Diabetes, Vol 37, Issue 2 137-141, Copyright © 1988 by American Diabetes Association
Modulation of insulin secretion from beta-cells by phosphoinositide-derived second-messenger molecules
WS Zawalich
Yale University School of Nursing, New Haven, Connecticut 06536.
In isolated islets, the hydrolysis of membrane phosphoinositides (PI)
participates in the transduction of both extracellular and intracellular
signals into an effective insulin secretory response. A wide variety of
potential second-messenger molecules are generated during the phospholipase
C-mediated cleavage of these strategically situated membrane phospholipids.
Several distinct but interrelated issues are addressed in this perspective.
These include 1) methodological approaches utilized to assess PI turnover,
2) the synergistic relationship between PI-derived second messengers and
cAMP, 3) the contribution of changing PI turnover rates to the biphasic
pattern of insulin output induced by 20 mM glucose, and 4) the role played
by PI turnover in the phenomenon of "memory" displayed by islets after
prior stimulation with various agonists. The concept that events unique to
PI turnover contribute to beta-cell activation is well founded. Because of
uncertainty regarding the exact nature of all PI-derived messengers,
however, it is not yet possible to mold the available information into a
comprehensive theory of beta-cell activation. Future studies will have to
address various important unresolved issues.