Inhomogeneity of liver glycogen synthesis upon refeeding after starvation.

Normal hepatic glycogen levels are in the range 300-400 pmol/g of tissue wet weight [ 11. Starvation for periods longer than 12 h severely depletes the hepatic glycogen store, as it is rapidly mobilized to provide glucose for extrahepatic tissue metabolism [ 11. Typical levels remaining after mild starvation of 24-48 h are reported as being less than 40 pmol/g of tissue wet weight for the rat and other mammals [ l] . Upon refceding after a period of starvation, there is rapid repletion of the hepatic glycogen store and the long-held belief, based upon experiments performed by Hers [2], was that most glucose absorbed from a carbohydrate load is taken up into the liver and directly converted into glycogen. However, a number of recent reports have suggested that hepatic glycogen synthesis does not proceed via this route under physiological conditions; rather it has been shown that the synthesis is via the so-called indirect route, whereby glucose is metabolized to the level of 3-carbon intermediates before glycogen synthesis (see reviews in [3-71). It has long been known that liver glycogen exists over a vast size range (see 18, Y]), and a study from this laboratory [ 101 showed that post-starvation rabbit liver glycogen repletion is a metabolically inhomogeneous process, with material of large size being synthesized preferentially. This study, along with those from other groups [ 1 1, 121, was performed without accurate knowledge of the values of diffusion coefficients of the glycogen fractions and so accurate molecular mass profiles could not be calculated. Diffusion coefficients have since been measured for glycogen fractions from rat liver ( [ 131, see also [ X I ) and accurate molecular mass profiles described. Since accurate molecular mass data are now available for liver glycogen, it was decided t o reinvestigate the