Regulatory Peptides[JOURNAL]
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200 papers
Lateral hypothalamic serotonin is not stimulated during central leptin hypophagia.
Telles MM, da Silva TG, Watanabe RL … +5 more , de Andrade IS, Estadella D, Nascimento CM, Oyama LM, Ribeiro EB
Regul Pept · 2013 Jun · PMID 23518461 · Publisher ↗
Whether leptin targets the hypothalamic serotonergic system to inhibit food intake is not established. We examined the effect of a short-term i.c.v. leptin treatment on serotonin microdialysate levels in rat lateral hypo...
Whether leptin targets the hypothalamic serotonergic system to inhibit food intake is not established. We examined the effect of a short-term i.c.v. leptin treatment on serotonin microdialysate levels in rat lateral hypothalamus. Adipose tissue gene expression was also evaluated. Male rats received four daily injections of leptin (5 μg) or vehicle (with pair-feeding to leptin-induced intake) and a fifth injection during collection of LH microdialysates. We found that serotonin and 5-HIAA levels were not affected by the leptin pre-treatment, as basal levels were similar between the leptin and the pair-fed group. These levels remained unaltered after the acute leptin injection. For gene expression studies, rats were pre-treated with five daily injections of either leptin (5 μg) or vehicle (with either pair-feeding or ad libitum intake). mRNA levels of resistin, adiponectin, lipoprotein lipase, and PPAR-gamma were unaltered by either leptin or pair-feeding. Leptin gene expression was significantly reduced by leptin but not by pair-feeding, in both the retroperitoneal (-74%) and the epididymal (-99%) depots while no differences were observed in the subcutaneous depot. The observations confirmed the absence of an acute stimulatory effect of central leptin on serotonin release in the lateral hypothalamus and showed that the pre-treatment with leptin failed to modify this pattern. This indicates that components of the serotonergic system are probably not directly affected by leptin. Additionally, the central effect of leptin was able to downregulate its own adipose tissue gene expression in a depot-specific manner while other adipokine genes were not affected.
PsT-1: a new tryptophyllin peptide from the skin secretion of Waxy Monkey Leaf Frog, Phyllomedusa sauvagei.
Wang R, Chen T, Zhou M … +2 more , Wang L, Shaw C
Regul Pept · 2013 Jun · PMID 23518460 · Publisher ↗
The Waxy Monkey Leaf Frog, Phyllomedusa sauvagei, has been extensively-studied for many years, and a broad spectrum of bioactive peptides has been found in its skin secretions. Here we report the discovery of a novel try...
The Waxy Monkey Leaf Frog, Phyllomedusa sauvagei, has been extensively-studied for many years, and a broad spectrum of bioactive peptides has been found in its skin secretions. Here we report the discovery of a novel tryptophyllin (TPH) peptide, named PsT-1, from this frog species. Skin secretions from specimens of P. sauvagei were collected by mild electrical stimulation. Peptides were identified and characterized by transcriptome cloning, and the structure was confirmed by MALDI-TOF mass spectrometry and automated Edman degradation. This novel peptide was encoded by a single precursor of 61 amino acid residues, whose primary structure was deduced from cloned skin cDNA. Analysis of different amphibian tryptophyllins revealed that PsT-1 exhibited a high degree of primary structural similarity to its homologs, PdT-1 and PdT-2, from the Mexican giant leaf frog, Pachymedusa dacnicolor. A synthetic replicate of PsT-1 was found to inhibit bradykinin-induced vasorelaxation of phenylephrine pre-constricted rat tail artery smooth muscle. It was also found that PsT-1 had an anti-proliferative effect on three different human prostate cancer cell lines (LNCaP/PC3/DU145), by use of an MTT assay coupled with direct cell counting as measures of cell growth. These data indicate that PsT-1 is a likely bradykinin receptor antagonist and its biological effects are probably mediated through bradykinin receptors. As a BK antagonist, PST-1, with antagonistic effects on BK in artery smooth muscle, inhibition of proliferation in prostate cancer cells and lack of undesirable side effects, may have potential in cardiovascular, inflammatory and anticancer therapy.
The effects of para-chloromercuribenzoic acid and different oxidative and sulfhydryl agents on a novel, non-AT1, non-AT2 angiotensin binding site identified as neurolysin.
Santos KL, Vento MA, Wright JW … +1 more , Speth RC
Regul Pept · 2013 Jun · PMID 23511333 · Full text
A novel, non-AT1, non-AT2 brain binding site for angiotensin peptides that is unmasked by p-chloromercuribenzoate (PCMB) has been identified as a membrane associated variant of neurolysin. The ability of different organi...
