Liver glycogen depletion

As noted previously, like skeletal muscle, glycogen depletion in liver during endurance exercise is much less in trained animals and in animals who have had free fatty acids artificially elevated. No evidence exists that the mechanism proposed by Randle to account for the inhibition of carbohydrate metabolism in muscle by oxidation of fatty acids is operative in the liver. Thus other factors must be responsible for the slower rate of liver glycogen depletion in these situations. Such factors may include a smaller increase in catecholamine levels, a smaller reduction in insulin levels, and a smaller reduction in blood flow to the liver during exercise (19,20). 

The preparation for this protocol required a liver glycogen depletion period of 24 hours prior to initial insulin administration. This was done to initiate the gluconeogenic pathway prior to protocol onset thus preventing any loss of lean tissue growth potential. 

The effects of ROM on liver have already been discussed. The potential involvement of ROM in I/R injury is suggested by the finding that glycogen-depleted livers are more susceptible to ischaemic injury. This is thought to be related to accumulation of hypoxanthine during anaerobic metabolism, which serves as a substrate for XO and hence enhanced production of RDM (Younes and Strubelt, 1988). 

After 48 h, marked increase in blood glucose, depressed plasma insulin level, marked depletion of liver glycogen, significant increase in plasma creatinine phosphokinase and glutamic oxaloacetic transaminase activity (Giri etal. 1979)... 

BaP alone produced glycogen depletion in liver cadmium alone caused hepatic perivascular fibrosis. Mixture produced complete disorganization of the hepatic parenchyma, including nuclear degeneration higher increase in EROD activity (by 19-fold), BaP hydroxylase activity (by 71-fold), and cytochrome P-450 microsomal content by 2-fold... 

A well-established inhibitor of gluconeogenesis is ethyl alcohol. This can cause problems in at least two situations. When alcoholic patients enter an alcoholic binge , they do not eat, so that liver glycogen is soon depleted. Since gluconeogenesis is inhibited, both hypoglycaemia and, as indicated below, lactic acidosis can develop. Indeed they may be the two most important factors that precipitate coma and collapse in the alcoholic patient. 

Figure 16.8 Pattern of fuel mobitisatton and utUisatton during early starvation. This is starvation over a period of about 24 hours liver glycogen stores are nearly depleted and fatty acid mobilisation is taking place.

This phase is entered with the depletion of liver glycogen stores and is characterised by two important metabolic features ... 

Rat (albino) 9 mo (F) Hepatic 50 (increased liver weight, morphological changes in bile ducts, lipid filled lysosomes, glycogen depletion, induction of peroxisomal enzymes and cytochrome P-450 system) Mitchell et al. 1985b... 

Dieldrin CNS effects (tremors convulsions, coma), nausea, vomiting Carcinogen (animal positive), liver damage (glycogen depletion, fatty infiltration, necrosis), kidney damage (fatty changes, necrosis)... 

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