20 research outputs found
Cellules stromales prostatiques en culture (étude des composantes statique et dynamique de l'hyperplasie bénigne de la prostate )
L'Hyperplasie BĂ©nigne de la Prostate se caractĂ©rise par deux composantes, dynamique et statique, entraĂźnant des symptĂŽmes obstructifs.La composante dynamique est due Ă la contraction des cellules musculaires lisses, gouvernĂ©e par le rĂ©cepteur alpha1A-adrĂ©nergique (A1A-AR). Afin d'Ă©tudier leurs modalitĂ©s de contraction, nous avons mis au point un nouveau modĂšle de cellules stromales prostatiques de lapin en culture. Ces cellules, maintenues en diffĂ©renciation, conservent l'expression des protĂ©ines du cytosquelette contractile et du A1A-AR. Ce dernier conserve son couplage avec la voie des MAPK et avec celle du calcium.La composante statique est due Ă une prolifĂ©ration cellulaire non tumorale entraĂźnant une augmentation de volume de la glande. Sur un modĂšle de cellules stromales humaines en culture, nous avons montrĂ© que l'extrait de plante Pygeum africanum inhibe la prolifĂ©ration cellulaire induite par du sĂ©rum de veau fĆtal, du bFGF et de l'EGF, et ce sans effet de cytotoxicitĂ© aiguĂ«.MONTPELLIER-BU Pharmacie (341722105) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF
OF PHARMACOLOGY w EXPERIMENTAL ThERAPEUTICS Pharmacological Coupling and Functional Role for the Muscarinic Receptor Subtypes in Isolated Cells from the Circular Smooth Muscle of the Rabbit Cecum1
MAP Kinase cross talks in oxidative stress-induced impairment of insulin secretion. Involvement in the protective activity of quercetin
International audienceInsulin secretion preservation is a major issue for the prevention or treatment of type 2 diabetes. We previously showed on ÎČ-cells that quercetin (Q), but not resveratrol (R) or N-acetyl cysteine (NAC), amplified glucose-induced insulin secretion in a calcium- and ERK1/2-dependent manner. Quercetin, but not resveratrol or NAC, also protected ÎČ-cell function and hyperamplified ERK1/2 phosphorylation in oxidative stress conditions. As quercetin may interfere with other stress-activated protein kinases (JNK and p38 MAPK), we further explored MAPK cross talks and their relationships with the mechanism of the protective effect of quercetin against oxidative stress. In INS-1 insulin-secreting ÎČ-cells, using pharmacological inhibitors of MAPK pathways, we found that under oxidative stress (50 ÎŒm H2O2) and glucose-stimulating insulin secretion conditions: (i) p38 MAPK phosphorylation was increased and regulated by ERK1/2 (positively) and JNK (negatively), although p38 MAPK activation did not seem to play any significant role in oxidative stress-induced insulin secretion impairment; (ii) the JNK pathway appeared to inhibit both ERK1/2 activation and insulin secretion, although JNK phosphorylation was not significantly changed in our experimental conditions; (iii) the functionality of ÎČ-cell in the presence of oxidative stress was closely linked to the level of ERK1/2 activation, (iv) quercetin, resveratrol, or NAC inhibited H2O2 -induced p38 MAPK phosphorylation. The preservation of ÎČ-cell function against oxidative stress appears dependent on the balance between ERK1/2 and JNK activation. The protecting effect of quercetin appears due to ERK1/2 hyperactivation, possibly induced by L-type calcium channel opening as we recently showed
COMPOSITIONS COMPRISING UROLITHINS AND USES THEREOF FOR THE STIMULATION OF INSULIN SECRETION
The present invention relates to a composition comprising urolithin A, urolithin B, urolithin C, urolithin D, or a combination thereof, for the stimulation of insulin secretion, and to the use of a compound chosen among urolithin A, urolithin B, urolithin C, urolithin D, or a combination thereof, intended for the stimulation of insulin secretion. The present invention also relates to a composition comprising an effective amount of urolithin B, urolithin C, urolithin D, or a combination thereof, for the treatment or the prevention of diabetes mellitus, and in particular for the treatment or the prevention of type 2 diabetes, and to the use of a compound chosen among urolithin B, urolithin C, urolithin D, and a combination thereof, intended for the treatment or the prevention of diabetes mellitus, and in particular of type 2 diabetes