A novel, non-AT1, non-AT2 brain binding site for angiotensin peptides that is unmasked by p-chloromercuribenzoate (PCMB) has been identified as a membrane associated variant of neurolysin. The ability of different organic and inorganic oxidative and sulfhydryl reactive agents to unmask or inhibit 125I-Sar1Ile8 angiotensin II (SI-Ang II) binding to this site was presently examined. In tissue membranes from homogenates of rat brain and testis incubated in assay buffer containing losartan (10 μM) and PD123319 (10 μM) plus 100 μM PCMB, 5 of the 39 compounds tested inhibited 125I-SI Ang II binding in brain and testis. Mersalyl acid, mercuric chloride (HgCl2) and silver nitrate (AgNO3) most potently inhibited 125I-SI Ang II binding with IC50s ~1-20 μM. This HgCl2 inhibition was independent of any interaction of HgCl2 with angiotensin II (Ang II) based on the lack of effect of HgCl2 on the dipsogenic effects of intracerebroventricularly administered Ang II and 125I-SI Ang II binding to AT1 receptors in the liver. Among sulfhydryl reagents, cysteamine and reduced glutathione (GSH), but not oxidized glutathione (GSSG) up to 1mM, inhibited PCMB-unmasked 125I-SI Ang II binding in brain and testis. Thimerosal and 4-hydroxymercuribenzoate moderately inhibited PCMB-unmasked 125I-SI Ang II binding in brain and testis at 100 μM; however, they also unmasked non-AT1, non-AT2 binding independent of PCMB. 4-Hydroxybenzoic acid did not promote 125 I-SI Ang II binding to this binding site indicating that only specific organomercurial compounds can unmask the binding site. The common denominator for all of these interacting substances is the ability to bind to protein cysteine sulfur. Comparison of cysteines between neurolysin and the closely related enzyme thimet oligopeptidase revealed an unconserved cysteine (cys650, based on the full length variant) in the proposed ligand binding channel (Brown et al., 2001) [45] near the active site of neurolysin. It is proposed that the mercuric ion in PCMB and closely related organomercurial compounds binds to cys650, while the acidic anion forms an ionic bond with a nearby arginine or lysine along the channel to effect a conformational change in neurolysin that promotes Ang II binding.
Acute effects of continuous infusions of glucagon-like peptide (GLP)-1, GLP-2 and the combination (GLP-1+GLP-2) on intestinal absorption in short bowel syndrome (SBS) patients. A placebo-controlled study.
Madsen KB, Askov-Hansen C, Naimi RM … +5 more , Brandt CF, Hartmann B, Holst JJ, Mortensen PB, Jeppesen PB
Regul Pept · 2013 Jun · PMID 23511332 · Publisher ↗
BACKGROUND AND AIMS: The ileocolonic brake is impaired in short bowel syndrome (SBS) patients with distal bowel resections. An attenuated meal-stimulated hormone secretion may cause gastric hypersecretion, rapid gastric...
BACKGROUND AND AIMS: The ileocolonic brake is impaired in short bowel syndrome (SBS) patients with distal bowel resections. An attenuated meal-stimulated hormone secretion may cause gastric hypersecretion, rapid gastric and intestinal transit and a poor adaptation. Attempting to restore this ileocolonic brake, this study evaluated the acute effects of continuous intravenous administration of glucagon-like peptide (GLP) 1 and 2, alone or in combination, on gastrointestinal function in SBS patients. METHODS: SBS patients were admitted 4 times for identical 72-h balance studies, where infusions (1 pmol/kg/min) of GLP-1, placebo (saline), GLP-2 and GLP-1+2 (1 pmol/kg/min of each), were provided. Patients filled out a VAS questionnaire regarding subjective symptoms during treatments. Bone mineral content, body-weight and -composition were measured using DEXA scans. Blood glucose, insulin, pro insulin C-peptide and GLP concentrations were measured in relation to a standardized breakfast. RESULTS: Nine SBS patients (5 women/4 men, aged 52±11) were enrolled and completed the study; 7 had end-jejunostomies, 2 had 50% of colon-in-continuity. All treatments significantly reduced the fecal wet weight, energy, nitrogen, sodium and potassium losses compared to placebo. However, only GLP-2 containing treatments increased absolute absorption of wet weight and sodium. Only GLP-1+2 improved the hydrational status evaluated by DEXA increases in the fat mass and calculated total body weight. GLP-1 and GLP-1+2 reduced the post-prandial blood glucose levels. A tendency of nausea and reduced appetite was seen in relation to GLP-1 treatment, but this was ameliorated by the co-administration of GLP-2. CONCLUSION: GLP-1 decreased diarrhea and fecal excretions in SBS patients, but it seems less potent than GLP-2. The combination of GLP-1+2 numerically provided additive effects on intestinal absorption compared to either peptide given alone. Larger, long-term studies should further assess the potential of the glucagon-like peptides or analogs, alone or in combination, in the treatment of SBS patients.
WITHDRAWN: Highly efficient agonist-induced internalization of somatostatin SST2 receptor in mouse dorsal root ganglion and spinal cord: Molecular evidence for mechanism of somatostatin inhibits neuropathic pain.
