TRNG I HC S PHM H NI 2 PHNG SAU I HC ---------@--------

BI TIU LUN

TH TH INSULIN V MI QUAN H CA N VI BNH TIU NG

PHM TH THU PHNG LP K14 - SINH HC THC NGHIM

H Ni, 11-2011

MC LC Phn m u Chng 1: Gii thiu v Insulin

1.1 Cu trc phn t Insulin 1.2 Vai tr sinh hc ca Insulin 1.2.1 Tc dng ca Insulin ln qu trnh chuyn ha Hydratcacbon 1.2.2 Tc dng ca Insulin ln qu trnh chuyn ha lipid 1.2.3 Tc dng ca Insulin ln qu trnh chuyn ha protein 1.2.4 Cc tc ng ng ch khc ca Insulin 1.3 Tng hp Insulin trong c th 1.4 iu ha tng hp Insulin Chng 2: Gii thiu v bnh tiu ng 2.1 Dch t hc 2.2 Phn loi, nguyn nhn, triu chng v hng iu tr 2.2.1 Tiu ng typ I 2.2.2 Tiu ng typ II 2.3. Bin chng 2.3.1 Bin chng mt 2.3.2 Bin chng thn 2.3.3 Bin chng tim v mch mu 2.3.4 Bin chng acid ha v tng p lc phn t trong mu (Ketoacidosis and Hyperosmolarity) 2.3.5 Bin chng ca thn kinh 2.3.6 Nhng bin chng da v nhim trng 2.3.7 Nhng bin chng khc Chng 3: Th th Insulin v mi quan h ca n vi bnh tiu ng

3.1 Th th Insulin 3.1.1 Cu trc 3.1.2 Hot tnh tyrosine kinase 3.2 iu ho lng ng trong mu 3.2.1 iu ho phn gii glycogen 3.2.2 S iu ho tng hp glycogen 3.3 Insulin v cc protein vn chuyn glucose Phn kt lun Ti liu tham kho

M U
Bnh tiu ng l mt trong nhng cn bnh e da nghim trng ti sc kho ca con ngi. S ngi mc bnh tiu ng ang ngy cng tng, v ng nhin, s ko theo s gia tng cc bin chng ca cn bnh ny nh thn kinh, x va ng mch Ngi ta tng kt v thy rng tiu ng l nguyn nhn gy t vong ln th 2 trn th gii (sau cc bnh v tim mch). iu i hi phi tm ra nhng hng tip cn mi cho vic ngn nga v iu tr cn bnh ny. Nguyn nhn gy ra bnh tiu ng l do tc ng phc tp gia gene v cc yu t mi trng, t dn ti s bt bnh thng trong qu trnh iu ho lng glucose trong c th lin quan ti nhng vn v hormone Insulin, y la hormone quan trong nht cho qua trinh lu tr, s dung ng, acid amin va acid beo va duy tri lng ng trong mau. Cc hormone c th gy ra thay i ln trong chuyn ha vi nng thp l nh c s hot ng ca h thng khuch i tn hiu thng tin trao i cht mng t bo, trong quan trng nht l cc th th (receptor). Mi hormone c mt loi th cm th c hiu, i vi Insulin ta c th th Insulin. Cc nghin cu ch ra rng receptor mng t bo c vai tr sinh hc trong hot ng ca t bo, trong s nhn din, truyn tin, tc dng ca hormone. Trong khun kh bi tiu lun ny ti tm hiu v th th Insulin v mi quan h ca n vi bnh tiu ng, hy vng nhng kin thc ny s cung cp c s l thuyt cho nhng tm hiu su hn ca ngi c. Mc d trong qu trnh lm tiu lun ti c gng thu thp v x l ti liu nhng chc khng trnh khi thiu st, rt mong c c gio v cc bn gp . Ti xin chn thnh cm n. H Ni, ngy 10 thng 11 nm 2011

CHNG 1 GII THIU V INSULIN

1.1 Cu trc phn t Insulin Insulin l mt hormone protein do t bo beta ca tiu o Langerhans trong tuyn ty sinh ra. Phn t protein Insulin tng i nh, c khi lng khong 6000 Dalton (Da), c cu to bi 2 chui polypeptide A v B. Cc chui A v B lin kt vi nhau bng cc cu disulfua, ngoi ra cn c mt cu disulfua na nm trong chui A.