Effect of glicentin, oxyntomodulin and related peptides on isolated gastric smooth muscle cells
International audienc
Lâacide chicorique est une molĂ©cule antioxydante stimulant la voie AMP Kinase, lâexpression de PGC1 α et lâactivitĂ© mitochondriale dans un modĂšle de cellules musculaires striĂ©es
Poster prĂ©sentĂ© Ă la rĂ©union scientifique de la SFD, de la SFD ParamĂ©dical et de l'AJD, 26-29/03/2013Introduction : Les antioxydants dâorigine alimentaire pourraient prĂ©venir la rĂ©sistance Ă lâinsuline ainsi que le dĂ©veloppement du stress oxydant associĂ© aux maladies mĂ©taboliques. Parmi ceux-ci, les polyphĂ©nols tels que lâacide cafĂ©ique et ses dĂ©rivĂ©s (acide chlorogĂ©nique et acide chicorique) possĂ©deraient des propriĂ©tĂ©s antidiabĂ©tiques. Nous avons Ă©tudiĂ©, sur la lignĂ©e de myoblastes L6, lâinfluence de lâacide chicorique (AC) sur le stress oxydant, lâactivitĂ© mitochondriale, la voie de lâAMPK (protĂ©ine kinase activĂ©e par lâAMP) et celle de lâinsuline.MatĂ©riels et mĂ©thodes: Lâexpression des protĂ©ines et des ARNm a Ă©tĂ© dĂ©terminĂ©e par Western Blot et qPCR. Les espĂšces rĂ©actives de lâoxygĂšne (ROS) ont Ă©tĂ© quantifiĂ©es avec la sonde 2â,7-dichlorofluoresceine. La captation cellulaire de glucose a Ă©tĂ© mesurĂ©e par lâincorporation de 2-deoxy-D-glucose[3H].RĂ©sultats : Dans les myotubes L6, lâAC est un piĂ©geur de ROS en condition basale et en condition de stress oxydant. LâAC augmente lâactivitĂ© des systĂšmes de dĂ©fenses enzymatiques anti-oxydantes glutathion peroxydase et superoxyde dismutase (SOD). Il protĂšge la mitochondrie contre les dommages oxydatifs en augmentant lâexpression de la MnSOD. LâAC augmente lâactivitĂ© du complexe II ainsi que lâexpression de PGC-1α impliquĂ© dans la rĂ©gulation de lâexpression des enzymes anti-oxydantes et la biogĂ©nĂšse mitochondriales. LâAC stimule la voie AMPK/ACC et inhibe la voie Akt/mTOR en prĂ©sence dâinsuline, sans modification de la captation de glucose.Conclusion : LâAC possĂšde des propriĂ©tĂ©s anti-oxydantes, Ă la fois par sa capacitĂ© Ă neutraliser les ROS et Ă augmenter les systĂšmes enzymatiques de dĂ©fense anti-oxydante. LâAC stimule Ă©galement la biogĂ©nĂšse mitochondriale et protĂšge les mitochondries contre les dommages oxydatifs, tout en amĂ©liorant leur capacitĂ© Ă oxyder les acides gras en stimulant lâAMPK et en augmentant lâactivitĂ© du complexe II. Ces rĂ©sultats suggĂšrent que le potentiel de lâacide chicorique Ă prĂ©venir ou traiter les pathologies associĂ©es au syndrome mĂ©tabolique mĂ©rite dâĂȘtre Ă©tudiĂ© de façon plus approfondie
A Total Red Wine Polyphenolic Extract Prevents a Pathological Phenotype Manifested on Cardiomyocytes Isolated from Rats with Nutritionally-induced Metabolic Syndrome
International audienceIsolated cardiomyocyte contractility was explored in a model of metabolic syndrome (the fructose-fed rat) and the effect of a treatment by a total red wine polyphenolic extract (RWPE) determined. Fructose-enriched diet impaired cardiomyocyte maximal shortening and velocities of contraction and relaxation, while RWPE was able to prevent those changes. Those studies suggest that red wine polyphenols are able to prevent the development of a cardiac phenotype commonly observed at an early stage of heart failure
Short-term intravenous insulin infusion is associated with reduced expression of NADPH oxidase p47 phox subunit in monocytes from type 2 diabetes patients
International audienceHyperglycemia is a well-known inducing factor of oxidative stress through activation of NADPH oxidase. In addition to its plasma glucose lowering effect, insulin may also have antioxidant activity and was shown to downregulate NADPH oxidase expression in vitro. In this study, we show that a short-term (3-day) intravenous insulin infusion in patients with type 2 diabetes induces normalization of both glycemia and mRNA expression of circulating monocyte p47(phox) subunit