Xiang Q, Wang CL, Song S … +1 more , Shi TJ
Regul Pept · 2013 Mar · PMID 23507148 · Publisher ↗
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Calcitonin gene-related peptide promotes the wound healing of human bronchial epithelial cells via PKC and MAPK pathways.
Zhou Y, Zhang M, Sun GY … +4 more , Liu YP, Ran WZ, Peng L, Guan CX
Regul Pept · 2013 Jun · PMID 23501044 · Publisher ↗
Calcitonin gene-related peptide (CGRP) is a 37-amino acid neuropeptide derived from the calcitonin gene. CGRP is widely distributed in the central and peripheral neuronal systems. In the lung, CGRP could modulate dendrit...
Calcitonin gene-related peptide (CGRP) is a 37-amino acid neuropeptide derived from the calcitonin gene. CGRP is widely distributed in the central and peripheral neuronal systems. In the lung, CGRP could modulate dendritic cell function, stimulate proliferation of alveolar epithelial cells and mediate lung injury in mice. In this study, we investigated the effect of CGRP on the wound healing of human bronchial epithelial cells (HBECs) in vitro. The results showed that CGRP accelerated the recovery of wound area of monolayer HBECs in a dose-dependent manner. CGRP inhibited the lipopolysaccharide-induced apoptosis in HBECs. The percentage of S phase and G2/M phase was increased in HBECs after CGRP treatment. CGRP upregulated the expression of Ki67 in a dose-dependent manner. Some pathway inhibitors were used to investigate the signal pathway in which CGRP was involved. We found out that PKC pathway inhibitor (H-7) and MAPK pathway inhibitor (PD98059) could partially attenuate the effect of CGRP, which indicated that CGRP might promote the wound healing of HBECs via PKC and/or MAPK dependent pathway by accelerating migration and proliferation, and inhibiting apoptosis.
A dose-equivalent comparison of the effects of continuous subcutaneous glucagon-like peptide 2 (GLP-2) infusions versus meal related GLP-2 injections in the treatment of short bowel syndrome (SBS) patients.
Naimi RM, Madsen KB, Askov-Hansen C … +5 more , Brandt CF, Hartmann B, Holst JJ, Mortensen PB, Jeppesen PB
Regul Pept · 2013 Jun · PMID 23501043 · Publisher ↗
OBJECTIVE: Glucagon-like peptide 2 (GLP-2), secreted endogenously from L-cells in the distal bowel in relation to meals, modulates intestinal absorption by adjusting gastric emptying and secretion and intestinal growth....
OBJECTIVE: Glucagon-like peptide 2 (GLP-2), secreted endogenously from L-cells in the distal bowel in relation to meals, modulates intestinal absorption by adjusting gastric emptying and secretion and intestinal growth. Short bowel syndrome (SBS) patients with distal intestinal resections have attenuated endogenous GLP-2 secretion, which may contribute to their rapid gastric emptying, gastric hypersecretion and poor intestinal adaptation, whereas SBS patients with preserved terminal ileum and colon, who have a constantly elevated GLP-2 secretion, seem to do better in these respects. This study compared effects of continuous, subcutaneous (s.c.), exogenous GLP-2 infusion (CONT-GLP-2) versus three daily s.c. GLP-2 injections (TID-GLP-2) on intestinal absorption in SBS patients. DESIGN: Eight SBS patients (5 F, 3 M; 60±7 years; remnant small bowel 111±62 cm; 1 with 50% colon) were studied. In an open-label, sequential study, the 72-hour baseline admission was followed by two dose-equivalent, 21-day, dosing regimens; CONT-GLP-2, providing 1.0mg/day by a MiniMed insulin pump and TID-GLP-2, providing 0.33 mg injections in relation to three meals, separated by a washout period of at least 3 weeks. During admissions, the intestinal absorption was evaluated by analysing a double portion of the diet, faecal and urinary excretions. Post-absorptive plasma citrulline, reflecting enterocyte mass, was measured by HPLC. RESULTS: Compared to baseline, both GLP-2 dosing regimens reduced diarrhoea (CONT-GLP-2: 749±815 g/d and TID-GLP-2: 877±1004 g/d, p=0.01) and increased wet weight absorption (CONT-GLP-2: 19±19% and TID-GLP-2: 25±21%, p=0.003). Significant increases in plasma citrulline (CONT-GLP-2: 7.5±7 μmol/L and TID-GLP-2, 12.7±8 μmol/L; p=0.001) suggesting intestinotrophic effects in relation to GLP-2 treatment, are followed by increases in relative absorption of energy, carbohydrate and fat. No significant difference was seen on any of the absorptive parameters measured between the two dosing regimens. CONCLUSION: Both GLP-2 regimens significantly reduced diarrhoea in SBS patients, but a significant difference between continuous GLP-2 administration and TID injections could not be detected in a study of this size.
Ghrelin-leptin network influences serum chitinase 3-like protein 1 (YKL-40) levels in obese prepubertal children.