Hnh 1: Tuyn ty trong c th ngi hu ht cc loi, chui A bao gm 21 amino acid cn chui B c 30 amino acid. Mc d trnh t amino acid ca Insulin khc nhau gia cc loi nhng mt s on nht nh ca phn t li c tnh bo tn cao, cc on c cha v tr ca 3 cu disunfua, c 2 u ca chui A v nhnh bn ca ca u cacboxyl (-COOH) ca chui B. S tng ng trong trnh t amino acid dn n cu trc 3 chiu ca Insulin cc loi khc nhau rt ging nhau. Insulin tch chit t mt ng vt c kh nng hot ng sinh hc cao trong nhiu loi khc.

Cc phn t Insulin c xu hng to thnh dng dime trong dung dch do hnh thnh cc lin kt hidro gia cc u cacboxyl ca cc chui B. Ngoi ra, khi c mt cc ion km, cc dime Insulin lin kt to thnh hexame. Cc mi tng tc ny c ngha rt quan trng trong iu tr. Dng monomer v dng dime d dng khuch tn vo mu, trong khi dng hexame khuch tn rt km. Do s hp th cc thuc cha hm lng hexame cao thng b chm v ngng hn. Vn ny thc y s ra i ca mt s loi Insulin gi ti t hp. Loi cht u tin nh th c bn trn th trng l Insulin lispro, phn t cht ny c trt t Lysin v Prolin trn u cacboxyl ca chui B b o ngc. S ci bin khng lm mt kh nng gn vi th th ca Insulin nhng lm gim ti a khuynh hng hnh thnh dng dime v hexame.

Hnh 2: Cu trc phn t Insulin 1.2 Vai tr sinh hc ca Insulin Insulin l mt trong nhng hormone iu ha nng glucose trong mu. Chc nng cn bng ni mi v nng lng sinh hc ny cc k quan trng bi vi glucose l ngun nhin liu chnh ca h hp t bo v ngun khung cacbon quyt nh cn cho tng hp cc cht hu c. Cn bng trao i cht ph thuc vo vic

duy tr glucose mu gn mt im n nh, khong 90 mg/ml mu ngi (theo Campbell). 1.2.1 Tc dng ca Insulin ln qu trnh chuyn ha Hydratcacbon Glucose c gii phng t tinh bt, saccharose, v.v... nh thy phn khi tiu ha thc n, sau c hp thu vo mu rut non. Nng glucose cao trong mu kch hot s gii phng Insulin v Insulin hot ng trong cc t bo khp c th nhm thc y s hp thu, s dng v d tr glucose. Tc ng ca Insulin ln trao i glucose thay i ty theo m ch. Cc phn t Insulin tun hon trong dng mu cho ti khi chng gn vi th th ca chng trn mng t bo. Khi phc h th th - Insulin khi pht mt chui truyn tn hiu mang thng tin c pht ra bi Insulin: chuyn glucose ra khi huyt tng. Trong mt lot cc p ng t bo do s hot ha ca Insulin gy ra th cha kha trong trao i cht glucose l bc lm tng s hot ng ca protein vn chuyn glucose GLUT4 glucose transporter. Nh s vn chuyn thun li glucose vo trong t bo, cc GLUT4 loi glucose ra khi dng mu mt cch hiu qu. Nhng thay i nh vy ko di t vi pht n vi gi. GLUT4 c mt trn mng t bo ca nhiu loi m trong c th nh m c xng (t chy glucose lm nng lng), m m (chuyn glucose thnh triglycerit d tr) v m gan. * Lm tng s thoi ha glucose c Mng t bo bnh thng ch cho glucose khuch tn qua nhng rt t (tr khi c tc dng ca Insulin). Ngoi ba n ra lng Insulin c bi tit ra rt t nn glucose kh c khuch tn qua mng t bo c. Khi lao ng nng nhc, t bo c s dng mt lng ln glucose m khng cn mt lng Insulin tng ng (l do ca n th cha c r rng). Khi t bo c s dng nhiu glucose (vi gi sau ba n) lc ny nng ca g trong mu s tng ln cao, Insulin s

