THE ENDOPLASMIC RETICULUM I4I 



The initial obsenations were derived from a systematic examination of 

 liver tissue from animals fasted for 24 hrs. and for 5 days and from similar 

 animals after periods of re-feeding varying from i to 6 hr. Electron micro- 

 graphs of the liver cells of these animals reveal a constant and specific 

 association between the smooth ER and glycogen. The development of the 

 svstem is particularlv striking during the period of glycogen synthesis at, 

 e.g., 2 hr. after re-feeding following a fast of 24 hr. (Fig. 4). Pictures of 

 this kind supported the early speculation that the membranes and vesicles 

 might contain factors significant in glycogenesis [39]. When the stores of 

 glycogen have reached a maximum (e.g. 6 hr. after re-feeding), the profiles 

 of vesicles intermingling with the glycogen are relatively far less numerous. 

 Whether this represents an absolute reduction in the extent of the system 

 (a reversal of the absolute increase that occurs with re-feeding) or is simply 

 a result of dilution by the glycogen stores has not been determined. 

 Following a period of fast (e.g. 24 hr.), the vesicular component of the 

 residual glycogen complexes is again relatively prominent (Fig. 5), though 

 not so impressive in absolute terms as shortly after re-feeding. The system 

 in the fasted cells is morphologically distinctive ; many of the vesicles show 

 a low density content and are more closely compacted with the glycogen 

 units. There are, in other words, distinguishing ditferences to be noted 

 between the smooth ER and the fasted and re-fed cells (compare Figs. 4 

 and ^5). The image of the glycogen and associated ER in the cell of the 

 fasted animal is repeated in animals that have been given glucagon or 

 epinephrine. Furthermore, the effects of fasting and of glucagon and 

 epinephrine are repeated as well in the fine structure of rat livers perfused 

 under isolation for periods of 4 to 6 hr. [40]. 



There are, unfortunately, several ways to interpret these observations. 

 The structural association of the smooth ER and the glycogen is a specific 



Fig. 5. This shows parts of two adjacent rat liver cells. In this case, in contrast 

 to that shown in Fig. 4, the specimen was taken at the end of a 24-hr. fast period. 



The cells are depleted of their glycogen (gl) except for residual units in small 

 marginal zones of the cytoplasm, as shown here. Following glucagon injections even 

 these residual units are mobilized and many cells appear devoid of any glycogen. 

 The space between the residual glycogen units is filled by somewhat expanded or 

 bloated vesicles of the smooth ER. These seem to fill the available space and crowd 

 close to the glycogen, possibly for functional purposes. Essentially the glycogen is 

 vesicle-locked. The vesicular profiles vary more in size and shape than those in 

 Fig. 4 and seem to have a content of lower density (possibly because something has 

 dissolved out). A number of these vesicles can be seen in close proximity to and 

 possibly blending with the cell surface or membrane (arrows). 



The cell margins are contiguous and run from (cm) to (cm). It is obviously 

 difficult to follow the plasma membranes along this stretch, perhaps because it is 

 discontinuous. Mitochondria (m) are obvious; rough ER {er) is randomly scattered. 

 The specimen was fixed in OSO4, embedded in Epon, and stained after sectioning. 