Kyrgios I, Galli-Tsinopoulou A, Stylianou C
Regul Pept · 2013 May · PMID 23501042 · Publisher ↗
OBJECTIVE: This study aimed to investigate any possible interactions between hormonal regulators of weight gain and markers of subclinical inflammation in childhood obesity. Forty-one obese prepubertal children and 41 ag...
OBJECTIVE: This study aimed to investigate any possible interactions between hormonal regulators of weight gain and markers of subclinical inflammation in childhood obesity. Forty-one obese prepubertal children and 41 age- and gender-matched lean controls were included. Children were classified as obese or non-obese according to international age- and gender-specific body mass index (BMI) cutoff points defined by the International Obesity Task Force to define childhood obesity. Anthropometric measurements, serum insulin, chitinase 3-like protein (YKL-40), ghrelin and leptin levels as well as plasma glucose in the fasting state were determined. RESULTS: Obese children as compared with controls had higher YKL-40 (50.7±15.2 vs 41.0±10.5 ng/ml, p=0.003), higher leptin (33.8±16.0 vs 9.7±7.5 ng/ml, p<0.001) and lower ghrelin serum levels (871.4±368.0 vs 1417.6±387.3 pg/ml, p<0.001). The obese children with ghrelin levels above median (43.8±10.2 ng/ml) as compared to those with ghrelin below median (57.2±16.6 ng/ml) presented lower serum YKL-40 levels (p=0.009), indicating more severe inflammation with lower levels of ghrelin. By contrast, although the obese children with leptin levels above median (49.7±16.3 ng/ml) presented lower serum YKL-40 levels as compared to those with leptin levels below median (51.6±14.6 ng/ml), this difference did not reach the level of statistical significance (p=0.726). Moreover, serum YKL-40 levels were significantly correlated with ghrelin (r=-0.359, p=0.014) but not with leptin levels (r=0.169, p=0.261). A significant negative correlation between ghrelin and leptin levels was also found (r=-0.276, p=0.041). These findings remained unchanged for obese, when analyses were done separately, whereas the significance of correlations was lost for non-obese subjects. CONCLUSIONS: Ghrelin-leptin network had an impact on serum YKL-40 levels in obese prepubertal children; upregulation of YKL-40 secretion seems to be a consequence of reduced ghrelin rather than elevated leptin concentrations.
The localization of oxytocin receptors in the islets of Langerhans in the rat pancreas.
Suzuki M, Honda Y, Li MZ … +2 more , Masuko S, Murata Y
Regul Pept · 2013 May · PMID 23500836 · Publisher ↗
In this study, oxytocin receptors (OTRs) in the islets of Langerhans were detected using real-time RT-PCR and immunohistochemical technique. Indeed, OTR mRNA was expressed in the rat pancreas. Double immunohistochemical...
In this study, oxytocin receptors (OTRs) in the islets of Langerhans were detected using real-time RT-PCR and immunohistochemical technique. Indeed, OTR mRNA was expressed in the rat pancreas. Double immunohistochemical staining for OTR and either glucagon or insulin demonstrated their co-localization in A-cells or B-cells, respectively. OTR-immunoreactivity in A-cells was stronger than that of B-cells. All A-cells and 94.8% of B-cells were OTR-immunoreactive. We reveal the statistically significant relations of OTR with A-cells and B-cells in the islets of Langerhans. This is the first demonstration of the OTR localization in the islets of Langerhans immunohistochemically. It suggests that oxytocin (OT) is involved in the release of insulin and glucagon.
Antipyretic effect of central [Pyr1]apelin13 on LPS-induced fever in the rat.
Hatzelmann T, Harden LM, Roth J … +1 more , Gerstberger R
Regul Pept · 2013 Jun · PMID 23500835 · Publisher ↗
Intracerebroventricular (i.c.v.) injections of apelins have been shown to modulate the central control of cardiovascular function, as well as the homeostasis of fluid and salt balance, and to some extent also body core t...
Intracerebroventricular (i.c.v.) injections of apelins have been shown to modulate the central control of cardiovascular function, as well as the homeostasis of fluid and salt balance, and to some extent also body core temperature. Here, we investigated the effects of i.c.v. administration of [Pyr(1)]apelin13 (PyrAp13; 20nmol) dissolved in artificial cerebrospinal fluid (aCSF), as compared to aCSF alone, on fever and sickness behavior elicited in rats by intraperitoneal injection of bacterial lipopolysaccharide (LPS, 100 μg/kg). Injections of LPS induced a short phase of hypothermia followed by a biphasic fever, depression of motor activity, anorexia and adipsia. I.c.v. injections of PyrAp13 without systemic LPS application slightly augmented motor activity at statistically unaltered core temperature. In combination with LPS, central administration of PyrAp13 significantly reduced fever during the time period of 3-9h after injection, but did not significantly attenuate anorexia and adipsia, and had no effect on LPS-induced lethargy. Rats injected with PyrAp13 along with LPS showed a reduced level of LPS-induced circulating tumor necrosis factor-α (TNF-α). Primary neuroglial cultures established from the hypothalamic paraventricular nucleus (PVN) and the median preoptic nucleus (MnPO), brain sites being of major importance for central thermoregulation and also expressing the apelin receptor, were incubated with medium alone, medium containing LPS (100 μg/ml) or LPS plus PyrAp13 (10(-6) mol/L). Ninety minutes after start of the incubation, LPS alone but not LPS in combination with PyrAp13 (10(-6) mol/L) caused a significant elevation of TNF-α in the supernatants. The novel observation that PyrAp13 represents a centrally acting endogenous antipyretic peptide is discussed in relation to its capacity to modulate peripheral and central formation of TNF-α.