c bi tit ra nhiu hn nn lm tng s vn chuyn glucose vo cc t bo c. * Lm tng d tr Glycogen c Nu sau ba n m c khng vn ng th glucose vn c chuyn vo t bo c. Lng glucose m khng c s dng s c tch ly d tr di dng glycogen c dng khi c th cn thit. * Lm tng thu nhp, d tr v s dng glucose gan Mt trong nhng tc dng quan trng nht ca Insulin l lm cho hu ht glucose c hp th t rut vo mu sau ba n tr thnh glycogen d tr. Sau khi i th nng glucose trong mu gim xung, tuyn ty d gim s bi tit Insulin. Lc ny glycogen gan s c phn gii thnh glucose v lm cho nng glucose trong mu tng ln. C ch ca Insulin vi s lm tng thu nhp, d tr g gan nh sau: Insulin s lm mt hot tnh ca phosphorylase ca gan l enzyme phn gii glycogen thnh glucose. Insulin lm tng hot tnh ca enzyme glucokinaza l enzyme pht ng s phosphoryl ha glucose trong t bo gan. Khi glucose c phosphoryl ha th khng khuch tn qua mng tr li mu. V vy, Insulin lm tng thu nhp glucose vo t bo gan. Insulin lm tng hot tnh ca cc enzyme tham gia vo qu trnh tng hp glycogen gan. Khi lng glucose c a vo t bo gan qu nhiu th chng s c d tr li di dng glycogen nh ni trn hoc l di tc dng ca Insulin th lng glucose tha s c chuyn thnh acid bo v c chuyn n cc m lipid d tr li. * Lm c ch qu trnh to ra cc loi ng mi

Hnh 3: Insulin iu ha lng glucose trong mu Insulin c tc dng lm gim s lng v hot tnh ca cc enzyme tham gia vo qu trnh to ra cc loi ng mi. Insulin c tc dng lm gim s gii phng cc amino acid t cc t bo c va t cc m khc vo gan. Do vy lm gim cc nguyn liu ca cc qu trnh to ra cc ng mi. Nh c tc dng m Insulin c tc dng lm gim nng glucose trong mu. 1.2.2 Tc dng ca Insulin ln qu trnh chuyn ha lipid Insulin c tc ng quan trng ln qu trnh trao i lipit. Cc tc ng bao gm: * Lm tng s tng hp acid bo v vn chuyn acid bo n cc m m Di tc dng ca Insulin, mt mt lng glucose c s dng nhiu cho vic to ra nng lng nn tit kim c vic s dng ht s c to thnh cc acid bo gan v c chuyn n cc m m. Insulin lm tng s tng hp cc acid bo nh cc tc dng sau y:

Insulin lm tng s vn chuyn glucose vo cc t bo gan. Khi m nng ca glycogen t ti mc 5 - 6 % khi lng ca gan. Lc c s c ch khng cho gan tip tc tng hp glycogen na. Tt c lng glucose c vn chuyn thm ti gan s c to thnh pyruvat ri thnh acetyl CoA tng hp thnh cc acid bo. Khi glucose c s dng to thnh nng lng do tc dng ca Insulin th mt lng ln iso citrate c to thnh. Cc ion ny s hot ha enzyme Acetyl - CoA - Cacboxylasa l enzyme cn thit cho qu trnh sinh tng hp cc acid bo. Hu ht cc acid c to thnh gan s c s dng to thnh triglycerit l loi m d tr. Cc triglycerit c a t t bo gan vo mu dng lipoprotein lipaza c thnh mch mu ca m m. Enzyme ny s phn gii triglycerit tr li thnh acid bo v hp thu vo m m, ri acid bo li c chuyn tr li thnh triglycerit. * Lm tng s tng hp triglycerit t acid bo tng d tr lipid m m Insulin c 2 tc dng sau y: Insulin s c ch enzyme xc tc phn ng phn gii triglycerit l dng d tr lipid m m. Do vy lm gim s gii phng acid bo vo mu. Insulin c tc dng tng cng vn chuyn glucose qua mng t bo vo t bo lipid theo mt c ch tng t nh vn chuyn glucose qua mng t bo c. 1.2.3 Tc dng ca Insulin ln qu trnh chuyn ha protein * Ln qu trnh tng hp v d tr protein Vi gi sau khi n lng cc cht dinh dng c tng ln cao trong mu. Do vy, nhng glucose, acid bo v c protein cng c d tr m, do Insulin l rt cn thit cho qu trnh ny. C ch ca Insulin vi s lm tng d tr protein cn cha c r rang nh glucose hoc lipid. Tuy vy, ngi ta cho rng Insulin c cc tc dng ch yu sau y:

