ORAL PROTEIN EFFECTS ON LIVER GLYCOGEN METABOLISM

The long term objective of these studies is to understand how ingestion of a mixed meal composed of protein, fat, and carbohydrate affects glycogen and glucose metabolism in the liver. This study will focus on the effects of protein + carbohydrate (CHO) and protein + fat ingestion. Protein ingestion results in an increase in insulin and glucagon concentrations, two hormones having opposing effects on liver metabolism, but little effect on glucose concentration. It also results in an increase in alanine and lactate concentration in the portal circulation, two of the major gluconeogenic precursors. The net result of pure protein ingestion is hepatic glycogenolysis. On the other hand, glucose administration results in an increase in glucose and insulin, but a decrease in glucagon concentration. It also results in a small increase in alanine but a large increase in lactate in the portal circulation. The net result of pure glucose ingestion is hepatic glycogenesis. Since ingestion of the two nutrients individually has opposite effects of hepatic glycogen metabolism, the net effect of ingestion of these two nutrients simultaneously will be of particular interest. The effect of fat on the system has not been well studied. The specific objectives of this project are 4 fold. The first is to determine the acute effects of protein administered orally with glucose on protein digestion and amino acid absorption. The second is to determine if the addition of protein to a glucose meal affects the accumulation of hepatic glycogen, and if so how. The third is to determine how the addition of protein to a glucose meal affects overall glucose metabolism in the liver. Of particular interest will be how it may affect the flux of lactate and non-lactate substrates through the gluconeogenic pathway. Lastly, quantitation and comparison will be done of the digestion of protein and the absorption of amino acids when protein is given alone, or with glucose. There is indirect evidence that orally administered glucose may affect protein digestion and/or amino acid absorption, or amino acid disposition. Similar studies will be done using test meals of fats + protein. Dietary regiments frequently are advocated for patients with a variety of medical problems. In order to predict the physiologic response to a recommended dietary regimen, it is important to understand metabolism, and the effects of various nutrients on intermediary metabolism. The proposed studies should provide such information. Rats will be used as an animal model. They are omnivores, as are humans. Considerable data has been accumulated in rats regarding the effects of various nutrients on glycogen metabolism. These data can be sued for comparative purposes. Rats will be administered test meals of protein + CHO and protein + fat, given in proportions similar to those present in the normal rat, and human diet. At various periods of time after administration of the test meals, the flux of hormones and metabolites known to affect hepatic glycogen and glucose metabolism will be measured. The concentration of effector metabolites will be measured in the liver as well. These data will be correlated with the activity of key enzymes important in regulating glycogen metabolism in the liver. The proposed studies should be important in elucidating principles for fuel metabolism in rats, which can be used as a guide for humans.