What difference exists in the pancreas of mammals with sanguivorous diet? A morphological, stereological and immunohistochemical study of the pancreatic islets of the hematophagous bat Diphylla ecaudata.
Machado-Santos C, Aquino JC, Mikalauka JS … +3 more , Abidu-Figueiredo M, Mendes RM, Sales A
Regul Pept · 2013 May · PMID 23500834 · Publisher ↗
Diphylla ecaudata is a vampire bat that mainly feeds on the blood of birds. This highly specialized diet - hematophagy - is accompanied by a series of morphological changes in the gastro-entero-pancreatic system, since t...
Diphylla ecaudata is a vampire bat that mainly feeds on the blood of birds. This highly specialized diet - hematophagy - is accompanied by a series of morphological changes in the gastro-entero-pancreatic system, since the distribution and relative proportions of different pancreatic endocrine cell types can vary between species due to different physiological conditions and eating habits. The aim of this study was to examine for the first time the pancreas of the vampire bat D. ecaudata using morphological, stereological and immunohistochemical techniques. The pancreas of the D. ecaudata has an exocrine acinar portion in which the highest concentration of pancreatic islets is scattered. These pancreatic islets have irregular size and a mean diameter of 56.94 μm. The total number of islets in the pancreas was 23,900, with a volumetric density of 4.1%. Insulin-immunoreactive (IR) cells were located in the central pancreatic islet region and had the largest density (54.8%). Glucagon-IR cells were located mainly in the peripheral mantle region (16.2%), along with somatostatin-IR (SS) cells (14.3%). Cells immunoreactive to insulin, glucagon and somatostatin were also observed to have spread in isolated places in the exocrine pancreas. In the connective tissue near the pancreatic ducts, a high concentration was identified of insulin-IR cells and a low concentration of glucagon-IR and somatostatin-IR cells. These results indicate that although the pancreas of D. ecaudata has morphological similarities with that of other mammals, it has a differentiated islet structure, because there were a large number of islets and different volumetric densities of α, β and δ cells.
In vitro and in vivo angiogenic activity of osteoarthritic and osteoporotic osteoblasts is modulated by VEGF and vitamin D3 treatment.
Neve A, Cantatore FP, Corrado A … +3 more , Gaudio A, Ruggieri S, Ribatti D
Regul Pept · 2013 Jun · PMID 23500833 · Publisher ↗
Vascular Endothelial Growth Factor (VEGF) is a potent angiogenic factor, which also regulates bone remodeling. Osteoblasts not only respond to VEGF stimulation, but also express and synthesize this factor. The present st...
Vascular Endothelial Growth Factor (VEGF) is a potent angiogenic factor, which also regulates bone remodeling. Osteoblasts not only respond to VEGF stimulation, but also express and synthesize this factor. The present study was aimed to evaluate in vitro differences in VEGF production and expression of cultured human osteoblastic cells derived from healthy donors and from subjects affected by osteoarthritis and osteoporosis, under basal conditions than after vitamin D3, and to investigate the angiogenic activity of culture media obtained by these cells in chick embryo chorioallantoic membrane (CAM) assay. The results showed that normal and pathological osteoblasts produce and express VEGF and 1,25 dihydroxy-vitamin D3 treatment increases protein and m-RNA VEGF levels. In addition culture media of pathological osteoblasts induce a strong angiogenic response, greater than observed with culture medium of normal cells, suggesting the involvement of osteoblast-derived VEGF in the pathogenesis of bone diseases.
Synthetic peptide octarphin (TPLVTLFK) inhibits the activity of the hypothalamus-pituitary-adrenal axis through nonopioid β-endorphin receptor.
Nekrasova YN, Zolotarev YA, Navolotskaya EV
Regul Pept · 2013 May · PMID 23499809 · Publisher ↗
The synthetic peptide octarphin (TPLVTLFK) corresponding to the sequence 12-19 of β-endorphin, a selective agonist of nonopioid β-endorphin receptor, was labeled with tritium to specific activity of 29 Ci/mmol. The analy...
