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Hormone Effects on Glycogenolysis, Gluconeogenesis, and Cyclic AMP Production by Liver Cells from Rats Fed Diets High in Glucose or Lard¹

Department of Pharmacology, State University of New York, Upstate Medical Center, Syracuse, New York 13210

We have previously described the decreased insulin binding capacity of purified liver plasma membranes from rats fed a carbohydrate free, high lard diet (L) compared to that of plasma membranes from the livers of rats fed a fat free high glucose diet (G). To test the effects of these diets on the capacity of the liver to respond to insulin and to glucagon, groups of rats were fed each diet for 5 to 7 days and their isolated liver cells were studied. Basal rates of glycogenolysis were not significantly different in free liver cells prepared from the two groups, but glycogen content and the increase in glycogenolysis in response to glucagon were greater in the cells from rats fed G diet (G cells). Basal rates of gluconeogenesis from 2 mM lactate were higher in cells from rats fed L diet (L cells) than in G cells whereas both stimulation by glucagon (10^-5 M) and inhibition by insulin (4 mU/ml) were decreased in L compared to G cells. Stimulation of gluconeogenesis by cyclic AMP (10^-4 M) was also less in L cells. There was no significant difference between L and G cells in the basal level of cyclic AMP or in its increase in response to low (1.5 x 10^-9 M) or higher (75 x 10^-9 M) concentrations of glucagon. These were interpreted as evidence that adaptation to changes in diet composition involves coordinate modifications of plasma membrane functions and intracellular processes.

KEY WORDS: • glucagon • insulin • glycogen

¹ This study was supported in part by the National Institutes of Health Grant AM-05410 and by U.S. Public Health Service Grant RR 05402.

Manuscript received 24 April 1978.