Determination of immunoreactive somatostatin in rat plasma and responses to arginine, glucose and glucagon infusion

Abstract

A method for the determination of immunoreactive somatostatin in rat plasma is described. Blood specimens were collected into aprotinin and EDTA. Plasma was separated, immediately diluted with acidified acetone and ultrasonicated. The resultant supernatant was lyophilised. The dilution curve of the material thus extracted was parallel to that of synthetic somatostatin. The material was eluted mainly in a similar position to that of synthetic somatostatin on Sephadex G-25(0 column chromatography. The somatostatin immunoreactivity was degraded significantly from the pre-incubated value of 846 + 86 pg/ml (n = 4, mean _+ SEM) to 102 __ 16 pg/ml in the same manner as that of synthetic somatostatin when incubated with one ml of fresh rat plasma at 37 ~ for 30 min. The mean recovery in quadruplicate of immtmoreacfive somatostatin at concentrations of 100, 200 and 400 pg/ml was 83 ___ 7, 95 ___ 4 and 76 ___ 4%, respectively. Using this method, plasma immunoreactive somatostatin responses to arginine, glucose and glucagon infusion were measured in pentobarbital anaesthetized rats. The mean basal plasma immtmoreactive somatostatin concentration in the jugular vein was 35 + 3 pg/ml (n = 7), while that in the hepatic portal vein was 120 + 17 pg/ml (n = 7). Infusion of arginine, glucose and glucagon all resulted in 2-3 fold increases in portal plasma immunoreactive somatostatin concentration.

Delta cell secretory responses to insulin secretagogues are not mediated indirectly by insulin

“…Glucagon stimulates somatostatin secretion in a number of experimental models, including isolated rodent islets [22], perfused canine [23] or human pancreas [25], and in rats in vivo [36]. The glucagon receptor has been detected in a subpopulation of primary delta cells by immunohistochemical analysis (∼11% vs 97% in beta cells [53]), although it is unclear whether this relatively low abundance is sufficient to account for the enhancing effect of glucagon on somatostatin secretion.…”

Circulating prosomatostatin-derived peptides. Differential responses to food ingestion.

“…Tyr'4-S-28 [1][2][3][4][5][6][7][8][9][10][11][12][13][14], Tyr'-S-14, and Tyr"-S-14 were purchased from Peninsula Laboratories, San Carlos, CA. S-14, S-13, S-12, and analogues of S-14 in which alanine or tyrosine was substituted for residues at the 5, 6, 8, and 10 positions were gifts from Dr. J. Rivier, Salk Institute, La Jolla, CA.…”

“…Because S-14 is secreted from cells that are widely distributed, notably in the central and peripheral nervous systems, pancreas, and GI tract (3)(4)(5)(6), the prevailing belief is that it acts on adjacent cells to modulate the release of specific secretory products (7,8). On the other hand, somatostatin-like immunoreactivity (SLI) is present in mammalian plasma (9)(10)(11)(12)(13), and rises after ingestion of nutrients or infusion of supraphysiologic doses of neurotransmitters and selected GI peptides (14)(15)(16)(17)(18)(19). From immune neutralization studies in dogs and S- 14 infusions into man mimicking postprandial levels of SLI, Schusdziarra et al (20) and Zyznar and colleagues (21), postulated that circulating S-14 acts as a hormone that may be involved in nutrient assimilation.…”

“…On the other hand, somatostatin-like immunoreactivity (SLI) is present in mammalian plasma (9)(10)(11)(12)(13), and rises after ingestion of nutrients or infusion of supraphysiologic doses of neurotransmitters and selected GI peptides (14)(15)(16)(17)(18)(19). From immune neutralization studies in dogs and S- 14 infusions into man mimicking postprandial levels of SLI, Schusdziarra et al (20) and Zyznar and colleagues (21), postulated that circulating S-14 acts as a hormone that may be involved in nutrient assimilation.…”

“…These include somatostatin-28 (S-28), a 28-amino acid-containing peptide incorporating S- 14 at its COOH-terminus, S-14, and des-Ala S-14(S-13) (23). Because pro-S is processed to either S-28 or S-14 in different cells (24)(25)(26), it is plausible that they fulfill divergent roles.…”