scholarly journals Digestive and metabolic effects of potato and maize fibres in human subjects

1997 ◽  
Vol 77 (1) ◽  
pp. 33-46 ◽  
Author(s):  
C. Cherbut ◽  
A.-C. Aube ◽  
N. Mekki ◽  
C. Dubois ◽  
D. Lairon ◽  
...  
Keyword(s):  
Transit Time ◽  
Binding Capacity ◽  
Human Subjects ◽  
Chemical Properties ◽  
Basal Diet ◽  
Metabolic Effects ◽  
Healthy Human ◽  
Water Binding ◽  
Blood Concentrations

The physiological effects of dietary fibres in humans are due to their physico-chemical properties. However, it is difficult to predict these effects simply by measuring certain characteristicsin vitro. Studies in human subjects are still required to assess the effectiveness of new substrates. The aim of the present study in healthy human subjects was to evaluate the effects of two novel fibres, potato (PF) and maize (MF), on fasting and postprandial blood concentrations of carbohydrate and lipid metabolites as well as on stool ouput and transit time. The chemical composition, water-binding capacity (WBC) and fermentative properties of the fibres were also characterized in order to determine their possible involvement in digestive and metabolic effects. Stools, as well as breath and blood samples, were collected after consumption for 1 month of either a basal diet (control) or a basal diet supplemented with fibre (15 g/d). MF resisted fermentation better than PF and had lower digestibility. However, both fibres increased faecal output of dry matter, neutral sugars and water. There was an inverse relationship between stool weight and orofaecal transit time, although only MF significantly reduced transit time. Orocaecal transit was lengthened by PF, probably because of its high WBC. PF ingestion also decreased postprandial plasma levels of total and esterified cholesterol but had no effect on fasting concentrations. In contrast, MF lowered fasting cholesterolaemia and increased free:esterified cholesterol. These particular physiological and fermentative properties suggest that PF and MF would be suitable ingredients in a healthy diet.

Acute peripheral tissue effects of ghrelin on interstitial levels of glucose, glycerol, and lactate: a microdialysis study in healthy human subjects

2013 ◽  
Vol 304 (12) ◽  
pp. E1273-E1280 ◽  
Author(s):  
Esben Thyssen Vestergaard ◽  
Niels Møller ◽  
Jens Otto Lunde Jørgensen
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Human Subjects ◽  
Systemic Exposure ◽  
Metabolic Effects ◽  
Controlled Study ◽  
Healthy Human ◽  
Adipose Tissues ◽  
Ghrelin Receptor ◽  
Basal Period

Ghrelin is a gut-derived peptide and an endogenous ligand for the ghrelin receptor. Intravenous infusion of ghrelin induces insulin resistance and hyperglycemia and increases circulating levels of nonesterified free fatty acids. Our objective was to investigate whether the metabolic effects are mediated directly by ghrelin in skeletal muscle and adipose (peripheral and central) tissues. Ten healthy men (24.9 ± 1.3 yr) received 300 min of supraphysiological ghrelin administration by microdialysis catheters in skeletal muscle and adipose tissues in a randomized, single-blind, and placebo-controlled study. Microdialysis perfusates were analyzed every 30 min for glucose, glycerol, and lactate during both a basal period and a hyperinsulinemic euglycemic clamp. The primary outcome measures were interstitial concentrations of glucose, glycerol, and lactate in skeletal muscle and adipose tissues. Interstitial concentrations of glucose were similar in skeletal muscle, peripheral, and central adipose tissue in the basal period. During hyperinsulinemia, interstitial concentrations of glucose in skeletal muscle decreased in response to ghrelin exposure [2.84 ± 0.25 (ghrelin) vs. 3.06 ± 0.26 mmol/l (placebo), P = 0.04]. Ghrelin exposure did not impact on interstitial concentrations of glycerol and lactate. We conclude that ghrelin administration into skeletal muscle decreases interstitial concentrations of glucose during euglycemic hyperinsulinemia, which is indicative of increased insulin sensitivity without any effects on interstitial glycerol levels in either muscle or adipose tissue. These data contrast with the metabolic effects of ghrelin observed after systemic exposure and suggest the existence of a second messenger that remains to be identified.

