Abstract
Although an association between membrane phospholipid turnover and exocytotic hormone release has long been recognized, a causal relationship has not been firmly established. Recent studies suggest that glucose (and probably other insulin secretagogues) activates phospholipases and thereby releases membrane-bound arachidonic acid (AA). AA is then converted through islet 12-lipoxygenase to mediators or modulators of insulin release (tentatively identified as peroxides and epoxides of arachidonate). These products may be critical links in stimulus-secretion coupling, since blockade of either AA release or lipoxygenation abrogates insulin release induced by glucose and many other (but not all) stimuli. Cogeneration of prostaglandins from AA through the cyclooxygenase pathway may directly or indirectly modulate the formation and/ or effect of lipoxygenase products. A critical role for lipoxygenase products (and possibly metabolites of AA synthesized by other pathways, such as P-450-dependent monooxygenases) may extend to many secretory cells in addition to pancreatic beta cells. The phasic release of AA described in many cells could explain the biphasic pattern of insulin release induced by glucose. Since some phospholipases and lipoxygenases are Ca++ activated, the release of AA in conjunction with its oxygenation appears to be a concerted system generating "third messengers" for hormone release.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 391-402 |
| Number of pages | 12 |
| Journal | The Journal of Allergy and Clinical Immunology |
| Volume | 74 |
| Issue number | 3 PART 2 |
| DOIs | |
| State | Published - Sep 1984 |
| Externally published | Yes |
Bibliographical note
Funding Information:Since the original report by Hokin and Hokin’ that acetylcholine increases [“‘PI-labeling of PI and phosphatidic acid and concomitantly augments enzyme secretion in the pancreas, many studies have described augmented degradation or resynthesis of phospholipids in conjunction with emiocytotic release of hormones or enzymes. It has been proposed that such events may play a critical role in stimulus-secretion coupling and hormone secretion, possibly by promoting calcium gating or release of calcium from intracellular stores (see reviewszm4).I n pancreatic islets, secretagogue-induced insulin release has been associated with increased hydrolysis of phospholipids, especially of PIsm7a nd polyphosphoinositides,’ or Fromt he Divisionso f Clinical Pharmacologayn d Endocrinology, Departmentosf Medicinea ndP harmacologUy,n iversityo f Col-oradoH ealthS cienceCs enter,a ndt he DenverV eteranAs dmin-istrationM edicalC enterD, enverC, olo.;a ndU niversityo f Wash-ington, Seattle.W ash. Supportedb y grants from the National Institutes of Health (AM311 12,A M15312,a nd AM17047),t he VeteranAs dminis-tration, The Kroc Foundationa,n d the Juvenile Diabetes Foun-dation Reprintr equestsD: r. StewarAt . Metz, Division of Clinical Phar-macologyC, 237,U niversityo f ColoradoH ealthS cienceCs enter, 4200E . Ninth Ave., Denver,C O 80262.