RESUMO
There is evidence that oat ß-glucan lowers appetite and ad libitum eating; however, not all studies are consistent, and the underpinning mechanisms are not entirely understood. We investigated the effects of 4â¯g high molecular weight (MW) oat ß-glucan on ad libitum eating, subjective appetite, glycemia, insulinemia and plasma GLP-1 responses in 33 normal-weight subjects (22 female/11 male, mean age (y): 26.9⯱â¯1.0, BMI (kg/m2): 23.5⯱â¯0.4). The study followed a randomised double-blind, cross-over design with subjects fed two test breakfasts with and without oat ß-glucan followed by an ad libitum test meal on two different days. Blood samples and ratings for subjective appetite were collected postprandially at regular time intervals. Oat ß-glucan increased feelings of fullness (pâ¯=â¯0.048) and satiety (pâ¯=â¯0.034), but did not affect energy and amount eaten at the ad libitum test meal. There was a treatment by time interaction for plasma GLP-1, plasma insulin and blood glucose. GLP-1 was significantly reduced at 90â¯min (pâ¯=â¯0.021), blood glucose at 30â¯min (pâ¯=â¯0.008) and plasma insulin at 30 and 60â¯min (pâ¯=â¯0.002 and 0.017, respectively) following the oat ß-glucan breakfast when compared with the control breakfast. Four grams of high MW oat ß-glucan lowers appetite but not ad libitum eating and beneficially modulates postprandial glycaemia, it does however, not increase plasma GLP-1 secretion.
Assuntos
Apetite/efeitos dos fármacos , Avena , Desjejum/fisiologia , Ingestão de Alimentos/efeitos dos fármacos , beta-Glucanas/administração & dosagem , Adulto , Glicemia/metabolismo , Estudos Cross-Over , Método Duplo-Cego , Feminino , Peptídeo 1 Semelhante ao Glucagon/sangue , Voluntários Saudáveis , Humanos , Insulina/sangue , Masculino , Período Pós-Prandial , Saciação/efeitos dos fármacosRESUMO
BACKGROUND: Infusion of Mg for therapeutic purposes is still a matter for debate. Dosages vary considerably, yet subclinical effects on normal physiology are largely ignored. In human and animal models, interactions between Mg and insulin exist, thus we have investigated the effect of infusing Mg on serum insulin, ionised Mg (Mg(2+)) and Ca (Ca(2+)) and plasma glucose in human volunteers. METHODS: Six male volunteers were infused with magnesium sulphate (MgSO(4)) dissolved in normal saline, using a high-dose "loading" bolus, followed by a lower-level "maintenance" period. FINDINGS: Serum Mg(2+) rose rapidly throughout the bolus infusion, declined during the maintenance phase, but remained higher than pre-infusion levels throughout the experimental period; serum Ca(2+) rose when serum Mg(2+) was highest. Infusion of MgSO(4) had no effect on heart rate or blood pressure, but caused a rapid, pronounced drop in circulating fasting insulin (p<0.0005), which slowly recovered to basal values during the course of the maintenance infusion. A slight, transient rise in plasma glucose (p<0.05) concomitant with the decline in serum insulin was also observed. INTERPRETATION: It is possible that the effect of Mg(2+) on insulin may have been due to antagonism of Ca(2+) entry in pancreatic beta-cells, the insulin decline causing a subsequent rise in circulating glucose levels. We suggest that these effects of MgSO(4) infusions should be considered where the aim is to achieve high doses of blood Mg(2+) levels by clinical intervention.
Assuntos
Insulina/sangue , Magnésio/administração & dosagem , Adulto , Glicemia/análise , Glicemia/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Cálcio/sangue , Regulação para Baixo/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Humanos , Bombas de Infusão , Sulfato de Magnésio/administração & dosagem , Masculino , Projetos Piloto , Fatores de TempoRESUMO
Changes in the regulation of potassium channels are increasingly implicated in the altered activity of breast cancer cells. Increased or reduced expression of a number of K(+) channels have been identified in numerous breast cancer cell lines and cancerous tissue biopsy samples, compared to normal tissue, and are associated with tumor formation and spread, enhanced levels of proliferation, and resistance to apoptotic stimuli. Through knockout or silencing of K(+) channel genes, and use of specific or more broad pharmacologic K(+) channel blockers, the growth of numerous cell lines, including breast cancer cells, has been modified. In this manner it has been proposed that in MCF7 breast cancer cells proliferation appears to be regulated by the activity of a number of K(+) channels, including the Ca(2+) activated K(+) channels, and the voltage-gated K(+) channels hEAG and K(v)1.1. The effect of phytoestrogens on K(+) channels has not been extensively studied but yields some interesting results. In a number of cell lines the phytoestrogen genistein inhibits K(+) current through several channels including K(v)1.3 and hERG. Where it has been used, structurally similar daidzein has little or no effect on K(+) channel activity. Since many K(+) channels have roles in proliferation and apoptosis in breast cancer cells, the impact of K(+) channel regulation by phytoestrogens is of potentially great relevance.
