1 / 10

PANCREASUL ENDOCRIN

PANCREASUL ENDOCRIN. Mering ; Minkovscki (1898 rolul endocrin al pancreasului-pancreatectomia – diabet zaharat

analu
Download Presentation

PANCREASUL ENDOCRIN

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. PANCREASUL ENDOCRIN Mering; Minkovscki (1898 rolulendocrin al pancreasului-pancreatectomia –diabetzaharat Pancreasulendocrin-insuleleLangerhans-formatiuniovoide 1gr. –coadapancreasului-hormonipolipeptidici: insulina –celule beta, centrulinsulei; glucagon-celulealfaperiferiainsuleisomatostatin-celuledelta;polipeptidul pancreatic-celule F “enterocromafine” !!obtinereahormonilor – distrugerea de catreenzimeleproteoliticesecretiaexocrina INSULINA- PRIMA IZOLARE N.PAULESCU—Best siBanting-extract apos din pancreas –ligatura canal Wirsung –Premiul Nobel 1923. STRUCTURA:Sanger 1957; sintezaKatsoyannis 1964 GM.6000 dalt. 2 lanturipolipeptidice A 21 aa ,B 30 aa unite legaturipuntidisulfidice (distrugereinactivare)

  2. SINTEZA INSULINEI- RETICUL ENDOPLASMATIC-celule beta- mARN - ribozomipreprohormon---proinsulina –lantpolipeptidic A si B polipeptidic C 31aa –ROLUL punelant A si B in pozitiepentrurealizareapuntidisulfidice • Kalicreinatisulara (?? enzimaproteoliticatripsina)—pierdepolipeptid C –Insulinaactiva- aparat Golgi-stocata in granule de secretie-eliberareaprinexocitozacalciudependenta • In sange: insulina, proinsulina( activitate 10%din act. Insulina- NU poatefitrasformata in insulina) ,polipeptidul C (dozareradioimunoprecipitare –indicator al activitatiicelule B –administrare de insulinaexogena) • Pancresaendocrin 200 UI-secretiazilnica 40-60UI-!!!inanitie 10UI/24 h. • 1 unitate de Insulina-cantitatea minima de hormon care trebuieinjectataunuiiepure gr.2kg. Infometat 24h reduce glicemia de la 120mg% la 45mg%-biologic!!! • Captareainsulinei:ficat ,rinichi, muschischeletici. Timpul de injumatatire 5 minute- SECRETIA DE INSULINA CONTINUU

  3. ACTIUNEA INSULINEIHORMON ANABOLIC/ ANTICATABOLIC-METABOLISM-Glucidic, lipidic,protidic • aadm. Intravenoshipoglicemia 30 min ; adm. Subcutanathipoglicemie 2-4h combinare Zn, protamina, globinaresorbtielenta ( protamin zinc insulina –hipoglicemie 18-36h). • RECEPTOR pentruinsulina –suprafatamembranei 2 subunitatialfa- la suprafatamembranei ; 2 beta in membrana-glicoproteice)Nr. variabil --crestereaconcentratieiinsulina in sange –scadenumarreceptori (obezitate, acromegalie) –rezistenta la actiuneainsulinei. • Complex insulina-receptor captat de celula –endocitozamediata de receptor- enzimelizozomaledesprindreceptorii- reciclati-actiuneinsulinainternalizata

  4. EFECTE METABOLICEGlucidic: HIPOGLICEMIE:-crestereapermeabilitatiimembranelorpt.glucoza(difuziunefacilitata)tesut muscular :striat, netedsi cardiac, adipos, tesutconjunctiv, osos, leucocite, nerviiperiferici ,glandemamare, celule A pancreas Neuronii din creier, celule intestinale, celule tubulare renale, eritrocite intrarea glucozei – fara insulina • Glucoza absorbita in intestin- depozitata in ficat- glicogen-glicogenogeneza!!!- inhiba glicogenoliza – stimuleaza sinteza de glicogen • Inhiba fosforilaza +activeaza glucokinaza- fosforilarea glucoza- ( glucozo – 6 fosfat)- difuzeaza in hepatocite) • -stimuleaza enzimelor implicate in sinteza de glicogen: fosfofructokinaza+ glicogen-sintetaza • 5-6% glicogen hepatic—sinteza se sisteaza- glucoza –acizi grasi tesut adipos-depozitare • Fibra muscularain repaus NU intra glucoza fara insulina- acizi grasi sursa de energie-insulina faciliteaza incarcarea G. pe pe transportor- difuziune facilitata • EFFORT FIZIC FARA INSULINA