The synthetic peptide octarphin (TPLVTLFK) corresponding to the sequence 12-19 of β-endorphin, a selective agonist of nonopioid β-endorphin receptor, was labeled with tritium to specific activity of 29 Ci/mmol. The analysis of [(3)H]octarphin binding to rat pituitary and adrenal cortex membranes revealed the existence of one type of binding sites (receptors): Kd 5.9 and 35.6 nM, respectively. Octarphin at concentrations of 1-1000 nМ was shown to inhibit the adenylate cyclase activity of rat adrenocortical membranes, while its intramuscular injection at doses of 10-100 μg/kg was found to reduce the secretion of corticosterone from the adrenals to the bloodstream. Thus, the nonopioid receptor of β-endorphin may be involved in the regulation of the activity of the pituitary and adrenal glands.
Perinatal malnutrition programs gene expression of leptin receptors isoforms in testis and prostate of adult rats.
Gombar FM, Ramos CF
Regul Pept · 2013 Jun · PMID 23499808 · Publisher ↗
The aim of this paper was to evaluate if maternal malnutrition during lactation programs the expression of leptin receptor isoforms in the testes and prostate ventral lobe of adult rats. At delivery, Wistar rats were sep...
The aim of this paper was to evaluate if maternal malnutrition during lactation programs the expression of leptin receptor isoforms in the testes and prostate ventral lobe of adult rats. At delivery, Wistar rats were separated into 3 groups: control group (C) with free access to a standard laboratory diet containing 22% protein; protein-energy restricted group (PER) with free access to an isoenergy and protein-restricted diet containing 8% protein; and energy-restricted group (ER) receiving standard laboratory diet in restricted quantities, which were calculated according to the mean ingestion of the PER group. All animals were sacrificed at 90 days of age. Both PER and ER groups presented low body weight from the first days after birth, however, while the ER group reached the control weight around day 80, the body weight of PER group was significantly lower compared to controls until the day the animals were killed. In relation to tissue weight, only the relative testis weight of the ER group presented an alteration compared to the control group (p<0.03). There was also no alteration in the leptin serum levels among the groups. The main leptin receptors isoforms, OBRa and OBRb were significantly increased in the testis (OBRa: C=0.71±0.10; PER=1.14±0.17; ER=1.92±0.70, p<0.0007, OBRb: C=0.87±0.04; PER=1.20±0.05; ER=1.44±0.17, p<0.001) and prostate (OBRa: C=0.70±0.18; PER=1.30±0.14; ER=1.65±0.22, p<0.014, OBRb: C=0.77±0.14; PER=1.16±0.04; ER=1.30±0.13, p<0.027) of both malnourished groups. However, the testis OBRc (C=1.52±0.06; PER=1.35±0.23; ER=3.50±0.72, p<0.023) and OBRf (C=1.31±0.12; PER=1.66±0.27; ER=3.47±0.55, p<0.009) and prostate OBRc (C=0.48±0.13; ER=1.18±0.34, p<0.01) and OBRf (C=0.73±0.15; PER=0.99±0.11; ER=1.83±0.30, p<0.016) isoforms were significantly increased only in the ER group. The results presented here show for the first time that both testis and prostate leptin receptor isoforms gene expression are programmed by perinatal malnutrition. These data further stress the importance of monitoring maternal and neonatal status, as well as other pathophysiological situations, to combat the appearance of long-term diseases.
Plasma N-terminal pro-brain natriuretic peptide levels are positively correlated with pulmonary arterial pressure in atrial septal defect patients.
Li ZF, Zhou DX, Wang QB … +3 more , Pan WZ, Zhang L, Ge JB
Regul Pept · 2013 May · PMID 23499807 · Publisher ↗
N-terminal pro-brain natriuretic peptide (NT-proBNP), a pro-hormone secreted by the myocardium in response to various stimuli, was found to be correlated with several hemodynamic parameters in pulmonary hypertension asso...
N-terminal pro-brain natriuretic peptide (NT-proBNP), a pro-hormone secreted by the myocardium in response to various stimuli, was found to be correlated with several hemodynamic parameters in pulmonary hypertension associated with systemic sclerosis. We investigated plasma NT-proBNP levels and the relationships between NT-proBNP and several hemodynamic parameters in atrial septal defect (ASD) patients with or without pulmonary arterial hypertension (PAH). We found that plasma NT-proBNP level was significantly higher in PAH group compared with the control group (5495.4±388.4 pg/ml vs 4005.1±260.5 pg/ml, P<0.05). In a multiple regression model analysis, only mean pulmonary arterial pressure was an independent predictor of NT-proBNP (standardized coefficient=0.663, P=0.002). In the PAH group, only right atrial systolic pressure was found to be positively correlated with NT-proBNP, whereas other parameters were not found to be correlated with NT-proBNP. Our data suggests that NT-proBNP might also be a predictor of the severity of pulmonary hypertension in the ASD patients.
Acute peripheral administration of synthetic human GLP-1 (7-36 amide) decreases circulating IL-6 in obese patients with type 2 diabetes mellitus: a potential role for GLP-1 in modulation of the diabetic pro-inflammatory state?