Assuntos
Neoplasias da Mama/metabolismo , Fitoestrógenos/farmacologia , Canais de Potássio/efeitos dos fármacos , Linhagem Celular Tumoral , Feminino , Genisteína/farmacologia , Humanos , Isoflavonas/farmacologia , Canais de Potássio/metabolismoRESUMO
The properties and regulation of volume-activated taurine efflux from MDA-MB-231 and MCF-7 cells have been investigated. Volume-activated taurine release from both cell lines was almost completely inhibited by diidosalicylate. DIDS , was more effective at inhibiting swelling-induced taurine release from MCF-7 than from MDA-MB-231 cells. On the basis of comparing taurine, Cl(-) and I(-) efflux time courses, it appears that volume-activated taurine efflux does not utilize volume-sensitive anion channels in MDA-MB- 231 and MCF-7 cells. Extracellular ATP stimulated volume-activated taurine release from MDA-MB-231 cells but not from MCF-7 cells. The effect of ATP was mimicked by UTP and was dependent upon external calcium and inhibited by suramin. However, suramin inhibited volume-activated taurine efflux from both MDA-MB-231 and MCF-7 cells even in the absence of exogenously added ATP suggesting that it acts directly on the taurine efflux pathway and/or is inhibiting the effect of ATP released from the cells. Volume-activated taurine efflux from MDA-MB-231 cells was stimulated by ionomycin. In contrast, ionomycin had no effect on taurine release from MCF-7 cells. Adenosine also stimulated volume-activated taurine efflux from MDA-MB-231 cells. The results suggest that purines regulate taurine transport in MDA-MB- 231 cells via more than one type of receptor.
Assuntos
Trifosfato de Adenosina/farmacologia , Cloretos/metabolismo , Taurina/metabolismo , Ácido 4,4'-Di-Isotiocianoestilbeno-2,2'-Dissulfônico/farmacologia , Adenosina/farmacologia , Trifosfato de Adenosina/metabolismo , Transporte Biológico/efeitos dos fármacos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Canais de Cloreto/efeitos dos fármacos , Canais de Cloreto/metabolismo , Relação Dose-Resposta a Droga , Feminino , Humanos , Iodetos/metabolismo , Ionomicina/farmacologia , Concentração Osmolar , Suramina/farmacologia , Fatores de TempoRESUMO
We have reported previously that mutation of two conserved nonbasic amino acids (G203 and Q209) within the highly basic 201-218 region in the C-terminal domain of IGF-binding protein-5 (IGFBP-5) decreases binding to IGFs. This study reveals that cumulative mutagenesis of the 10 basic residues in this region, to create the C-Term series of mutants, ultimately results in a 15-fold decrease in the affinity for IGF-I and a major loss in heparin binding. We examined the ability of mutants to inhibit IGF-mediated survival of MCF-7 cells and were able to demonstrate that this depended not only upon the affinity for IGF-I, but also the kinetics of this interaction, because IGFBP-5 mutants with similar affinity constants (K(D)) values, but with different association (Ka) and dissociation (Kd) rate values, had markedly different inhibitory properties. In contrast, the affinity for IGF-I provided no predictive value in terms of the ability of these mutants to enhance IGF action when bound to the substratum. Instead, these C-Term mutants appeared to enhance the actions of IGF-I by a combination of increased dissociation of IGF-IGFBP complexes from the substratum, together with dissociation of IGF-I from IGFBP-5 bound to the substratum. These effects of the IGFBPs were dependent upon binding to IGF-I, because a non-IGF binding mutant (N-Term) was unable to inhibit or enhance the actions of IGF-I. These results emphasize the importance of the kinetics of association/dissociation in determining the enhancing or inhibiting effects of IGFBP-5 and demonstrate the ability to generate an IGFBP-5 mutant with exclusively IGF-enhancing activity.
Assuntos
Proteína 5 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Fator de Crescimento Insulin-Like I/metabolismo , Animais , Sítios de Ligação , Técnicas Biossensoriais , Dicroísmo Circular , Primers do DNA , Proteína 5 de Ligação a Fator de Crescimento Semelhante à Insulina/química , Proteína 5 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Cinética , Mutagênese Sítio-Dirigida , Ratos , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismoRESUMO
The response of isolated preparations of bovine mammary artery was investigated, with the aim of characterising further the adrenergic receptor subtypes present. Noradrenaline (NA) and the alpha(1) agonist phenylephrine gave sigmoidal dose-response curves with pEC(50) values of 5.97+/-0.07 (N=34) and 6.21+/-0.32 (N=8), respectively. Stimulation of alpha(2) receptors with UK 14,304 produced a weak response with pEC(50) of 6.78+/-0.38 (N=7), and maximal contraction of 17.8+/-9.9% relative to NA. A61603, an alpha(1A) agonist, gave a curve parallel to NA, but shifted to the left (pEC(50) of 6.98+/-0.19 (N=5)); this drug had an increased potency of 10-fold relative to NA, and 4-fold relative to phenylephrine. Schild analysis of curves obtained with the alpha(1) antagonist prazosin gave a pA(2) of 8.70+/-0.47 (N=6-9), whereas the alpha(2) antagonist yohimbine resulted in a pA(2) of 7.65+/-0.16 (N=4). The alpha(1A) receptor antagonists WB4101 and 5-methylurapidil gave pA(2) values of 9.39+/-0.69 (N=4) and 7.72+/-0.02 (N=2-3), respectively. The irreversible alpha(1B) inhibitor CEC reduced the pEC(50) from 5.39+/-0.12 to 4.31+/-0.18 (N=7) only at the highest dose used, and high doses of the alpha(1D) antagonist BMY 7378 produced a shift to the right at giving a pA(2) of 7.37+/-0.08 (N=3). These results suggest major involvement of the alpha(1B) adrenergic receptor subtype in contraction of the bovine mammary artery, which is similar to the human internal mammary artery.