Distribution and characterisation of immunoreactive somatostatin in human gastrointestinal tract

Penman, Erica; Wass, John; Butler, Melissa G.; Penny, Elizabeth S.; Price, Janet E.; Wu, Ping; Rees, Lesley

doi:10.1016/0167-0115(83)90281-1

Cited by 121 publications

(55 citation statements)

References 26 publications

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“…Somatostatin-28 is the terminal peptide processed from prosomatostatin in the epithelial cells of the ileum and colon, whereas somatostatin-14 is the final product in most gastric, duodenum, and proximal jejunum D cells (48,49). We have measured plasma cortistatin for the first time, and its levels were higher than those obtained for somatostatin-14.…”

Section: Discussionmentioning

confidence: 97%

Somatostatin Molecular Variants in the Vitreous Fluid

et al. 2005

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OBJECTIVE -There is growing evidence to indicate that somatostatin could be added to the list of natural antiangiogenic factors that exist in the vitreous fluid. In addition, a deficit of intravitreous somatostatin-like immunoreactivity (SLI) has been found in diabetic patients with proliferative diabetic retinopathy (PDR). In the present study, we have determined the main molecular variants of somatostatin (somatostatin-14 and somatostatin-28) in the vitreous fluid and plasma of nondiabetic control subjects and diabetic patients with PDR. In addition, the contribution of cortistatin, a neuropeptide with strong structural similarities to somatostatin, to SLI and its levels in vitreous and plasma in both nondiabetic and diabetic patients has also been measured. RESERCH DESIGN AND METHODS-Plasma and vitreous fluid from 22 diabetic patients with PDR and 22 nondiabetic control subjects were analyzed. Somatostatin-14, somatostatin-28 and cortistatin were measured by radioimmunoassay but separation by highperformance liquid chromatography was required to measure somatostatin-14.RESULTS -The predominant molecular form of somatostatin within the vitreous fluid was somatostatin-28 (fivefold higher than somatostatin-14 in control subjects and threefold higher in patients with PDR). Cortistatin significantly contributed to SLI and its intravitreous levels were higher than those detected in plasma (nondiabetic control subjects: 147 vs. 78 [24 -32] pg/ml; patients with PDR: 187 vs. 62 [24 -472] pg/ml; P ϭ 0.01 for both). Intravitreous somatostatin-14 was similar in both subjects with PDR and the control group (P ϭ 0.87). By contrast, somatostatin-28 concentration was lower in patients with PDR than in nondiabetic control subjects (350 Ϯ 32 vs. 595 Ϯ 66 pg/ml; P ϭ 0.004).CONCLUSIONS -Somatostatin-28 is the main molecular variant in the vitreous fluid. The intravitreous SLI deficit detected in patients with PDR is mainly due to somatostatin-28. Cortistatin is abundant in the vitreous fluid and significantly contributes to SLI. These findings could open up new strategies for PDR treatment. Diabetes Care 28:1941-1947, 2005P roliferative diabetic retinopathy (PDR) represents a highly prevalent cause of visual loss in western countries and is the leading cause of new-onset blindness among people of working age (1). There is now ample evidence to suggest that the development of diabetic retinopathy is a multifactorial process in which it is not just the angiogenic factors alone but the balance between angiogenic and antiangiogenic factors that is crucial. Inhibition of angiogenesis has therefore become a target for the treatment of retinal neovascularization.Several pilot studies using the somatostatin analog octreotide in patients with early proliferative and severe non-PDR have revealed decreased incidence of progression into proliferative retinopathy needing panretinal laser treatment (2,3). In addition, the incidence of vitreous hemorrhage and the need for vitreoretinal surgery was also significantly reduced in octreotide-tr...

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Section: Discussionmentioning

confidence: 97%

Somatostatin Molecular Variants in the Vitreous Fluid

et al. 2005

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“…Intestinal enteroendocrine D cells containing Sst are scattered throughout the small and large intestine (11,46). Approximately 90% of intestinal Sst is present in the mucosa, whereas 10% is present in the muscular layer (44). Given that there is evidence suggesting that the Sst gene is differentially regulated in different populations of Sst-producing cells in the stomach (16,49), it would be of interest to investigate whether the same pancreasspecific TSE I and TSE II elements in the Sst gene promoter or other regulatory sequences mediate Pdx1 regulation in the proximal small intestine.…”

Section: Discussionmentioning

confidence: 99%

Pdx1inactivation restricted to the intestinal epithelium in mice alters duodenal gene expression in enterocytes and enteroendocrine cells

Chen

Fang²,

Davis

et al. 2009

American Journal of Physiology-Gastrointestinal and Liver Physi

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Null mutant mice lacking the transcription factor pancreatic and duodenal homeobox 1 (Pdx1) are apancreatic and survive only a few days after birth. The role of Pdx1 in regulating intestinal gene expression has therefore yet to be determined in viable mice with normal pancreatic development. We hypothesized that conditional inactivation of Pdx1 restricted to the intestinal epithelium would alter intestinal gene expression and cell differentiation. Pdx1 flox/flox; VilCre mice with intestine-specific Pdx1 inactivation were generated by crossing a transgenic mouse strain expressing Cre recombinase, driven by a mouse villin 1 gene promoter fragment, with a mutant mouse strain homozygous for loxP site-flanked Pdx1. Pdx1 protein is undetectable in all epithelial cells in the intestinal epithelium of Pdx1 flox/flox; VilCre mice. Goblet cell number and mRNA abundance for mucin 3 and mucin 13 genes in the proximal small intestine are comparable between Pdx1 flox/flox; VilCre and control mice. Similarly, Paneth cell number and expression of Paneth cell-related genes Defa1, Defcr-rs1, and Mmp7 in the proximal small intestine remain statistically unchanged by Pdx1 inactivation. Although the number of enteroendocrine cells expressing chromogranin A/B, gastric inhibitory polypeptide (Gip), or somatostatin (Sst) is unaffected in the Pdx1 flox/flox; VilCre mice, mRNA abundance for Gip and Sst is significantly reduced in the proximal small intestine. Conditional Pdx1 inactivation attenuates intestinal alkaline phosphatase (IAP) activity in the duodenal epithelium, consistent with an average 91% decrease in expression of the mouse enterocyte IAP gene, alkaline phosphatase 3 (a novel Pdx1 target candidate), in the proximal small intestine following Pdx1 inactivation. We conclude that Pdx1 is necessary for patterning appropriate gene expression in enterocytes and enteroendocrine cells of the proximal small intestine.

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“…Studies of GRP and NMB immunoreactivity as well as mRNA studies have demonstrated that these peptides and their mRNA are widely distributed in mammals in both the nervous system and peripheral tissues, especially the gastrointestinal tract (Penman et al, 1983;Wada et al, 1990;Battey and Wada, 1991;Spindel et al, 1993;Moody and Merali, 2004). In the alimentary tract GRP-like IR is found primarily in neurons as well as in the submucosal and myenteric plexuses and not in endocrine cells (Penman et al, 1983).…”

Section: Introductionmentioning

confidence: 99%