Release of Newly Synthesized Hormone from the Pancreatic Beta Cell 1

Abstract

Work in the pancreatic beta cell and insulin secretion pioneered by Lacy 1 , 2 and Orci 3 , 4 , 5 , 6 developed the concept of exocytotic release of hormone via secretory granules binding to the cell membrane. This work is well-known and has been adequately reviewed on a number of occasions. However, a number of pulse-labeling studies suggested that newly synthesized insulin (and insulin precursors) was secreted preferentially 7 , 8 , 9 , 10 , 11 , 12 . Although little is known about the mechanism by which this occurs, it appears that islets store a portion of their total insulin in a labile compartment that contains newly synthesized hormone and is preferentially secreted in response to glucose. Recently, Halbane 13 and Gold et al. 14 concurrently demonstrated a number of conditions where newly synthesized hormone (proinsulin and insulin) is preferentially secreted from the beta cell, thereby providing some insight into the mechanism of preferential secretion. In addition, Gold et al. 14 showed that the percentage of radioactive proinsulin in secreted, newly synthesized hormone after 30 and 68 min of stimulation with 20 mM glucose was 71.3 and 62.6%, respectively. This means that a large proportion of the secreted, newly synthesized hormone is actually proinsulin and only about 30-40% is insulin. Interestingly, after 162 min of stimulation with 20 mM glucose the percentage of proinsulin in the secreted hormone decreased to 15.6%, implying that 85% of the secreted hormone was insulin. In light of this data, the cell biologist faces a dilemma of describing a morphological mechanism that accounts for the preferential release of newly synthesized hormone.