Etude des signaux calciques hépatocytaires induits par les agonistes modulateurs de la sécretion biliaire et de la production du glucose (acides biliaires, prostaglandines et glucagon)

LA COMMUNICATION INTERCELLULAIRE JOUE UN ROLE ESSENTIEL DANS LE FONCTIONNEMENT DES ORGANISMES MULTICELLULAIRES. PLUSIEURS BIOMOLECULES SONT CAPABLES DE PROVOQUER DES AUGMENTATIONS DE LA [CA2+]i DANS LES CELLULES STIMULEES. CES AUGMENTATIONS DE LA [CA2+]i CONSTITUENT UN SIGNAL QUI REGULE PLUSIEURS PROCESSUS CELLULAIRES. DES ETUDES ANTERIEURES ONT MONTRE QUE LES AGONISTES COMME LA VASOPRESSINE ET LA NORADRENALINE PROVOQUENT AU SEIN DES DOUBLETS D'HEPATOCYTES DES OSCILLATIONS COORDONNEES DONNANT L'APPARENCE DE VAGUES CALCIQUESINTERCELLULAIRES. LE MODELE PROPOSE POUR EXPLIQUER LA PROPAGATION DES VAGUES CALCIQUES AINSI QUE LA COORDINATION DES OSCILLATIONS CALCIQUES INDUITES PAR CES AGONISTES REPOSE SUR DEUX FACTEURS ESSENTIELS :-LA PERMEABILITE DES JONCTIONS COMMUNICANTES ENIRE HEPAXOCYTES;-LA DIFFUSION DE L'INSP3 A TRAVERS LES JONCTIONS COMMUNICANTES FAVORISEE PAR UN GRADIENT DE PRODUCTION DE L'INSP3. CETTE ORGANISATION SPATIO-TEMPORELLE DU SIGNAL CALCIQUE INDUIT PAR LA NORADRENALINE ET LA VASOPRESSINE SERAIT IMPORTANTE POUR CERTAINES FONCTIONS DU FOIE COMME LA SECRETION BILIAIRE ET LA PRODUCTION HEPATIQUE DE GLUCOSE. DANS CE TRAVAIL, NOUS AVONS ETUDIE LES SIGNAUX CALCIQUES INDUITS PAR DIFFERENTS AGONISTES IMPLIQUES DANS LA PHYSIOLOGIE HEPATIQUE, LES ACIDES BILIAIRES QUI REGULENT LA SECRETION BILIAIRE, LES PROSTAGLANDINES ET LE GLUCAGON QUI ACTIVENT LA PRODUCTION HEPATIQUE DE GLUCOSE. NOS RESULTATS MONTRENT QUE LE MODELE PROPOSE POUR EXPLIQUER LES VAGUES CALCIQUES INIERCELLULAIRES POURRAIT S'APPLIQUER AUX AGONISTES ETUDIES. DE PLUS ILS CONFIRMENT L'IMPORTANCE DES VAGUES CALCIQUES INTERCELLULAIRES POUR LES FONCTIONS DU FOIE.INTERCELLULAR COMMUNICATION PLAYS A CRUCIAL ROLE IN MULTICELLULAR ORGANISM FUNCTIONING. SEVERAL BIOMOLECULES ARE CAPABLE TO INDUCE [CA2+]i INCREASE IN STIMULATED CELLS. THESE [CA2+]i INCREASES CONSTITUTE A SIGNAL WHICH REGULATE SOME CELLULAR PROCESS. PREVIOUS STUDIES HAVE SHOWN THAT THE AGONISTS SUCH AS VASOPRESSIN AND NORADRENALINE PROVOKE IN HEPATOCYTE DOUBLETS COORDINATED OSCILLATIONS WHICH LOOK LIKE INTERCELLULAR CA2+ WAVES. THE MODEL PROPOSED TO EXPLAIN THE SPREAD OF CALCIUM WAVES AND THE COORDINATION OF CA2+ OSCLLLAIIONS INDUCED BY THESE AGONISTS RELIES ON TWO ESSENTIAL CONDITIONS. -THE PERMEABILITY OF COMMUNICATING JUNCTIONS BETWEEN HEPATOCYIE DOUBLETS. -THE INSP3 SPREAD THROUGH COMMUNICATING JUNCTIONS FACILITATED BY THE GRADIENI OF INSP3 PRODUCTION. THE SPATIO-TEMPORAL ORGANISATION OF CA2+ SIGNAL INDUCED BY NORADRENALINE AND VASPRESSIN COULD BE IMPORTANT FOR CERTAIN LIVER FUNCTIONS SUCH AS BILIARY SECRETION AND GLUCOSE OUT PUT. WE HAVE STUDIED CA2+ SIGNALS INDUCED BY DIFFERENTS AGONISTS WHICH ARE IMPLICATED IN HEPATIC PHYSIOLOGY: BILIARY ACIDS WHICH REGULATE BILIARY SECREIION; PROSTAGLANDINS AND GLUCAGONS WHICH ACTIVATED GLUCOSE OUTPUT. OUR RESULTS SHOW THAT THE MODEL WHICH IS PROPOSED TO EXPLAIN THE INTERCELLULAR CA2+ WAVES COULD BE APPLIED TO STUDIED AGONISTS. MORE OVER OUR RESULTS CONFIRM THE IMPORTANCE OF INTERCELLULAR CA2+ WAVES TO LIVER FUNCTIONS.ORSAY-PARIS 11-BU Sciences (914712101) / SudocSudocFranceF

Toxicological and anti-hyperglycemic studies of five plants used for the treatment of type 2 diabetes in Benin

In Benin as in the African sub-region, the burden of Non-Communicable Diseases (NCDs) and the threats they represent constitute a major public health problem which hinders their economic and social development. NCDs kill 36 million people each year and 80% of deaths occur in developing countries, including Benin. The objective of our work is to evaluate the acute, subacute toxicity and the anti-hyperglycemic activity of five plants listed through an ethno pharmacological survey which is used for the treatment of type 2 diabetes in Benin. The acute toxicity test was conducted on male and female wistar rats at a single dose of 2000 mg/kg. The subacute toxicity test was carried out over a period of 28 days, with 6 batches of 3 rats. Batch 1 received daily 1 ml/100 g of distilled water and batches 2, 3, 4 and 5 respectively the leaf extracts of Bambusa vulgaris Schrad. Ex-Wendel; Parkia biglobosa (Jacq.) R. Br. Ex G. Don; Mangifera indica L.; Saccharum officinarum L.; And Annona muricata L. at a daily dose of 200mg/kg per day for 28 days. Administration of the single dose of the extract did not cause any deaths. In rats treated with repeated doses of 200mg/kg for 28 days the variation in weight depends on the extracts. The level of transaminases (AST and ALT) did not vary. Plant extracts did not induce any significant change in creatinine level. All five extracts have anti-hyperglycemic activity. Our results allow us to deduce that these plants can be used to prevent and treat diabetes without the risk of hepatic and renal toxicity. Keywords: Medicinal plants; Type 2 diabetes; Toxicity; efficac