Insulin lm tng s vn chuyn tch cc nhiu amino acid vo trong t bo (valin, leucin, thyroxin....), sau cng vi hormone GH, Insulin lm tng kh nng thu nhp amino acid vo t bo. Insulin c tc dng ln ribosome lm tng s dch m RNA thng tin, sau to thnh cc phn t protein mi. Insulin cn lm tng s sao chp c chn lc phn t DNA nhn ca t bo ch t to thnh mt lng ln RNA thng tin cn thit cho qu trnh sinh tng hp cc phn t protein mi. * c ch s thoi ha ca protein Do vy lm gim tc gii phng amino acid ra khi t bo. * Tc dng ln s pht trin hnh th V Insulin c tc dng l lm tng s tng hp protein nn c tc dng tham gia vo qu trnh pht trin hnh th. 1.2.4 Cc tc ng ng ch khc ca Insulin Ngoi cc tc ng lm tng glucose i vo trong t bo, thc y s hp th cc amino acid, Insulin cng lm cho nhiu t bo tng tnh thm i vi cc ion kali, ion magie v phosphate v c, to iu kin thun li cho qu trnh phosphoryl ha v s dng glucose.

Hnh 4: Insulin lm tng tnh thm ion K, Mg v photphat v c

1.3 Tng hp Insulin trong c th Insulin c tng hp bi cc t bo tuyn ty beta. Cc t bo beta sp xp thnh cc b gi l cc o Langerhan trong ty. insulin c to ra t mt phn ca mt protein ln hn m bo s gp np ng.

Hnh 5: Tng hp Insulin trong c th

Hnh 6: Cc bc ci bin sau dch m ca phn t Insulin

ANRm tin hnh dch m mt protein gi l preproinsulin. Preproinsulin bao gm mt trnh t tn hiu u amin gip tin cht hoocmon ny i qua mng li ni cht tham gia vo qu trnh sau dch m. Ti qu trnh sau dch m, trnh t tn hiu u amin khng cn thit nn preproinsulin b thy phn to thnh proinsulin. Sau khi hnh thnh 3 cu ni disunfua mt s peptitdase s phn ct proinsulin to insulin hon chnh v hot ng.

Hnh 7: Proinsulin v insulin ngi 1.4 iu ha tng hp Insulin Bng c ch thn kinh v th dch * C ch thn kinh Di tc dng ca nhng iu kin nht nh kch thch vo thn kinh giao cm v ph giao cm c th lm tng s bi tit Insulin. Tuy vy h thn kinh thc vt t c tc dng trong vic iu ha bi tit Insulin trong trng hp bnh thng. * C ch th dch Vi nng ca glucose: Nu nng glucose trong mu tng ln cao t ngt gp t 2 n 3 ln so vi mc bnh thng th Insulin s c bi tit nhiu hn v do s lm tng vn chuyn glucose vo gan v c cng cc m khc lm gim nng glucose tr v mc bnh thng.

Vi nng ca amino acid: Mt s amino acid (arginin, lysine...) cng c tc dng n bi tit Insulin. Nu nng ca cc amino acid ny c tng ln th Insulin cng c bi tit ra nhiu hn. Tuy vy, nu ch n thun l amino acid th tc dng kch thch bi tit Insulin yu hn so vi tc dng ca glucose hay phi hp vi glucose. Mt vi hormone ti ch: Do thnh ca ng tiu ha bi tit ra nh gastrin, secretin... cng c tc dng kch thch tng hp Insulin.

