Somatostatin: Mechanism of Action in Pancreatic Islet β-Cells

Abstract

The widespread role of somatostatin (SRIF) as a mediator of function in the brain and gut has stimulated interest in it mechanism of action. We have examined the mode of action of SRIF in stimulus-secretion coupling in the pancreatic islet beta-cell to determine whether SRIF antagonizes the glucose-induced decrease in K+ permeability (PK). The influence of SRIF on 86Rb fluxes and insulin release in cultured rat islet cells, and also the electrical events recorded from cultured islets and microdissected mouse islets, was examined. In cultured islets, 100 ng/ml SRIF in the presence of 16.7 mM glucose inhibited the incidence of spike activity and evoked hyperpolarization. This effect was counteracted by 0.1 mM quinine and 20 mM tetraethylammonium (TEA), drugs that inhibit the Ca2+-sensitive or voltage-sensitive increase in PK, respectively. These agents also counteracted the inhibitory influence of SRIF on glucose-induced insulin release in cultured islets. SRIF disrupted the typical glucose-induced oscillatory pattern of electrical activity (burst activity) during continuous microelectrode recordings in mouse beta-cells, resulting in a transient 5mV hyperpolarization and a decrease in the frequency of generation of burst activity. The presence of 20 mm TEA prevented the influence of SRIF on the electrical activity. SRIF had no effect on the accumulation of 86Rb into islet cells obtained in the presence of 16.7 mM glucose. However, SRIF enhanced the rate of 86Rb efflux from cells exposed to glucose. SRIF-induced enhancement of 86Rb efflux was antagonized by TEA or quinine. These results indicate that SRIF may activate PK as its primary mode of action, an event that may be sufficient to reduce the accumulation of intracellular Ca2+ thereby disrupting glucose-induced stimulus-secretion coupling.

Hyperpolarization of the membrane potential caused by somatostatin in dissociated human pituitary adenoma cells that secrete growth hormone.

“…The membrane-signal transduction mechanism for somatostatin action has not yet been fully clarified in the pituitary. In the rat pancreas islet it has been reported that somatostatin activates a K+ conductance and inhibits glucose-induced insulin release (11). In analogy, a similar mechanism of somatostatin may exist in the pituitary.…”

Effects of α‐adrenoceptor antagonists on clonidine‐induced inhibition of insulin secretion by isolated pancreatic islets

“…glucagon and somatostatin which may modulate 1-cell function (Unger & Orci, 1977;Pace & Tarvin, 1981) (not excluding the possibility of a-adrenoceptors being located on the other cell types). In order to explore this possibility we studied mouse islets, which contain a lower proportion of non-p-cells than rat islets (Dean, 1973;Hoftiezer & Carpenter, 1973), and which were perifused in order to minimize the effects of secretory products on 1-cells.…”

The paradoxical effects of somatostatin on the bioactivity and production of cytotoxins derived from human peripheral blood mononuclear cells

“…The production of TNF and LT are regulated differently (Centuri et al, 1987), and these two cytokines are produced by dissimilar cell types (Goeddel et al, 1986;Paul & Ruddle, 1988), thus it is possible an agent could affect the production of one cytotoxin, but not the other. The mechanism of the inhibition in production of cytokines could possibly relate to the fact SMS may influence membrane permeability to calcium (Pace & Tarvin, 1981) which is important in the secretion of other cytokines (Cesario et al, 1988). Since SMS does affect bioactivity, we had exhaustively dialysed (with five bath changes) supernatants to remove SMS.…”