Genetic obesity and dietary sucrose decrease hepatic glucagon and insulin receptors in LA/N-corpulent rats.
A catabolic and hypolipemic effect of glucagon has been described in normal animals. We therefore studied the role of glucagon in genetically obese, hyperlipemic rats. Twelve genetically obese hyperlipemic LA/N-cp/cp (corpulent) rats and 12 lean littermates were fed either 54% starch or 54% sucrose for 12 weeks. Plasma glucagon and insulin levels and glucagon and insulin binding to liver membranes were measured. Comparing all corpulent and lean animals regardless of diet, a significant (P less than 0.0001) phenotypical effect (cp/cp greater than lean) was observed in plasma insulin levels (464 +/- 54 vs 70.3 +/- 7.6 muu/ml, mean +/- SEM). Insulin binding (2.68 vs 16.1%/50 micrograms protein) and glucagon binding (25.6 vs 47.3%/50 micrograms protein) were both significantly lower (P less than 0.0001) in corpulent rats as compared to their lean littermates. Sucrose feeding had marginal effect on plasma insulin or insulin binding. It, however, decreased glucagon binding in corpulent rats but not in their controls. A significant negative correlation was observed between plasma insulin and insulin binding, while a positive correlation was seen for plasma glucagon and glucagon binding. A significant negative correlation was observed between plasma glucagon and lipogenic enzymes (glucose-6-phosphate dehydrogenase and malic enzyme) in liver and between glucagon binding and these enzymes. We propose that in these genetically obese rats, in addition to hyperinsulinemia, impaired glucagon activity as manifested by decreased glucagon binding to target cells may be an important contributor to the hyperlipemia and obesity. A further decrease in glucagon binding in rats fed sucrose indicates that sucrose, per se, may be an additional contributory factor.
D000818:Animals; D001835:Body Weight; D004040:Dietary Carbohydrates / Q000494:pharmacology*; D005934:Glucagon / Q000097:blood; D005954:Glucosephosphate Dehydrogenase / Q000032:analysis; D007328:Insulin / Q000097:blood; D008099:Liver / Q000032:analysis*; D009765:Obesity / Q000378:metabolism*; D009929:Organ Size; D051381:Rats; D011919:Rats, Inbred Strains; D011972:Receptor, Insulin / Q000032:analysis*; D011956:Receptors, Cell Surface / Q000032:analysis*; D018027:Receptors, Glucagon; D013395:Sucrose / Q000494:pharmacology*
D004040:Dietary Carbohydrates; D007328:Insulin; D011956:Receptors, Cell Surface; D018027:Receptors, Glucagon; D013395:Sucrose; D005934:Glucagon; D005954:Glucosephosphate Dehydrogenase; D011972:Receptor, Insulin