Mechanisms of Insulin Action 
these binding proteins and to determine the na- 
ture of the insulin-stimulated modification. 
Another group of studies involves the rapid 
insulin-stimulated translation of messenger RNA, 
using the enzyme ornithine decarboxylase in a 
rnodel system. Within the past year, we have de- 
termined that insulin can rapidly stimulate the 
translation of certain types of mRNA that contain 
extremely extensive and convoluted secondary 
structures at their 5'-untranslated ends. We have 
proposed that insulin does this by means of a spe- 
cific ability to activate translation initiation fac- 
tors that can unwind or "melt" the RNA second- 
ary structure, and have determined that insulin 
can rapidly stimulate the phosphorylation and 
presumably the activation of these initiation fac- 
tors in intact cells. 
Current studies are focusing on the protein ki- 
nases and phosphatases involved in this initiation 
factor phosphorylation, as well as on other rap- 
idly stimulated, insulin-activated protein kinases 
that could play a role in the phosphorylation of 
the transcription factors alluded to above. In all 
of these cases, the ultimate goal is the elucidation 
of the biochemical steps between insulin binding 
to its receptor and its ultimate intracellular ef- 
fect, such as gene transcription, with the hope 
that steps in this pathway that are abnormal in 
states of insulin resistance can be identified, lead- 
ing to the development of specific therapies. 
44 