Daousi C, Pinkney JH, Cleator J … +2 more , Wilding JP, Ranganath LR
Regul Pept · 2013 May · PMID 23499806 · Publisher ↗
BACKGROUND: To explore the effects of acute administration of GLP-1 and GIP on circulating levels of key adipocyte-derived hormones and gut-brain peptides with established roles in energy and appetite regulation, modulat...
BACKGROUND: To explore the effects of acute administration of GLP-1 and GIP on circulating levels of key adipocyte-derived hormones and gut-brain peptides with established roles in energy and appetite regulation, modulation of insulin sensitivity and inflammation. METHODS: Six obese male patients with diet-treated type 2 diabetes (T2DM) and 6 healthy lean subjects were studied. The protocol included 4 experiments for each participant that were carried out in randomised order and comprised: GLP-1 infusion at a rate of 1 pmol/kg/min for 4h, GIP at a rate of 2 pmol/kg/min, GLP-1+GIP and placebo infusion. Plasma leptin, adiponectin, IL-6, insulin, ghrelin and obestatin were measured at baseline, 15, 60, 120, 180 and 240 min following the start of infusion. RESULTS: Patients with T2DM had higher baseline IL-6 compared with healthy [day of placebo infusion: T2DM IL-6 mean (SEM) 1.3 (0.3) pg/ml vs 0.3 (0.1)pg/ml, p=0.003]. GLP-1 infusion in T2DM was associated with a significant reduction in circulating IL-6 [baseline IL-6 1.2 pg/ml vs IL-6=0.7 at 120 min, p=0.0001; vs IL-6=0.8 at 180 min, p=0.001]. There was no significant change in leptin, adiponectin, ghrelin or obestatin compared to baseline on all 4 experimental days in both groups. CONCLUSION: Short-term infusion of supraphysiological concentrations of GLP-1 in T2DM results in suppression of IL-6, a key inflammatory mediator strongly linked to development of obesity and T2DM-related insulin resistance. It remains to be confirmed whether GLP-1-based diabetes therapies can impact favourably on cardiovascular outcomes.
Cholecystokinin but not ghrelin stimulates mucosal bicarbonate secretion in rat duodenum: independence of feeding status and cholinergic stimuli.
Sjöblom M, Lindqvist R, Bengtsson MW … +2 more , Jedstedt G, Flemström G
Regul Pept · 2013 May · PMID 23499805 · Publisher ↗
Cholecystokinin (CCK) is an important regulator of food digestion but its influence on small intestinal secretion has received little attention. We characterized effects of CCK-8, ghrelin and some related peptides on duo...
Cholecystokinin (CCK) is an important regulator of food digestion but its influence on small intestinal secretion has received little attention. We characterized effects of CCK-8, ghrelin and some related peptides on duodenal HCO3(-) secretion in vivo and demonstrated CCK-induced calcium signaling in acutely isolated enterocytes. A segment of proximal duodenum with intact blood supply was cannulated in situ in anaesthetized rats. Mucosal HCO3(-) secretion was continuously recorded (pH-stat). Peptides were administrated to the duodenum by close intra-arterial infusion. Clusters of duodenal enterocytes were attached to the bottom of a perfusion chamber. The intracellular calcium concentration ([Ca(2+)]i) was examined by dual-wavelength imaging. CCK-8 (3.0, 15 and 60 pmol/kg,h) caused dose-dependent increases (p<0.01) in duodenal alkaline secretion in both overnight fasted and continuously fed animals. The CCK1R-antagonist devazepide but neither the CCK2R-antagonist YMM022 nor the melatonin MT2-selective antagonist luzindole inhibited the rise in secretion. Atropine decreased sensitivity to CCK-8. The appetite-related peptide ghrelin was without effect on the duodenal secretion in fasted as well as fed animals. Superfusion with CCK-8 (1.0-50 nM) induced [Ca(2+)]i signaling in acutely isolated duodenal enterocytes. After an initial peak response, [Ca(2+)]i returned to near basal values within 3-5min. Devazepide but not YMM022 inhibited this [Ca(2+)]i response. Low doses of CCK-8 stimulate duodenal alkaline secretion and induce enterocyte [Ca(2+)]i signaling by an action at CCK1 receptors. The results point to importance of CCK in the rapid postprandial rise in mucosa-protective duodenal secretion.
Arginine vasopressin remolds the spontaneous discharges disturbed by amyloid β protein in hippocampal CA1 region of rats.
Pan YF, Jia XT, Wang XH … +4 more , Chen XR, Li QS, Gao XP, Qi JS
Regul Pept · 2013 May · PMID 23499804 · Publisher ↗
Beta-amyloid peptide (Aβ) aggregated in the brain is the main pathological characteristic of Alzheimer's disease (AD), and a significant decrease in the concentration of arginine vasopressin (AVP) in the brain of AD pati...
