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

Abstract

Prosomatostatin (pro-S) and its bioactive posttranslational products, somatostatin-14 (S-14), somatostatin-13 (S-13), and somatostatin-28 (S-28), were measured in human plasma by the use of immunoglobulins to the NH2-terminus of S-28 conjugated with agarose to separate them and, thereafter, by RIA with an antiserum recognizing the COOH-terminus of pro-S, and by specific RIA for the NH2-terminus of S-14 and pro-S. In healthy men, mean basal levels of pro-S were 4 pg equivalent S-14/ml; S-14/S-13 combined were 9 pg equivalent S-14/ ml; and S-28 levels were 16 pg/ml. After a 700-kcal meal, pro-S, S-14, and S-14/S-13 did not change, whereas S-28 levels doubled by 120 min and remained elevated for 240 min. To evaluate the origins of these peptides, their levels were compared in peripheral, portal, gastric, and mesenteric veins of anesthetized patients and in patients with total resection of stomach and pancreas before and after nutrient intake. The stomach and small intestine were sources of both peptides; however, most S-28 originated in the small intestine. These findings suggest that, in contrast to S-14, S-28 is a hormone and may modulate postprandial nutrient absorption and use.

Endogenous somatostatin-28 modulates postprandial insulin secretion. Immunoneutralization studies in baboons.

“…The antibody was typed as IgG 1 by a mouse monoclonal isotyping kit (Amersham International, Little Chalfont, UK). Affinity and specificity were measured using S-14, S-28, and analogs of S-14 as reported previously (3 12 and 2.8 ϫ 10 11 mol/liter for S-14 and S-28, respectively. Plasma analyses.…”

“…By contrast, in addition to its ubiquitous distribution in the central nervous system (CNS), S-28 is synthesized selectively in endocrine cells of the gastric pylorus and upper gut (16), and plasma concentrations of this peptide are increased consistently and significantly after intake of nutrients (3,17). Thus, we hypothesized that S-28 is a regulator of glucose metabolism during the postprandial state.…”

“…1 and somatostatin-28 (S-28) are secreted into the blood stream and share the ability to inhibit the release of a variety of peptides and neurotransmitters (1)(2)(3). It has been held generally that S-14, which is processed from prosomatostatin (Pro-S) in D cells of the stomach and pancreas and in peripheral neurons, is a paracrine regulator of the release of several hormones and neuropeptides (1,2,(4)(5)(6)(7).…”

“…It has been held generally that S-14, which is processed from prosomatostatin (Pro-S) in D cells of the stomach and pancreas and in peripheral neurons, is a paracrine regulator of the release of several hormones and neuropeptides (1,2,(4)(5)(6)(7). Although it has also been postulated that S-14 acts as a hormone (8,9), this notion is problematic, since S-14 enters the circulation from diverse sources, its putative target organ is not obvious, and its peripheral plasma levels show little, if any, change after physiologic events such as nutrient intake (3). Further, studies by Stagner, Samols, and colleagues do not support an endocrine role for S-14 in pancreatic islets based on the lack of effect of antisomatostatin serum on insulin or glucagon levels when it was perfused through isolated pancreata from several species (10)(11)(12)(13).…”

Expression of receptors for gut peptides in human pancreatic adenocarcinoma and tumour-free pancreas

“…Tyr-B-ala-secretin and VIP-28 were iodinated using the Chloramine-T oxidation method. lodinated peptides were separated from unincorporated iodide by gel filtration on a Sephadex G25-F or G50-SF column pre-equilibrated with 0.1 N acetic acid and 0.1% gelatin or 0.25 M ammonium hydrogen carbonate (Schaffalitzky et al, 1976;Ensinck et al, 1989 ride, 5 mm magnesium chloride, 1 mM EGTA and 100 pM each radioligand at pH 6.0, 6.5, 7.0 and 7.5 separately for 180 min. Alternate slides were incubated with addition of 1 jiM of the corresponding non-radioactive peptides to determine the extent of nonspecific binding.…”