Secretion Of Other Peptides Research Articles

Role of Somatostatin in the Regulation of Central and Peripheral Factors of Satiety and Obesity.

Obesity is one of the major social and health problems globally and often associated with various other pathological conditions. In addition to unregulated eating behaviour, circulating peptide-mediated hormonal secretion and signaling pathways play a critical role in food intake induced obesity. Amongst the many peptides involved in the regulation of food-seeking behaviour, somatostatin (SST) is the one which plays a determinant role in the complex process of appetite. SST is involved in the regulation of release and secretion of other peptides, neuronal integrity, and hormonal regulation. Based on past and recent studies, SST might serve as a bridge between central and peripheral tissues with a significant impact on obesity-associated with food intake behaviour and energy expenditure. Here, we present a comprehensive review describing the role of SST in the modulation of multiple central and peripheral signaling molecules. In addition, we highlight recent progress and contribution of SST and its receptors in food-seeking behaviour, obesity (orexigenic), and satiety (anorexigenic) associated pathways and mechanism.

Somatostatin receptor agonists and antagonists

Somatostatin is a cyclic peptide that is widely distributed in the CNS, the periphery and in a variety of tumours. Two biologically active forms, somatotropin release-inhibiting factor (SRIF)-14 and SRIF-28, exert their effects through activation of five G-protein-coupled receptor subtypes (sst1 – sst5). These peptides act as neurotransmitters or hormones and inhibit the secretion of other peptides, such as insulin, growth hormone and glucagon. Metabolically stable peptide and structurally diverse non-peptide analogues have been developed as subtype-selective agonists and antagonists. The availability of these novel SRIF analogues will greatly facilitate our understanding of the function and role of specific SRIF receptors. SRIF analogues offer therapeutic potential in the regulation of hormone secretion, diseases of the CNS and periphery and in the treatment and diagnosis of various tumours. This review will focus on an overview of SRIF, new developments related to SRIF role and function and the discovery of novel peptide and non-peptide agonists and antagonists.

Evidence for biosynthesis of preproinsulin in gut of rat.

Glucagon and other pancreatic peptides are made in the gut, but there is little evidence for the formation of insulin. The demonstration of insulin receptors on the mucosa of gut epithelium suggests that there may be an autocrine or paracrine role for insulin made in the gut. Such insulin may control cell division, the secretion of other peptides from the same or neighboring cells, or motility and absorption. To search for the ability of the gut to make insulin, sections of freshly excised segments of rat gut were treated with an antiserum against porcine insulin. Intracellular immunoreactivity appeared in glandular cells in the stomach and colon but not in the small intestine. Preproinsulin mRNA was detected in similar cells in the stomach and colon by in situ hybridization, using specific oligonucleotide probes. Rat preproinsulin 1 and 2 mRNAs were transcribed by reverse transcriptase to the corresponding cDNAs, which were then amplified by polymerase chain reaction, utilizing specific oligonucleotide primers. Restriction analysis confirmed the identity of rat preproinsulin 1 and 2 mRNA in the colon and rat preproinsulin 1 mRNA in the stomach. Neither was found in the small intestine. Base sequences of the cDNAs were identical to the coding regions of pancreatic rat preproinsulin 1 and 2 messages. These observations are strong evidence for the synthesis of preproinsulin in the gut of the rat.

Effect of fibrostatin C, an inhibitor of prolyl 4-hydroxylase, on collagen secretion by human Tenon's capsule fibroblasts in vitro.

To investigate the effect of fibrostatin C, a prolyl 4-hydroxylase (PH) inhibitor produced by Streptomyces catenulae subsp. griseospora, on type I collagen secretion by human Tenon's capsule fibroblasts (TCFs) in vitro, as an indication of the potential therapeutic efficacy of this compound in antifibrotic therapy after glaucoma filtering surgery. The concentrations of type II procollagen COOH-terminal peptide (PIP) in culture medium or cell lysate were determined by immunoassays. For comparison with its effect on PIP secretion, we determined the effects of the agent on the secretion of other peptides, including laminin, vitronectin receptor, and a metalloproteinase inhibitor. The expression of collagens I and III, fibronectin, and PH by TCFs was examined by immunohistochemistry, and cellular ultrastructure was evaluated by transmission electron microscopy. Fibrostatin C (50 microM) significantly reduced the concentration of PIP in culture medium and increased its concentration in the cell lysate in a dose-dependent manner, but it had no effect on the secretion of other peptides. Cell viability and proliferation were not affected by fibrostatin C. Fibrostatin C also increased the number of cytoplasmic granules immunoreactive with antibodies to collagen I or III, but had no effect on fibronectin or PH immunoreactivity. Ultrastructurally, cisternae of the endoplasmic reticulum were dilated in fibrostatin C-treated TCFs, consistent with the retention of underhydroxylated collagen precursors in this organelle. Fibrostatin C inhibits the secretion of type I collagen by cultured TCFs. This agent may thus prove therapeutically beneficial for inhibiting the excess fibrosis in the wound of filtering surgery.

Growth hormone secretion by human peripheral blood mononuclear cells detected by an enzyme-linked immunoplaque assay.

In order to evaluate the secretion of GH from human peripheral blood mononuclear cells (PBMC) and its possible role as a modulator of lymphoproliferation, we have developed a hormonal enzyme-linked immunoplaque assay. This assay captures GH between a monoclonal and polyclonal antibody. This is followed by adding substrate and a horseradish peroxidase-conjugated antibody against the polyclonal antibody which produces violet colored plaques where GH has been secreted. This assay is sensitive, specific, highly reproducible, and can detect picogram quantities of GH. Using this assay we have detected GH secretion from approximately 1% of human PBMC under unstimulated conditions. Regression analysis showed a linear relationship between the number of cells plated and the number of GH plaques formed. Therefore, GH plaques were formed by single cells or its progeny and did not represent aggregation of secreting cells. Preincubation of PBMC with cycloheximide, a protein synthesis inhibitor, completely abolished the formation of GH plaques which suggests that the PBMC were responsible for the synthesis of the secreted GH. In addition, we have also observed that stimulation of human PBMC with T-cell mitogens, Concanavalin A and PHA and the cytokine IL-2 led to significant increases in GH plaque area and number whereas stimulation with LPS, a B cell mitogen, was ineffective. The PHA and IL-2 induced increase in plaque number suggests that they can recruit noncommitted lymphocytes to actively secrete GH which raises the possibility that this secreted GH may serve as a growth factor in T cell proliferation. We conclude that this immunoplaque assay may be useful in evaluating the secretion of other peptides from human immune cells.