Quercetin induces insulin secretion by direct activation of L-type calcium channels in pancreatic beta cells
International audienceBackground and Purpose: Quercetin is a natural polyphenolic flavonoid that displays antiâdiabetic properties in vivo. Its mechanism of action on insulinâsecreting beta cells is poorly documented. In this work, we have analysed the effects of quercetin both on insulin secretion and on the intracellular calcium concentration ([Ca2+]i) in beta cells, in the absence of any coâstimulating factor.Experimental Approach: Experiments were performed on both INSâ1 cell line and rat isolated pancreatic islets. Insulin release was quantified by the homogeneous timeâresolved fluorescence method. Variations in [Ca2+]i were measured using the ratiometric fluorescent Ca2+ indicator Furaâ2. Ca2+ channel currents were recorded with the wholeâcell patchâclamp technique.Key Results: Quercetin concentrationâdependently increased insulin secretion and elevated [Ca2+]i. These effects were not modified by the SERCA inhibitor thapsigargin (1âÎŒmol·Lâ1), but were nearly abolished by the Lâtype Ca2+ channel antagonist nifedipine (1âÎŒmol·Lâ1). Similar to the Lâtype Ca2+ channel agonist Bay K 8644, quercetin enhanced the Lâtype Ca2+ current by shifting its voltageâdependent activation towards negative potentials, leading to the increase in [Ca2+]i and insulin secretion. The effects of quercetin were not inhibited in the presence of a maximally active concentration of Bay K 8644 (1âÎŒmol·Lâ1), with the two drugs having cumulative effects on [Ca2+]i.Conclusions and Implications: Taken together, our results show that quercetin stimulates insulin secretion by increasing Ca2+ influx through an interaction with Lâtype Ca2+ channels at a site different from that of Bay K 8644. These data contribute to a better understanding of quercetin's mechanism of action on insulin secretion
Chicoric acid is an antioxidant molecule that stimulates AMP kinase pathway in L6 myotubes and extends lifespan in Caenorhabditis elegans.
Chicoric acid (CA) is a caffeoyl derivative previously described as having potential anti-diabetic properties. As similarities in cellular mechanism similarities between diabetes and aging have been shown, we explored on L6 myotubes the effect of CA on the modulation of intracellular pathways involved in diabetes and aging. We also determined its influence on lifespan of Caenorhabditis elegans worm (C. elegans). In L6 myotubes, CA was a potent reactive oxygen species (ROS) scavenger, reducing ROS accumulation under basal as well as oxidative stress conditions. CA also stimulated the AMP-activated kinase (AMPK) pathway and displayed various features associated with AMPK activation: CA (a) enhanced oxidative enzymatic defences through increase in glutathion peroxidase (GPx) and superoxide dismutase (SOD) activities, (b) favoured mitochondria protection against oxidative damage through up-regulation of MnSOD protein expression, (c) increased mitochondrial biogenesis as suggested by increases in complex II and citrate synthase activities, along with up-regulation of PGC-1α mRNA expression and (d) inhibited the insulin/Akt/mTOR pathway. As AMPK stimulators (e.g. the anti-diabetic agent meformin or polyphenols such as epigallocatechingallate or quercetin) were shown to extend lifespan in C. elegans, we also determined the effect of CA on the same model. A concentration-dependant lifespan extension was observed with CA (5-100 ΌM). These data indicate that CA is a potent antioxidant compound activating the AMPK pathway in L6 myotubes. Similarly to other AMPK stimulators, CA is able to extend C. elegans lifespan, an effect measurable even at the micromolar range. Future studies will explore CA molecular targets and give new insights about its possible effects on metabolic and aging-related diseases