CHNG 2 GII THIU V BNH TIU NG

2.1 Dch t hc Tiu ng (diabetes) l bnh ri lon v chuyn ha cacbohydrat, trong ng trong mu khng b oxi ha gii phng nng lng m tch t trong mu mc cao (> 1,2g/l) gi l tng ng huyt. M, hng nm c khong 17 triu ngi (6%) dn s mc bnh tiu ng, gy t vong cho 400.000 c dn Hoa K v ng th 6 trong cc bnh gy cht ngi. Tiu ng ph bin nht tui trn 45 tui, i vi nhng ngi bo ph, t hot ng, nhng ngi c ngi thn b mc bnh v nhng ngi Chu Phi, Ty Ban Nha, ngi M bn x. T l mc bnh n gii cao hn nam. Ti Vit Nam, trong 4 thnh ph ln H Ni, Hu, Thnh ph H Ch Minh, Hi Phng, t l bnh tiu ng l 4%, ring qun Hon Kim (H Ni) ln ti 7%. Phn ln ngi bnh pht hin v iu tr mun, h thng d phng, pht hin bnh sm nhng cha hon thin. V vy, mi nm c trn 70% bnh nhn khng c pht hin v iu tr. T l mang bnh tiu ng la tui 30-64 l 2,7%, vng ng bng, ven bin 2,2%, min ni 2,1%. Nu khng c phng chng v cu cha kp thi, bnh d bin chng, 44% ngi bnh i tho ng b bin chng thn kinh, 71% bin chng v thn, 8% b bin chng mt. Hin trn th gii c lng c hn 190 triu ngi mc bnh tiu ng v s ny tip tc tng ln. c tnh n nm 2010, trn th gii c 221 triu ngi mc bnh tiu ng. Nm 2025 s ln ti 330 triu ngi (gn 6% dn s ton cu). T l bnh tng ln cc nc pht trin l 42%, nhng cc nc ang pht trin (nh Vit Nam) s l 170%. 2.2 Phn loi, nguyn nhn, triu chng v hng iu tr

 nhng bnh nhn b tiu ng, hm lng glucose trong mu cao, lm tng p lc thm thu nhng qu trnh hp th glucose vo mu li yu. Khi hm lng glucose cao vt qu ngng hp th ca thn th c quan ny s o thi glucose theo nc tiu dn n nc v ion cn thit cho s trao i cht qua mng t bo ra ngoi. C hai loi tiu ng chnh: 2.2.1 Tiu ng typ I Tiu ng typ I hay cn gi l tiu ng ph thuc insulin (IDDM -Insulin Dependent Diabetes Mellitus). * Triu chng Xut hin t ngt, nhanh nh n nhiu, ung nhiu, st cn nhanh, gim th lc, nng tnh, mt mithng gp tui thanh nin (< 30 tui), chim t 1015% s ca * Nguyn nhn Cc t bo beta tuyn ty b ph hy, dn n thiu ht tng lng insulin. Cc t bo ny b ph hy c th do nhiu nguyn nhn khc nhau. Do bnh t min, khi c th tip xc hay b nhim mt loi virut tim n , cht cc th p li bng cch to khng th chng tc nhn gy hi . Nhng khng nguyn virut li ging vi khng nguyn t bo tuyn ty nn khng th c hnh thnh chng tc nhn gy hi cng chng li m tuyn ty, gy ph hy t bo beta. y l phn ng t min. Cc nh khoa hc xc nh c 20 gen ng vai tr mn cm vi tiu ng typ I , mc d chc nng ca n cn ang c nghin cu. i vi h tiu ng typ I, iu tr, ch cn b sung thm insulin l c th duy tr c s sng cho ngi bnh. i vi nhng bnh nhn b tiu ng typ I khng th kim sot tt ng huyt bng cc loi thuc ung th s dng liu php Insulin tch cc l cha kha bnh nhn kim sot ng huyt ca mnh v ngn nga cc bin chng do bnh gy ra. Liu php insulin tch cc c

