Le système nerveux autonome stimule la sécrétion d’aldostérone par le biais de la substance P chez l’homme

International audienc

Le système nerveux autonome stimule la sécrétion d’aldostérone par le biais de la substance P chez l’homme

International audienc

An Enteral Leucine Supply Modulates Human Duodenal Mucosal Proteome and Decreases the Expression of Enzymes Involved in Fatty Acid Beta-Oxidation

Leucine is well known to regulate protein metabolism in muscle. We recently reported that enteral leucine infusion decreased proteasome activity in human duodenal mucosa and enhanced intestinal cell proliferation, but its effects on gut proteome remain unknown. Therefore, we aimed to assess the effects of an enteral leucine infusion on the whole proteome of duodenal mucosa. In this work, 5 healthy volunteers received for 5h, on 2 occasions and in random order, an enteral supply of maltodextrins (0.25 g kg(-1) h(-1)) or maltodextrins supplemented with leucine (0.035 g kg(-1) h(-1)). At the end of infusion, endoscopic duodenal biopsy samples were collected and analyzed by 2D-PAGE. Eleven protein spots were differentially and significantly (P<0.05) expressed in response to the leucine-supplemented maltodextrins compared with maltodextrins alone. Forty percent of identified proteins by mass spectrometry were located in mitochondria. Four proteins were involved in lipid metabolism: HADHA, ACADVL and CPT2 expressions were reduced, whereas FABP1 expression was increased. In addition, the expression of DHA kinase involved in glycerol metabolism was also downregulated. Finally, leucine supplementation altered the duodenal mucosal proteome by regulating the expression of several enzymes mainly involved in lipid metabolism. These results suggest that leucine supplementation may slowdown fatty acid beta-oxidation in human duodenal mucosa

Octreotide SC depot in patients with acromegaly and functioning neuroendocrine tumors: a phase 2, multicenter study

Octreotide SC depot is a novel, ready-to-use formulation administered via a thin needle. In a phase 1 study in healthy volunteers, this formulation provided higher bioavailability of octreotide with faster onset and stronger suppression of IGF-1 in healthy volunteers versus long-acting intramuscular (IM) octreotide. This phase 2 study evaluated the pharmacokinetics, efficacy, and safety of octreotide SC depot in patients with acromegaly and functioning NETs, previously treated with octreotide IM

Effects of an Enteral Glucose Supply on Protein Synthesis, Proteolytic Pathways, and Proteome in Human Duodenal Mucosa

BACKGROUND: Previous studies have shown that the glucose supply reduces postoperative insulin resistance and improves patient outcomes. However, the effects of luminal glucose on intestinal mucosal proteins remain unknown. OBJECTIVE: We aimed to assess the effects of an enteral glucose supply on protein synthesis, proteolytic pathways, and proteome in human duodenal mucosa. DESIGN: Twenty healthy volunteers received a 5-h enteral infusion of either saline or glucose (0.12 g · kg(-1) · h(-1)). Simultaneously, a continuous intravenous infusion of l-[1-(13)C]leucine (12 μmol · kg(-1) · h(-1)) was maintained until endoscopy. The duodenal mucosal protein fractional synthesis rate (FSR) was calculated from leucine enrichments assessed in protein and free amino acid pools by gas chromatography-mass spectrometry. Cathepsin D, calpains, and chymotrypsin-like proteasome mucosal activities were evaluated by using specific fluorogenic substrates. A 2-dimensional PAGE-based comparative proteomics analysis was also performed on additional duodenal mucosal biopsy samples to identify differentially expressed proteins. RESULTS: Duodenal mucosal protein FSR and protease activities were not affected by glucose infusion relative to saline. Nevertheless, the comparative proteomics analysis indicated that 10 protein spots were significantly differentially expressed (ie, at least ±1.5-fold modulated; Student's t test, P < 0.05) in response to the glucose infusion relative to saline. Of the 8 proteins identified by mass spectrometry, α-enolase, cytoplasmic aconitate hydratase, and glutathione S-transferase ω-1 were upregulated, whereas epoxide hydrolase 2 was downregulated. CONCLUSION: Enteral glucose supply affected neither duodenal mucosal protein FSR nor activities of mucosal proteases but altered the duodenal mucosal proteome by modulating the expression of several enzymes involved mainly in carbohydrate and xenobiotic metabolism. This trial is registered at clinicaltrials.gov as NCT00213551

The neuropeptide substance P regulates aldosterone secretion in human adrenals

International audienceAldosterone, produced by the adrenals and under the control of plasma angiotensin and potassium levels, regulates hydromineral homeostasis and blood pressure. Here we report that the neuropeptide substance P (SP) released by intraadrenal nerve fibres, stimulates aldosterone secretion via binding to neurokinin type 1 receptors (NK1R) expressed by aldosterone-producing adrenocortical cells. The action of SP is mediated by the extracellular signal-regulated kinase pathway and involves upregulation of steroidogenic enzymes. We also conducted a prospective proof-of-concept, double blind, placebo-controlled clinical trial aimed to investigate the impact of the NK1R antagonist aprepitant on aldosterone secretion in healthy male volunteers (EudraCT: 2008-003367-40, ClinicalTrial.gov: NCT00977223). Participants received during two 7-day treatment periods aprepitant (125 mg on the 1st day and 80 mg during the following days) or placebo in a random order at a 2-week interval. The primary endpoint was plasma aldosterone levels during posture test. Secondary endpoints included basal aldosterone alterations, plasma aldosterone variation during metoclopramide and hypoglycaemia tests, and basal and stimulated alterations of renin, cortisol and ACTH during the three different stimulatory tests. The safety of the treatment was assessed on the basis of serum transaminase measurements on days 4 and 7. All pre-specified endpoints were achieved. Aprepitant decreases aldosterone production by around 30% but does not influence the aldosterone response to upright posture. These results indicate that the autonomic nervous system exerts a direct stimulatory tone on mineralocorticoid synthesis through SP, and thus plays a role in the maintenance of hydromineral homeostasis. This regulatory mechanism may be involved in aldosterone excess syndromes

