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Gluconeogenesis from Nucleosides in perfused rat livers
Hormone and Metabolic Research = Hormon- Und Stoffwechselforschung = Hormones Et Metabolisme
|September 1, 1981
Summary
Nucleosides like inosine stimulate glucose release from rat livers, with effects varying by rat strain and feeding status. Inosine promotes gluconeogenesis, especially in fasted rats.
Area of Science:
- Biochemistry
- Metabolism
- Physiology
Background:
- Nucleosides and their monophosphates are known to influence cellular metabolism.
- The liver plays a central role in glucose homeostasis.
- Previous studies suggested potential roles for nucleosides in glucose regulation.
Purpose of the Study:
- To investigate the effect of various nucleosides and their monophosphates on hepatic glucose release.
- To characterize the strain-dependent and fasting-dependent effects of inosine on glucose metabolism.
- To elucidate the mechanisms underlying inosine-induced glucose release, including gluconeogenesis and glycogenolysis.
Main Methods:
- Perfusion of isolated rat livers from fed and fasted rats of different strains (Wistar WU, Hannover Wistar, Sprague Dawley).
- Administration of nucleosides and monophosphates to perfused livers.
- Measurement of glucose output and assessment of substrate contribution (gluconeogenesis, glycogenolysis).
- Monitoring of hepatic blood flow to rule out hypoxia-mediated effects.
Main Results:
- Various nucleosides and monophosphates induced significant glucose release from perfused livers in fed rats.
- Inosine's effect on glucose release was strain-dependent, being less pronounced in Wistar WU rats compared to Hannover Wistar and Sprague Dawley rats.
- In 48-hour fasted rats, inosine-induced glucose release was reduced, and strain differences diminished.
- Inosine promoted gluconeogenesis in fasted rats, likely via its ribose moiety.
- In fed Hannover Wistar rats, 60% of inosine-induced hepatic glucose output originated from glycogenolysis.
- Reduced hepatic blood flow observed with nucleoside addition did not explain the glucose-releasing effect.
Conclusions:
- Nucleosides, particularly inosine, are potent stimulators of hepatic glucose release in rats.
- The metabolic response to inosine is influenced by the animal's nutritional status (fed vs. fasted) and genetic strain.
- Inosine contributes to glucose production through both gluconeogenesis (especially in fasted states) and glycogenolysis (in fed states).
- The glucose-releasing effect of nucleosides is not attributable to hypoxia-induced glycogenolysis due to reduced hepatic blood flow.