Adrenomedullin: A Hypotensive Hormone in Man

1997 ◽  
Vol 92 (5) ◽  
pp. 467-472 ◽  
Author(s):  
John G. Lainchbury ◽  
Garth J. S. Cooper ◽  
David H. Coy ◽  
Ning-Yi Jiang ◽  
Lynley K. Lewis ◽  
...  
Keyword(s):  
Arterial Pressure ◽  
Human Subjects ◽  
Randomized Study ◽  
Plasma Concentrations ◽  
Urine Volume ◽  
Systolic Arterial Pressure ◽  
Peptide Hormone ◽  
Mean Difference ◽  
Healthy Human

1. Adrenomedullin, a recently discovered 52-amino-acid peptide hormone, circulates in plasma at low picomolar levels in man. Animal studies and studies in vitro indicate that it has diverse biological actions, including vasodilatation, natriuresis and diuresis, and positive inotropism as well as antiproliferative effects. We investigated the bioactivity of two doses of adrenomedullin in healthy human subjects. 2. Human adrenomedullin was given intravenously to eight male subjects at 2 and 8 ng min−1 kg−1, and haemodynamic, hormonal, renal and biochemical responses were recorded in a placebo (vehicle)-controlled, randomized study. 3. Compared with vehicle, adrenomedullin reduced mean arterial pressure (P = 0.05 for duration of infusion, mean difference at end of infusion 7.7 mmHg), systolic arterial pressure (P = 0.04 for duration of infusion, mean difference at end of infusion 10.7 mmHg) and at the lower dose reduced diastolic arterial pressure (P = 0.05 for lower dose, mean difference at end of infusion 6.3 mmHg) in the absence of compensatory responses in sympathetic activity or renin release. Urine volume and electrolyte excretion were unaffected. 4. The threshold for biological activity of adrenomedullin in man is lower for arterial pressure than for renal or hormonal responses, and is evident at plasma concentrations seen in disorders of the circulation. Adrenomedullin may be an important hormone under pathophysiological circumstances.

scholarly journals Activation of Coagulation by Administration of Recombinant Factor VIIa Elicits Interleukin 6 (IL-6) and IL-8 Release in Healthy Human Subjects

2003 ◽  
Vol 10 (3) ◽  
pp. 495-497 ◽  
Author(s):  
Evert de Jonge ◽  
Philip W. Friederich ◽  
George P. Vlasuk ◽  
William E. Rote ◽  
Margaretha B. Vroom ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Interleukin 6 ◽  
Recombinant Factor Viia ◽  
Factor Viia ◽  
Human Subjects ◽  
In Vitro Experiments ◽  
Healthy Human ◽  
Healthy Human Subjects ◽  
Proinflammatory Responses

ABSTRACT The activation of coagulation has been shown to contribute to proinflammatory responses in animal and in vitro experiments. Here we report that the activation of coagulation in healthy human subjects by the administration of recombinant factor VIIa also elicits a small but significant increase in the concentrations of interleukin 6 (IL-6) and IL-8 in plasma. This increase was absent when the subjects were pretreated with recombinant nematode anticoagulant protein c2, the inhibitor of tissue factor-factor VIIa.

scholarly journals The effect of marine oil-derived n-3 fatty acids on transepithelial calcium transport in Caco-2 cell models of healthy and inflamed intestines

2007 ◽  
Vol 97 (2) ◽  
pp. 281-288 ◽  
Author(s):  
Jennifer Gilman ◽  
Kevin D. Cashman
Keyword(s):  
Fatty Acids ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Human Subjects ◽  
Healthy Human ◽  
Marine Oil ◽  
Ca Transport ◽  
Tnf Α

Marine oil-derived n-3 fatty acids have been shown to stimulate intestinal Ca absorption in animal studies, but the effects of such fatty acids on Ca absorption in human subjects are relatively unknown. In particular, n-3 fatty acids may be of therapeutic value for some Crohn's disease patients who experience Ca malabsorption. Therefore, the aim of the present study was to investigate the effect of 20 : 5n-3 and 22 : 6n-3 on transepithelial Ca transport across monolayers of healthy Caco-2 cells as well as of TNF-α-treated Caco-2 cells (an in vitro model of Crohn's disease). Caco-2 cells were seeded onto permeable filter supports and allowed to differentiate into monolayers, which were treated with 80 μm-20 : 5n-3, 80 μm-22 : 6n-3, or 40 μm-20 : 5n-3+40 μm-22 : 6n-3 for 6 or 8 d, with or without co-treatment with TNF-α (10 ng/ml) (n 11–15 monolayers per treatment). On day 16, transepithelial and transcellular transport of 45Ca and fluorescein transport (a marker of paracellular diffusion) were measured. Treatment of healthy and inflamed Caco-2 cells with 20 : 5n-3, 22 : 6n-3 and both fatty acids combined for 8 d significantly (P < 0·005–0·01) increased total transepithelial Ca transport compared with that in control, effects which were mediated by an enhanced rate of transcellular Ca transport. The effects of n-3 fatty acids on Ca absorption after 6 d were less clear-cut. In conclusion, the present in vitro findings highlight the need to investigate the effect of marine oil-based n-3 fatty acids on Ca absorption in vivo in studies of healthy human subjects as well as of Crohn's disease patients.

