Effect of Ingested Nutrients on the Release of Thrittene into the Human Circulation

Abstract

Thrittene is a recently described peptide with a sequence homologous with somatostatin-28 ((1-13)) but is produced independent of the preprosomatostatin gene. It is localized in epithelial cells in stomach and gut mucosal crypts and in neuronal cell bodies in the myenteric plexus and enteric axons. It is also present in human plasma. The aim of this study was to determine whether the release of thrittene into the circulation was affected by the ingestion of nutrients and, if so, whether the pattern of release was distinct from the closely related peptide somatostatin-28 (S-28). Thrittene was indirectly measured in human plasma by an RIA using antiserum F4. F4 interacts with the Asn(5)-Pro(6) region shared by S-28 and thrittene. The contribution of S-28 to F4 immunoreactivity (F4-IR) was determined using a specific two-site assay, and this measure was subtracted from the total F4-IR to give an estimate of thrittene levels. Plasma for assay was taken from healthy men on 4 separate days before and after intake of: a mixed meal (715 kcal), and meals containing primarily fat (25 g; 225 kcal), carbohydrate (100 g; 454 kcal), and protein (22 g; 100 kcal). After the mixed meal, both S-28 and thrittene rose by 50-100% within 30 min and gradually declined by 4 h. These increments were mimicked after ingestion of fat. By contrast, thrittene levels increased after carbohydrate but not protein intake, whereas S-28 concentrations rose after protein but not carbohydrate ingestion. These findings indicate that thrittene is secreted into the mammalian circulation during food intake and raise the possibility that thrittene may play a role in nutrient disposition. The dichotomy in responses of thrittene and S-28 to ingestion of the major macronutrients suggests that they are secreted from different gastrointestinal cells.

Classification and functions of enteroendocrine cells of the lower gastrointestinal tract

“…found that somatostatin concentration and mRNA expression within the rat colon increased after 48 h of fasting (Ensinck et al. 1990; Ensinck et al. 2002, 2003; Kido et al.…”

Review article: somatostatin analogues in the treatment of gastroenteropancreatic neuroendocrine (carcinoid) tumours

“…The majority of circulating SST originates from the stomach and intestine, with plasma levels of 30–100 ρmol/mL which increase postprandially by ∼100% up to 2 h 28,29 . However, in general, SST effects are local and produced mainly at the specific site of secretion where it acts at nanomolar concentrations, prior to rapid inactivation by local endosomal endopeptidases (e.g.…”

“…23,27 Finally, it became apparent that SST was a pan inhibitory agent for all known gastrointestinal tract hormones. 23 The majority of circulating SST originates from the stomach and intestine, with plasma levels of 30-100 qmol ⁄ mL which increase postprandially by 100% up to 2 h. 28,29 However, in general, SST effects are local and produced mainly at the specific site of secretion where it acts at nanomolar concentrations, prior to rapid inactivation by local endosomal endopeptidases (e.g. endothelin-converting enzyme-1), 30 thereby minimizing superfluous systemic effects.…”

Biological redundancy of endogenous GPCR ligands in the gut and the potential for endogenous functional selectivity

“…Thrittene-like immunoreactivity has been detected in enteroendocrine cells and enteric neurons and this distribution is distinct to that for SST-14 and SST-28 ( Ensinck et al, 2002 ). This is supported by the differential release of thrittene and SST in response to feeding ( Ensinck et al, 2003 ). Antrin expression was originally believed to be restricted to gastric D-cells, where it is localized to SST-28(1–12) containing secretory granules ( Ravazzola et al, 1989 ; Benoit et al, 1990 ).…”

“…Another endogenous peptide that shares extensive sequence homology with SST is thrittene [SST28(1–13)]. As with CST, thrittene is not derived from PSST and is a product of a distinct gene, as supported by the presence of thrittene-like immunoreactivity in PSST deficient mice ( Ensinck et al, 2003 ). Moreover, thrittene and SST are expressed by distinct cell populations and their release is triggered in response to different stimuli ( Ensinck et al, 2002 ).…”