Impact des mesures de soutien à l’exportation et de l’aide alimentaire sur la sécurité alimentaire

Ce rapport a été financé par la Commission européenne (DG Agriculture) ; Texte intégral (en PDF) accessible à l'adresse suivante : http://ec.europa.eu/agriculture/eval/reports/food_security/index_fr.htmAutres production

The effect of camelina oil on vascular function in essential hypertensive patients with metabolic syndrome: a randomized, placebo-controlled, double-blind study

International audienceBackground The effects of a dietary supplementation with the vegetable omega-3 α-linolenic acid (ALA) on cardiovascular homeostasis are unclear. In this context, it would be interesting to assess the effects of camelina oil. Objective This study aimed to assess the cardiovascular and metabolic effects of camelina oil in hypertensive patients with metabolic syndrome. Methods In a double-blind placebo-controlled randomized study, treated essential hypertensive patients with metabolic syndrome received during 6 months either cyclodextrin-complexed camelina oil containing ≈ 1.5 g ALA/day (n = 40), or an isocaloric placebo (n = 41), consisting in the same quantity of cyclodextrins and wheat starch. Anthropometric data, plasma lipids, glycemia, insulinemia, creatininemia, thiobarbituric acid reactive substances, high-sensitivity C-reactive protein, and n-3, n-6 and n-9 fatty acids in erythrocyte membranes were measured. Peripheral and central blood pressures, arterial stiffness, carotid intima-media thickness and brachial artery endothelium-dependent flow-mediated dilatation and endothelium-independent dilatation were assessed. Results Compared to placebo, camelina oil increased ALA (mean ± SD: 0 ± 0.04 vs. 0.08 ± 0.06%, P &lt; 0.001), its elongation product eicosapentaenoic acid (EPA; 0 ± 0.5 vs. 0.16 ± 0.65%, P &lt; 0.05), and the n-9 gondoic acid (0 ± 0.04 vs. 0.08 ± 0.04%, P &lt; 0.001). No between-group difference was observed for cardiovascular parameters. However, changes in flow-mediated dilatation were associated with the magnitude of changes in EPA (r = 0.26, P = 0.03). Compared to placebo, camelina oil increased fasting glycemia (–0.2 ± 0.6 vs. 0.3 ± 0.5 mmol/L, P &lt; 0.001) and homeostatic model assessment for insulin resistance (HOMA-IR; –0.8 ± 2.5 vs. 0.5 ± 0.9, P &lt; 0.01) index, without affecting plasma lipids, or inflammatory and oxidative stress markers. Changes in HOMA-IR index were correlated with the magnitude of changes in gondoic acid (r = 0.32, P &lt; 0.01). Nutritional intake remained similar between groups. Conclusion ALA supplementation with camelina oil did not improve vascular function but adversely affected glucose metabolism in hypertensive patients with metabolic syndrome Whether this adverse effect on insulin sensitivity is related to gondoic acid enrichment, remains to be elucidated

Enteral Delivery of Proteins Enhances the Expression of Proteins Involved in the Cytoskeleton and Protein Biosynthesis in Human Duodenal Mucosa

BACKGROUND: Amino acids are well known to be key effectors of gut protein turnover. We recently reported that enteral delivery of proteins markedly stimulated global duodenal protein synthesis in carbohydrate-fed healthy humans, but specifically affected proteins remain unknown. OBJECTIVE: We aimed to assess the influence of an enteral protein supply on the duodenal mucosal proteome in carbohydrate-fed humans. DESIGN: Six healthy volunteers received for 5 h, on 2 occasions and in random order, either an enteral infusion of maltodextrins alone (0.25 g · kg^-1 · h^-1) mimicking the fed state or maltodextrins with a protein powder (0.14 g proteins · kg^-1 · h^-1). Endoscopic duodenal biopsy specimens were then collected and frozen until analysis. A 2-dimensional polyacrylamide gel electrophoresis-based comparative proteomics analysis was then performed, and differentially expressed proteins (at least ±1.5-fold change; Student's t test, P < 0.05) were identified by mass spectrometry. Protein expression changes were confirmed by Western blot analysis. RESULTS: Thirty-two protein spots were differentially expressed after protein delivery compared with maltodextrins alone: 28 and 4 spots were up- or downregulated, respectively. Among the 22 identified proteins, 11 upregulated proteins were involved either in the cytoskeleton (ezrin, moesin, plastin 1, lamin B1, vimentin, and β-actin) or in protein biosynthesis (glutamyl-prolyl-transfer RNA synthetase, glutaminyl-transfer RNA synthetase, elongation factor 2, elongation factor 1δ, and eukaryotic translation and initiation factor 3 subunit f). CONCLUSIONS: Enteral delivery of proteins altered the duodenal mucosal proteome and mainly stimulated the expression of proteins involved in cytoskeleton and protein biosynthesis. These results suggest that protein supply may affect intestinal morphology by stimulating actin cytoskeleton remodeling