Activation of the hepatic glycine cleavage enzyme system by glucagon and glucagon-related peptides.
The hepatic glycine cleavage system (GCS) is the principal route for the catabolism of glycine in mammals. Flux through the glycine cleavage system in isolated rat hepatocytes is stimulated about 100% at 100 nM glucagon, with half-maximal stimulation at 4.3 +/- 1.3 nM. Preincubation of the hepatocytes with the glucagon antagonist des-His1-[Glu9]glucagon amide at 10 microM resulted in inhibition of the glucagon-stimulated GCS by approximately 40%, while the antagonist des-His1-[Nle9,Ala11,Ala16]glucagon amide at 10 microM inhibited the glucagon-stimulated GCS by 80%. Oxyntomodulin and glicentin, glucagon-related peptides, were found to stimulate GCS. Oxyntomodulin, 1 microM, and glicentin, 100 nM, stimulated GCS by 100 and 60%, respectively. Glucagon-like peptide 1 (7-36) amide and glucagon (19-29) (10(-10)-10(-7) M) were without effect. Des-His1-[Glu9]glucagon amide at 10 microM inhibited the oxyntomodulin and glicentin-stimulated flux through GCS by about 40%. Thus oxyntomodulin and glicentin can activate the GCS in hepatocytes via interaction with the glucagon receptor but with low affinity.
Mabrouk
G M
GM
Department of Biochemistry, Memorial University of Newfoundland, St. John's, Canada.
Brosnan
J T
JT
D000818:Animals; D053771:Glicentin; D005934:Glucagon / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000502:physiology*; D052216:Glucagon-Like Peptide 1; D004763:Glucagon-Like Peptides / Q000502:physiology; D005998:Glycine / Q000378:metabolism*; D066298:In Vitro Techniques; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D053772:Oxyntomodulin; D010446:Peptide Fragments / Q000502:physiology; D010455:Peptides / Q000502:physiology; D011498:Protein Precursors / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018027:Receptors, Glucagon / Q000378:metabolism
D053772:Oxyntomodulin; D010446:Peptide Fragments; D010455:Peptides; D011498:Protein Precursors; D018027:Receptors, Glucagon; D004763:Glucagon-Like Peptides; D053771:Glicentin; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D005998:Glycine