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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
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