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Effects of endotoxin on carbohydrate metabolism in inbred mice
Abstract:
Effects of endotoxin on carbohydrate metabolism were studied in A/HeJ (endotoxin-sensitive) and C3H/HeJ (endotoxin-resistant) inbred mice. A/HeJ mice developed hypoglycemia within two hours after endotoxin injection, yet liver glycogen content did not differ from controls. Similarly treated C3H/HeJ mice did not develop significant hypoglycemia. Administration of glucagon to endotoxin-treated A/HeJ mice failed to elevate their blood glucose concentrations, while endotoxin-treated mice of the same strain did respond to dibutyryl cyclic AMP with a significant elevation of blood glucose. C3H/HeJ mice on the other hand responded to glucagon and dibutyryl cyclic AMP with elevated blood glucose. Endotoxin-treated C3H/HeJ but not A/HeJ mice were able to carry out gluconeogenesis induced by prednisolone, while both inbred strains showed active glycogenesis after administration of an exogenous glucose load. Administration of glucagon resulted in diminished liver glycogen concentrations in A/HeJ endotoxin-treated mice suggesting no impairment of glycogenolysis. The inability of endotoxin-treated A/HeJ mice to respond to glucagon could be due to impairment of gluconeogenesis. Although endotoxin interfered with the capacity of both inbred strains to respond to glucagon administration with elevation of liver cyclic AMP, the effect was significantly more severe in A/HeJ mice. The susceptibility of A/HeJ mice to the lethal effect of endotoxin may be related to the apparent sensitivity of carbohydrate metabolic pathways to disturbance by endotoxin.
Insights
Endotoxin causes hypoglycemia in sensitive mice by disrupting carbohydrate metabolism and impairing gluconeogenesis. This metabolic dysfunction, particularly the reduced cyclic AMP response, may explain endotoxin
Area of Science:
- Biochemistry
- Immunology
- Physiology
Background:
- Endotoxin (lipopolysaccharide) is a potent immune stimulant.
- Carbohydrate metabolism is crucial for energy homeostasis.
- Understanding endotoxin's metabolic effects is vital for sepsis research.
Purpose of the Study:
- To investigate the impact of endotoxin on carbohydrate metabolism in endotoxin-sensitive (A/HeJ) and endotoxin-resistant (C3H/HeJ) mice.
- To elucidate the mechanisms underlying endotoxin-induced hypoglycemia.
Main Methods:
- Comparative study of endotoxin-treated and control mice.
- Measurement of blood glucose and liver glycogen levels.
- Assessment of responses to glucagon, dibutyryl cyclic AMP, and prednisolone.
Main Results:
- A/HeJ mice developed hypoglycemia post-endotoxin, unlike C3H/HeJ mice.
- Endotoxin-impaired gluconeogenesis and glucagon response in A/HeJ mice.
- Both strains showed normal glycogenesis, but A/HeJ mice had a more severe reduction in cyclic AMP response to glucagon.
Conclusions:
- Endotoxin significantly disrupts carbohydrate metabolism, particularly gluconeogenesis and the cyclic AMP pathway, in sensitive mice.
- Impaired metabolic pathways, especially in A/HeJ mice, may contribute to endotoxin's lethal effects.
- These findings highlight the critical role of metabolic regulation in endotoxin tolerance.