  5. METABOLISM LIPIDIC • Crestesinteza de acizigrasi in ficat • Ficat- glucoza NU glicogen-- acid piruvic-acetil-CoA- acizigrasi • Acizigrasiformaresi in tesutadipos • Insulina –intrareglucozei in celuleadipoase • Glicoliza in celuleadipoase—alfaglicerolfosfat – glicerol+ acizigrasi = trigliceride • Inhibalipoliza- inhibalipazahormonodependenta

  6. METABOLISM PROTEINE • Anabolizantproteic • Crestereapermeabilitatiipt.aa- stimuleazaactivitatearibozomilor- stimuleazasinteza de proteine • Inhibacatabolismulproteic • Inhibaenzimelerol in gliconeogeneza • inhibamobilizareaaa din ficat,muschi (DZ bilantazotatnegativ-reducereasintezei de proteine- imunoglobuline- scaderearezistentei la infectii) • Electroliti • Insulina- activeaza transport K+,Ca++,fosfat din sange in celule- maresc potential de repaus- activarea ATP-azeiNasi K dependente-!!risc de hipopotasemie—scadesecretia de insulina • INSULINA FACTORULPRINCIPAL DE REGLARE AL GLICEMIEI-APARAT glicoreglator-centriinervosi. HIPOGLICEMIE

  7. REGLAREA SECRETIEI DE INSULINA • Factor principal –GLICEMIA • ConcentratiacAMP in celule beta pancreas, conc. In sange de Ca++ si K+ • Cresterea conc. intracelulare de Ca++- stimuleazasecretia de insulina- exocitozacalciudependenta • Stimulare DIRECTA celule beta pringlicemie-latenta de 30 -60 sec.-depolarizareapartialacelule beta- deschidereacanalelor de Ca voltajdependente- afluxmasiv de Ca din lichid interstitial • Stimulare- aa , arginina,leucina, cetoacizi, corpicetonici • Crestereaconc.intracelularecAMP (glucagon, agenti beta adrenergici,inhibitoriifosfodiesterazei-teofilina) • Simpatic-inhibasecretia de insulinaact.directa • Parasimpatic –vag-stimularesecretie- preprandial , in alimentatie

  8. Reglarea secretia insulina • !!hormoniigastrointestinali-CCK,secretina, enteroglucagon, GIP-stimuleaza direct secretia de insulina !!!adm. Orala de glucoza- crestesecretiainsulina >>> adm. parenterala • !!! HORMONII HIPERGLIGEMIANTI – CRESC SECRETIA DE INSULINA • STH-reduce consumglucoza+ mobilizareacizigrasi • T3-T4- crescabsorbtia de glucoza+ glicogenoliza • ACTH+ glicocorticiozi- stimuleazagluconeogeneza+ reduce captareaglucoza • adrenalina-glicogenoliza hepatica • Glucagon-glicogenoliza hepatica+ stimuleazagluconeogeneza

  9. GLUCAGON POLIPEPTID-29 aa,3500 dalt - desc. Wunsch 1967 HIPERGLICEMIE - Mecanism –cAMP in ficat –stimuleazaglicogenoliza hepatica(!!! NU musculara) • Gluconeogeneza + glicocorticoizi • Ureogeneza(printransformareaaa in glucoza) • Dezaminare hepatica –efectcalorigen • !!!glicogenoliza+ gluconeogeneza= glicemia ==constanta in inanitie • lipolizain tesutadipos • Catabolism-mobilizareaaa , glucozasiac.grasi din depozite • Stimuleazasecretia:insulina, STH, somatostatin,catecolamine • Crestefiorta de contractie a miocard-(inotrop +-; cAMP in f. miocardica ) secretiabiliara • Inhibasecretiagastrica • REGLARE-GLICEMIE- cresteglicemia-- scadesecretia de glucagon. Hiperglicemia – stimuleazasecretia glucagon Direct / indirect SNV simpatic

  10. HOMEOSTAZIA GLICEMIE • A jeun 90-100 mg%. Inanitia- 60-70 mg% ; postprandial ( alimentatie HC ) 120-130 mg% • Surseglucozasanguina: 1. hidratii de carbon din alimentatie- crestereapostprandiala cu25% a glicemie) 2. glicogenoliza hepatica 3.gluconeogeneza(nformarea de “novo” a glucozei din: aminoacizi Glicerol Produsidegradareglucoza: acid lactic, acid piruvic MENTINEREA CONSTANTA A GLICEMIE:FICAT SI TESUTURI EXTRAHEPATICE; SISTEMUL NERVOS; GLANDE ENDOCRINE Ficat : CAPTEAZA, METABOLIZEAZA,STOCARE, ELIBERARE GLUCOZA SN-REACTII DE STRES+ CONTROLUL GLADELOR ENDOCRINE

More Related