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MecanismulMecanismul fiziopatologicfiziopatologic alal diabetuluidiabetuluizaharatzaharat

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ExistaExista douadoua formeforme dede diabetdiabet

Diabet de tip 1 - insulino-dependent

Incidenta:

1: 600 in US si Europa

1:10000 in Asia de Est

Diabet de tip 2- insulino-non-dependent.

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InsulinaInsulina esteeste produsulprodusul dede

secretiesecretie alal celulelorcelulelor

(1869 - 1931)

Pancreasul contine intre 500.000 si cateva milioane de insule Langerhans.

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CeCe faceface insulinainsulina????

Act ioneaza pe ficat, m uschi si t esut adipos unde CREAZACREAZA REZERVE DEREZERVE DE

ENERGIEENERGI E..

I n inanit ie: Secret ia de insuli na scade.

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GlicemiaGlicemia variazavariaza inin timpultimpul zileizilei, in, in functiefunctie dede locullocul

dede recoltarerecoltare sausau stareastarea dede nutritienutritie

>7,5%6,2-7,5%Hemoglobina glicozilata

(HbA1c)

>139 mg/dl (>7,7 mmol/l)

>200 mg/dl (>11,1 mmol/l)

110-139 mg/dl (6-7,7 mmol/l)

140-200 mg/dl (7,8-11,1mmol/l)

Glicemie plasmatica (inlaborator, din vena)

- Pe nemancate- La 2 ore dupa masa

>120 mg/dl (>6,5 mmol/l)

>160 mg/dl (>9 mmol/l)>135 mg/dl (>7,5 mmol/l)

91-120 mg/dl (5,1-6,5 mmol/l)

136-160 mg/dl (7,6-9 mmol/l)110-135 mg/dl (6-7,5 mmol/l)

Glicemie capilara (pe test,

din deget)- Pe nemancate

- La 2 ore dupa masa- La culcare

Nivel neadecvatNivel adecvatParametrii

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GlucozaGlucoza esteeste reglatorulreglatorul celcel maimai important alimportant al secretieisecretiei

dede insulinainsulina

Dimineata, dupa o noapt e de nemancare, glicemia este in j ur de 90-100

mg/ dl. Ea creste dupa masa, dar nu depaseste in mod normal 200 mg/ dl .

Diabetul se instaleaza la valor i de peste 360 mg/ dl glucoza.

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GlucozaGlucoza administrataadministrata intravenosintravenos determinadetermina maimai rapid orapid o

cresterecrestere aa secretieisecretiei dede insulinainsulina

Insulina deja sintetizata si

inmagazinata in veziculele

din celulele beta; 2-5 min

Insulina deja sintetizata +

nou sintetizata

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SecretiaSecretia dede insulinainsulina

esteeste initiatainitiata dede

metabolizareametabolizarea

glucozeiglucozei,, galactozeigalactozei sisi

manozeimanozei dede catrecatrecelulelecelulele

isoproterenol noradrenalina

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InsulinaInsulina actioneazaactioneaza asupraasupra unorunor receptorireceptori specificispecifici dindin

membranamembrana tesuturilortesuturilor tintatinta care aucare au domeniidomenii tirozintirozin--kinazicekinazice

Insulina

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LegareaLegarea

insulineiinsulinei pepe

tesuturiletesuturiletintatinta are caare ca

efectefect

crestereacresterea

depozitariidepozitarii sisi

folosiriifolosirii

glucozeiglucozei,,

crestereacresterea

sintezeisintezei

proteiceproteice sisi aa

TG,TG,

stimulareastimulareaexpresieiexpresiei

genicegenice sisi

dezvoltareadezvoltarea

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InIn diabetuldiabetul de tip Ide tip I sausau diabetuldiabetul juveniljuvenil,, insulinainsulina

lipsestelipseste completcomplet

Enterovirusuri familia Cocksakie B

HLA-DR3 si HLA-DR4

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Tsui et al, 200 3

InIn juruljurul insulelorinsulelor LangerhansLangerhans existaexista oo teacateaca dede

celulecelule SchwannSchwann

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Tsui et al, 2007 , Trends Mol Med

care lecare le poatepoate protejaproteja impotrivaimpotriva unuiunui atacatac

autoimunautoimun

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InIn diabetuldiabetul de tip IIde tip II sausau diabetuldiabetul maturmatur,, secretiasecretia dede

insulinainsulina poatepoate fifi normalanormala sausau chiarchiar crescutacrescuta,, dardar

organeleorganele tintatinta raspundraspund slab laslab la insulinainsulina

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NiveleleNivelele ridicateridicate dede insulinainsulina determinadetermina oo exprimareexprimare

redusaredusa aa receptorilorreceptorilor pentrupentru insulinainsulina

Celulele expuse cronic la concent rat ii mari de insulina au mai put in receptor i

decat cele expuse la concentrati i mai m ici, manifestand fenomenul de rezist entala insulina .

