic examination. While C. diphtheriae can asymptomatically colonize mucosal surfaces, clinical disease manifests only when the bacterial strain is lysogenized by a specific β-corynephage. This phage...
01:21Acute Pancreatitis II: Pathophysiology
The pathophysiology of acute pancreatitis centers on injury to pancreatic acinar cells, which initiates a cascade of harmful intracellular events.This injury leads to premature activation of trypsinogen to trypsin in the pancreas. Trypsin then activates other digestive enzymes, such as chymotrypsin, elastase, and phospholipase A2, which begin breaking down pancreatic tissue. The resulting autodigestion causes local inflammation, tissue swelling, hemorrhage, and fat necrosis.Injured acinar cells...