Boosting the Food Functionality (In Vivo and In Vitro) of Spirulina by Gamma Radiation: An Inspiring Approach

2015 ◽  
Vol 11 (4) ◽  
pp. 579-585 ◽  
Author(s):  
Jahid M. M. Islam ◽  
Md. Ismail ◽  
Md. Rakibul Islam ◽  
Md. Faruk Hossain ◽  
Hossain Uddin Shekhar
Keyword(s):  
Radiation Dose ◽  
Gamma Radiation ◽  
Binding Capacity ◽  
Chemical Properties ◽  
Maximum Level ◽  
Biologically Active ◽  
Optimum Dose ◽  
Radiation Doses

Abstract Foods (natural or processed) containing known biologically active compounds, which supplies clinically established and well-documented health benefits, are termed as functional food. Study objectives were to boost food functionality of spirulina, to optimize the required radiation dose, and to test functionality of spirulina both in vitro and in vivo. For this purpose fat binding capacity, sugar binding capacity, hydration property, antioxidative property, total polyphenol content were assessed at different radiation doses. A total of 30 rats were divided into three groups to carry out in vivo experiments to validate the outcomes of in vitro experiments. Targeted physico-chemical properties of spirulina were increased at their maximum level at 15 kGy radiation dose. In vivo experiments validated the outcomes of in vitro experiments. Though gamma radiation improves food functionality of spirulina at various radiation doses, but the optimum dose is recommended as 15 kGy.

scholarly journals Cytochrome P450 Isoforms in the Metabolism of Decursin and Decursinol Angelate from Korean Angelica

2015 ◽  
Vol 43 (06) ◽  
pp. 1211-1230 ◽  
Author(s):  
Jinhui Zhang ◽  
Li Li ◽  
Suni Tang ◽  
Thomas W. Hale ◽  
Chengguo Xing ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Single Dose ◽  
Human Subjects ◽  
Healthy Human ◽  
Decursinol Angelate ◽  
Competitive Inhibitors ◽  
Order Of Magnitude ◽  
Cyp Isoforms ◽  
Insight Into

We have shown that the in vitro hepatic microsomal metabolism of pyranocoumarin compound decursinol angelate (DA) to decursinol (DOH) exclusively requires cytochrome P450 (CYP) enzymes, whereas the conversion of its isomer decursin (D) to DOH can be mediated by CYP and esterase(s). To provide insight into specific isoforms involved, here we show with recombinant human CYP that 2C19 was the most active at metabolizing D and DA in vitro followed by 3A4. With carboxylesterases (CES), D was hydrolyzed by CES2 but not CES1, and DA was resistant to both CES1 and CES2. In human liver microsomal (HLM) preparation, the general CYP inhibitor 1-aminobenzotriazole (ABT) and respective competitive inhibitors for 2C19 and 3A4, (+)-N-3-benzylnirvanol (NBN) and ketoconazole substantially retarded the metabolism of DA and, to a lesser extent, of D. In healthy human subjects from a single-dose pharmacokinetic (PK) study, 2C19 extensive metabolizer genotype (2C19*17 allele) tended to have less plasma DA AUC0-48h and poor metabolizer genotype (2C19*2 allele) tended to have greater DA AUC0-48h. In mice given a single dose of D/DA, pretreatment with ABT boosted the plasma and prostate levels of D and DA by more than an order of magnitude. Taken together, our findings suggest that CYP isoforms 2C19 and 3A4 may play a crucial role in the first pass liver metabolism of DA and, to a lesser extent, that of D in humans. Pharmacogenetics with respect to CYP genotypes and interactions among CYP inhibitor drugs and D/DA should therefore be considered in designing future translation studies of DA and/or D.