Beta-amyloid peptide (Aβ) aggregated in the brain is the main pathological characteristic of Alzheimer's disease (AD), and a significant decrease in the concentration of arginine vasopressin (AVP) in the brain of AD patients has been reported. Our recent study shows that intracerebroventricular (i.c.v.) injection of AVP protects against Aβ-induced impairments of spatial learning and memory. However, it is still unclear whether the Aβ-induced cognitive deficit is involved in the alteration of central neuronal discharges, and further whether AVP can modulate the electrophysiological change induced by Aβ. The present study thus observed the effects of AVP, Aβ and AVP plus Aβ on the spontaneous discharges of hippocampal CA1 neurons in rats by using multi-channel extracellular recording technique. The results showed that: (1) the average frequency of spontaneous discharges was decreased by i.c.v. injection of 25 nmol Aβ(25-35); (2) 10 nmol AVP induced an increase in spike discharge in the hippocampal CA1 neurons; (3) pretreatment with 10 nmol AVP effectively reversed Aβ(25-35) induced suppression of spontaneous discharges in hippocampal CA1 region. These in vivo electrophysiological results indicate that AVP, as a hormone and neurotransmitter, can remold the spontaneous discharges disturbed by Aβ and counteract the deleterious effect of Aβ(25-35) on neural circuit, suggesting that the activation of central vasopressinergic system may play a beneficial role for the prevention and treatment of cognitive impairments in AD.
Different responses of galanin and calcitonin gene-related peptide to capsaicin stimulation on dorsal root ganglion neurons in vitro.
Li Y, Liu G, Li H … +2 more , Wang H, Liu Z
Regul Pept · 2013 Jun · PMID 23499803 · Publisher ↗
Both galanin (Gal) and calcitonin gene-related peptide (CGRP) are sensory neuropeptides which expressed in dorsal root ganglion (DRG) neurons and are involved in nociceptive processing. Capsaicin (CAP) influences nocicep...
Both galanin (Gal) and calcitonin gene-related peptide (CGRP) are sensory neuropeptides which expressed in dorsal root ganglion (DRG) neurons and are involved in nociceptive processing. Capsaicin (CAP) influences nociceptive processing via influencing the expression of sensory neuropeptides in primary sensory neurons. However, little is known about the alterations of Gal and CGRP expression at the same condition stimulated by CAP. In the present study, primary cultured DRG neurons were used to determine the different responses of Gal and CGRP to CAP stimulation. DRG neurons were cultured for 48 hours and then exposed to CAP (2 μmol/L), capsazepine (CPZ) (2 μmol/L) plus CAP (2 μmol/L), or extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitor PD98059 (10 μmol/L) plus CAP (2 μmol/L) for an additional 24hours. The DRG neurons were continuously exposed to culture media as a control. After that, the levels of Gal mRNA and CGRP mRNA of DRG neurons were determined using real time-PCR analysis. Gal and CGRP expression in situ was detected by an immunofluorescent labeling technique. The levels of phosphorylated-ERK1/2 (pERK1/2) protein were detected using a Western blot assay. The results showed that CAP evoked increases of Gal and its mRNA and decreases of CGRP and its mRNA in DRG neurons. Administration of either CPZ or PD98059 blocked the effects of CAP. These data indicate that Gal and CGRP shared different responses to CAP stimulation. Gal and CGRP may have different effects in nociceptive processing during neurogenic inflammation.
PTHrP is a novel mediator for TGF-β-induced apoptosis.
Cao Y, Zhang W, Gao X … +5 more , Zhang G, Falzon M, Townsend CM, Hellmich MR, Ko TC
Regul Pept · 2013 Jun · PMID 23499802 · Full text
Parathyroid hormone-related protein (PTHrP) is a polyhormone secretory protein that plays fundamental roles in the development and function of various tissues. Transforming growth factor (TGF)-β is an important tumor sup...
Parathyroid hormone-related protein (PTHrP) is a polyhormone secretory protein that plays fundamental roles in the development and function of various tissues. Transforming growth factor (TGF)-β is an important tumor suppressor that induces cell cycle arrest and apoptosis. Increased PTHrP expression has been implicated in TGF-β-induced growth inhibition in human hepatocellular carcinoma cells. However, whether PTHrP is involved in TGF-β-induced apoptosis remains unknown. Using Hep3B and HuH-7, two human hepatocellular carcinoma cell lines, the current study examined the hypothesis that TGF-β-induced apoptosis is mediated by the induction of PTHrP expression. We found that (1) TGF-β induces PTHrP mRNA expression, protein expression and secretion in a time-dependent fashion; (2) knockdown of PTHrP gene expression or neutralization of secreted PTHrP isoforms blocks TGF-β-induced apoptosis; and (3) TGF-β-induced PTHrP expression is Smad3-dependent. Thus, we have identified PTHrP as a novel mediator for TGF-β-induced apoptosis in Hep3B cells. Our findings provide further insights into the mechanisms through which TGF-β conveys tumor suppression activity.
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