Alterations induced by phenobarbital, a liver tumor promoter, in hepatocyte receptors for insulin and glucagon and glycogen metabolism.
Exposure of rats to phenobarbital (PB), a tumor promoter in the two-stage hepatocarcinogenesis model, in their diet (0.06%) induces alterations in insulin receptors in the hepatocytes. There is a decrease both in the number of receptors and the dissociation constant (Kd) when compared with animals fed control laboratory diet. The number of insulin receptors/cell and the Kd were respectively: 183,000 +/- 19,000 and 15.3 +/- 2.5 nM for controls; 47,000 +/- 5000 and 2.8 +/- 0.3 nM for PB. The glycogen synthesis in response to insulin was found to be unresponsive in the hepatocytes from rats exposed to PB. Glucagon receptors on hepatocytes, however, were unaltered in animals treated with PB or fed a choline-deficient (CD) diet and the glucagon-stimulated glycogenolytic responses were also comparable to the controls. There is, therefore, a selective alteration in the hepatocyte surface membrane receptors. Both PB and CD have been shown to reduce the hepatic cell membrane receptors for epidermal growth factor, indicating that the two different tumor promoters alter peptide receptors with endogenous protein kinase activities. This similar though selective effect of the tumor promoters on cell surface receptors may be of significance in their action in carcinogenesis by having an effect on the alteration of regulation of cell growth and metabolism.
Betschart
J M
JM
University of Pittsburgh, School of Medicine, PA 15261.
Virji
M A
MA
Gupta
C
C
Shinozuka
H
H
D000818:Animals; D002273:Carcinogens; D005934:Glucagon / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008112:Liver Glycogen / Q000378:metabolism*; D008297:Male; D010634:Phenobarbital / Q000494:pharmacology*; D051381:Rats; D011972:Receptor, Insulin / Q000187:drug effects*; D011964:Receptors, Gastrointestinal Hormone / Q000378:metabolism*; D018027:Receptors, Glucagon
D002273:Carcinogens; D007328:Insulin; D008112:Liver Glycogen; D011964:Receptors, Gastrointestinal Hormone; D018027:Receptors, Glucagon; D005934:Glucagon; D011972:Receptor, Insulin; D010634:Phenobarbital