Identification and Metabolic Profiling of a Novel Human Gut-derived LEAP2 Fragment

2020 ◽  
Author(s):  
Christoffer A Hagemann ◽  
Chen Zhang ◽  
Henrik H Hansen ◽  
Tina Jorsal ◽  
Kristoffer T G Rigbolt ◽  
...  
Keyword(s):  
Weight Loss ◽  
Gastric Bypass ◽  
Therapeutic Potential ◽  
Metabolic Effects ◽  
Growth Hormone Secretagogue Receptor ◽  
Healthy Human ◽  
Growth Hormone Secretagogue ◽  
Gut Hormone ◽  
Small Intestinal

Abstract Context The mechanisms underlying Roux-en-Y gastric bypass (RYGB) surgery-induced weight loss and the immediate postoperative beneficial metabolic effects associated with the operation remain uncertain. Enteroendocrine cell (EEC) secretory function has been proposed as a key factor in the marked metabolic benefits from RYGB surgery. Objective To identify novel gut-derived peptides with therapeutic potential in obesity and/or diabetes by profiling EEC-specific molecular changes in obese patients following RYGB-induced weight loss. Subjects and Methods Genome-wide expression analysis was performed in isolated human small intestinal EECs obtained from 20 gut-biopsied obese subjects before and after RYGB. Targets of interest were profiled for preclinical and clinical metabolic effects. Results Roux-en-Y gastric bypass consistently increased expression levels of the inverse ghrelin receptor agonist, liver-expressed antimicrobial peptide 2 (LEAP2). A secreted endogenous LEAP2 fragment (LEAP238-47) demonstrated robust insulinotropic properties, stimulating insulin release in human pancreatic islets comparable to the gut hormone glucagon-like peptide-1. LEAP238-47 showed reciprocal effects on growth hormone secretagogue receptor (GHSR) activity, suggesting that the insulinotropic action of the peptide may be directly linked to attenuation of tonic GHSR activity. The fragment was infused in healthy human individuals (n = 10), but no glucoregulatory effect was observed in the chosen dose as compared to placebo. Conclusions Small intestinal LEAP2 expression was upregulated after RYGB. The corresponding circulating LEAP238-47 fragment demonstrated strong insulinotropic action in vitro but failed to elicit glucoregulatory effects in healthy human subjects.

scholarly journals The pharmacokinetics of acyl, des-acyl, and total ghrelin in healthy human subjects

2013 ◽  
Vol 168 (6) ◽  
pp. 821-828 ◽  
Author(s):  
Jenny Tong ◽  
Nimita Dave ◽  
Ganesh M Mugundu ◽  
Harold W Davis ◽  
Bruce D Gaylinn ◽  
...  
Keyword(s):  
Human Subjects ◽  
Dose Range ◽  
Area Under The Curve ◽  
Compartmental Analysis ◽  
Volume Of Distribution ◽  
Metabolic Effects ◽  
Pharmacokinetic Parameters ◽  
Healthy Human ◽  
Gh Secretion ◽  
Total Ghrelin

BackgroundGhrelin stimulates GH secretion and regulates energy and glucose metabolism. The two circulating isoforms, acyl (AG) and des-acyl (DAG) ghrelin, have distinct metabolic effects and are under active investigation for their therapeutic potentials. However, there is only limited data on the pharmacokinetics of AG and DAG.ObjectivesTo evaluate key pharmacokinetic parameters of AG, DAG, and total ghrelin in healthy men and women.MethodsIn study 1, AG (1, 3, and 5 μg/kg per h) was infused over 65 min in 12 healthy (8 F/4 M) subjects in randomized order. In study 2, AG (1 μg/kg per h), DAG (4 μg/kg per h), or both were infused over 210 min in ten healthy individuals (5 F/5 M). Plasma AG and DAG were measured using specific two-site ELISAs (study 1 and 2), and total ghrelin with a commercial RIA (study 1). Pharmacokinetic parameters were estimated by non-compartmental analysis.ResultsAfter the 1, 3, and 5 μg/kg per h doses of AG, there was a dose-dependent increase in the maximum concentration (Cmax) and area under the curve (AUC(0–last)) of AG and total ghrelin. Among the different AG doses, there was no difference in the elimination half-life, systemic clearance (CL), and volume of distribution. DAG had decreased CL relative to AG. The plasma DAG:AG ratio was ∼2:1 during steady-state infusion of AG. Infusion of AG caused an increase in DAG, but DAG administration did not change plasma AG. Ghrelin administration did not affect plasma acylase activity.ConclusionsThe pharmacokinetics of AG and total ghrelin appears to be linear and proportional in the dose range tested. AG and DAG have very distinct metabolic fates in the circulation. There is deacylation of AG in the plasma but no evidence of acylation.

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