Somatostatin: Regulation of Secretion

Abstract

Somatostatin is released in the blood, in synaptic clefts, and in the intercellular space in response to a variety of stimuli. In view of its multiple functions, various sites of synthesis and release, and rapid inactivation, as well as extremely low levels of somatostatin in the peripheral blood, somatostatin can hardly be considered to be a hormone whose target is reached via the general circulation. The target organs or cells may be located near the somatostatin-producing cells and can be reached via local circulation such as the hypophyseal portal system and the microportal circulation in the gut mucous membrane. Somatostatin released from the neurons acts as a hypophyseotropic hormone and a neurotransmitter or neuromodulator. Furthermore, somatostatin may also act in a paracrine fashion by being released into the intercellular space. This space may sometimes be compartmentalized by tight junctions so that the action of the peptideis limited only to the adjacent cells. In this fashion, the pancreatic islet somatostatin influences nearby A- and B-cell activities. Gut D cells, prototypes of APUD or paraneuron cells, show considerable similarity to neurosecretory cells not only in biochemical processes but also morphologically. While the somatostatin neurons in the brain respond to dopaminergic and catecholaminergic agonists, D cells in the gut respond to chemical stimuli in the lumen by sensing them with microvilli. They release somatostatin into the blood stream, into the intercellular space, and into the gastric and intestinal lumen. Luminal somatostatin may affect other endocrine and nonendocrine cells in the mucous membrane of the gut. It is noted that the same stimulatory agent does not always stimulate somatostatin release from different organs; one agent stimulates the release from one organ and suppresses release from the other organ.

A Novel Variant of Ionotropic Glutamate Receptor Regulates Somatostatin Secretion From δ-Cells of Islets of Langerhans

“…When the islets were first incubated with 16.7 mmol/l glucose and then transferred to 3.3 mmol/l glucose (i.e., low-glucose stimulation), somatostatin secretion was significantly enhanced, corresponding to 147% of that with 16.7 mmol/l glucose throughout. Thus, high-and lowglucose stimulation enhanced somatostatin secretion, as has been observed in previous studies (3,15). Under similar assay conditions, the secretion of insulin and glucagon was enhanced by high-and low-glucose stimulation, respectively, indicating a well-known islet cellϪspecific response to glucose (Fig.…”

“…The inhibition is mediated through somatostatin receptor (SSTR)-1 and -5 in ␤-cells and SSTR-2 in ␣-cells (16 -18). Given that the mechanism underlying glucose sensing by ␦-cells is similar, if not identical, to that of ␤-cells, somatostatin secretion is upregulated by high blood glucose via cytosolic Ca 2ϩ and cAMP (3,15,19). Somewhat paradoxically, the lowering of blood glucose levels also enhances somatostatin secretion 1 and 3) and isolated islets (lanes 2 and 4).…”

“…Somatostatin, a tetradecapeptide, is a potent paracrine modulator that inhibits the secretion of insulin and glucagon from islets (3,14,15). The inhibition is mediated through somatostatin receptor (SSTR)-1 and -5 in ␤-cells and SSTR-2 in ␣-cells (16 -18).…”

“…The amplified product, which has the expected molecular weight, is indicated by an arrow. (15,20). Although somatostatin secreted under low-glucose conditions might be responsible for somatostatinevoked inhibition of glucagon secretion, it is unknown how low glucose enhances somatostatin secretion.…”

The microanatomy of human islets of Langerhans, with special reference to somatostatin (D-) cells.

“…Three mechanisms have been delineated for the influence of somatostatin on the secretory activity of the other endocrine cell types in the islets RcI et al, 1974;ORcI, 1976;UNGER and ORCI, 1976;FORSSMANN et al, 1978;UNGER et al, 1978;ORcI and PERRELET, 1979;EFENDIC et al, 1980;LARSSON, 1980;SCHAUDER, 1980;ARIMURA and FISHBACK, 1981;HONEY et al, 1981): a) membrane specializations (gap and tight junctions), b) secretion into the intercellular space, the "Parakrinie" of FEYRTER (1953), and c) secretion into the capillaries (endocrine route). The apparent interposition of D-cells between the A-cells and B-cells, at first reported in rodent islets and later on also for human islets, favored the hypothesis of a prevailing paracrine mode of action of D-cells (ORcI and UNGER,1975;LINGER andORcI, 1977, 1981a, b).…”