Efectele diabetu lui de

t ip 2 NU suntdeterminat e de

scaderea numarulu i dereceptori, ci de

alterarea cascadelor

intracelulare de dupa

legarea insulin ei dereceptor

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TesutulTesutul adiposadipos inin excesexces esteeste cauzacauza principalaprincipala aa

diabetuluidiabetului de tip 2de tip 2

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DiabetulDiabetul de tip IIde tip II poatepoate fifi determinatdeterminat sisi dede altealte

cauzecauze

Hormoni antagonisti: somatotropina in acromegalie glucocorticoizii in sindrom ul Cushing

adrenalina in str ess progesteronul si gonadotr opina corionica insarcina

ACTH hormonii tiroidieni

glucagonul

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HipotalamusulHipotalamusul

controleazacontroleaza

aportulaportul dedealimentealimente prinprin

centrulcentrul foameifoamei

sisi alal satietatiisatietatii

Centrul satiet atii

Centrul foamei

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carecare suntsunt

influentatiinfluentati dede

oo serieserie dede

mediatorimediatoriorexigeniciorexigenici

sausau

anorexigenicianorexigenici

factorii pe termen scurt - reflecta aportul de alimente)factorii pe termen lung- reflecta depozitele de energie

ale organismului

GLP- glucagon-like peptide

EOP- endogenou s opioid pept ide

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InformatiileInformatiile despredespre rezervelerezervele energeticeenergetice,, aportulaportul dede

alimentealimente sisi necesitatilenecesitatile metabolicemetabolice suntsunt procesateprocesate dede

nucleulnucleul arcuatarcuat

Nc. Arcuat mai controleaza ritmul circadian,activit atea sexuala, raspunsurile emot ionale

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POMC- pro-opiomelanocortinCART- cocaine & amphetamine regulated transcriptAgrp- agouti related protein (agouti= un hormon cedetermin a pigmentarea blanii la Augoutis (rozatoare)

NPY- neuropept ide Y

The orexigenic message of ghrelin enters the

brain via the vagus nerve and causes local

release of ghrelin from ghrelin-containing

neurons. Ghrelin binds to its receptor on

Npy/AgRP/GABA neurons, giving rise to an

increased production of Npy and AgRP aswell as an increased firing rate of these

neurons. The consequences are twofold:

firstly, inhibition of firing of POMC/CART

neurons (through GABA) and secondly

stimulation of firing of the orexigenic neurons

in the LHA/PFA region (through Npy and

AgRP). A predominant orexigenic signal

ensues.

Insulin and leptin directly diffuse into the

arcuate nucleus and they bind to theirreceptors on both Npy/AgRP/GABA and

POMC/CART neurons. However, they have

opposing effects on these neurons. Leptin and

insulin promote expression of -MSH

(anorexigenic) but suppress expression of Npy

and AgRP (orexigenic). As a consequence a

predominant anorexigenic signal ensues.

Messenger abbreviations: Npy, neuropeptide

Y, AgRP, agouti-related protein, GABA,

gamma-amino butyric acid; -MSH, alpha-

melanocyte stimulating

hormone=melanocortin

Receptor abbreviations: GSHR, growth

hormone-secretagogue receptor=ghrelin

receptor; LepR, leptin receptor; INSR, insulin

receptor; Y1R, Npy receptor, MC4R,

melanocortin-4 ( -MSH) receptor.

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ConsumulConsumul dede siropsirop concentratconcentrat dede fructozafructoza contribuiecontribuie

lala aparitiaaparitia obezitatiiobezitatii

Basciano, 20 05

Consumul de nut rienti cu indexglicemic cazut cum sunt fructozasi grasimile induce satietate mai

incet si deci determina un aportde alimente mai mare.

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One for the Ages: A Prescription That May Extend Life

Octombr ie, 2006

http://www.nytimes.com/2006/10/31/health/nutrition/31agin.html