th ngn nga hoc lm chm tin trin cc bin chng mn tnh ca bnh T, c bit l cc bin chng thn, mt, tim mch... Kt qu cc nghin cu cho thy, liu php insulin tch cc c th: lm gim nguy c b bin chng mt ti hn 75%; lm gim nguy c b bin chng thn kinh ti 60%; v ngn nga hoc lm chm tin trin cc bin chng thn ti 50%. Ngoi ra, n cn em li nhiu li ch khc. V d cc bnh nhn iu tr insulin tch cc, kim sot tt ng huyt thng cm thy khe hn, tng cn v tng kh nng hot ng th lc, lm vic... Liu php insulin tch cc l mt phng php iu tr tch cc c thit k nhm kim sot ng huyt ca ngi bnh cng gn mc ca ngi bnh thng. Liu php ny i hi ngi bnh phi tim nhiu mi insulin v kim tra ng huyt thng xuyn hng ngy. V mc tiu, cc bnh nhn iu tr insulin tch cc nhm kim sot ng huyt trong mc l tng l: ng huyt trc ba n t 90 130 mg/dL; ng huyt sau ba n 2 gi nh hn 180 mg/dL; hemoglobin A1C (ch s nh gi kim sot ng huyt trong vng 3-4 thng) di 6,5%. Ngoi ra, theo t MedNews, 5/2007, mt s nh khoa hc c mt cng trnh nghin cu v phng php s dng t bo gc iu tr bnh tiu ng typ 1 bng cch phc hi chc nng ca t bo tuyn ty beta. Khi mt ngi ln u tin c chn on l mc bnh tiu ng, ngi vn cn mt s t bo bta cn kh nng thc hin chc nng sn xut insulin, bi vy cc nh khoa hc tm cch ngn chn s ph hu tip theo. Nhng cng trnh nghin cu trc y v cc khng th phong to nhng t bo min dch b ph hu chng t l thnh cng trong mt thi gian nht nh. mt cng trnh nghin cu mi y, liu php min dch c kt hp vi cc t bo gc cy vo bnh nhn, xem ra ci thin c chc nng ca cc t bo bta.

 cng trnh nghin cu ny, do cc nh khoa hc trng i hc Sao Paulo, Braxin v Northwestern, Chicago thc hin, cc t bo gc thu c t mu ca bnh nhn. Tip , chng c tin hnh mt dng ho tr liu khi b t bo min dch tiu dit. Sau khi cc bnh nhn c tim t bo gc, h c theo di v mc ph thuc insulin v chc nng ca t bo bta. Kt qu cho thy 13 trong s 15 bnh nhn c iu tr bng phng php ny c th khng cn phi tim b sung insulin trong khong thi gian t 9 thng n 3 nm. Cc chuyn gia cnh bo rng nhng kt qu trn vn cn mang tnh s b v cn phi tin hnh nhiu nghin cu hn na. Tuy nhin, l mt phng php y ha hn, v xem ra n khng gy ra cc tc dng ph v do rt ng c tin hnh. Php iu tr ny ch c cng hiu i vi nhng bnh nhn mi b mc bnh, bi v h vn cn cc t bo bta nguyn vn thc hin chc nng. Cc nh khoa hc cng ang tm kim cc liu php khc cho nhng bnh nhn mc bnh lu. Tiu ng typ 1 nu khng c iu tr c th nh hng n c ch chuyn ha cht bo. Do c th khng chuyn ha glucose thnh nng lng, nn cht bo s c dng cung cp nng lng. iu ny dn n tng hm lng cc hp cht c tnh axit trong mu ( th ketone) can thip vo qu trnh h hp ni bo. 2.2.2 Tiu ng typ II Tiu ng typ II, cn gi l tiu ng khng ph thuc insulin (NIDDMnon-insulin-dependent-diabete mellitus. * Nguyn nhn Khi gii phu bnh l vi th o ty cho thy: ch c 25% bnh nhn tiu ng c gim tit Insulin, 25% khng gim tit v 50% t bo beta tng tit. Nh vy tiu ng typ II c trng bi s thiu ht insulin, hoc ph bin hn l gim

tnh p ng ca cc t bo ch i vi insulin do mt s thay i th th dnh cho n trn mng t bo. * Triu chng Bao gm cc triu chng ca tiu ng typ I, v mt s triu chng khc nh vim da, s hi phc vt thng chm hoc kh phc hi, thng ch c pht hin bi cc triu chng ca bin chng, hoc ch c pht hin tnh c khi i xt nghim mu trc khi m hoc khi c bin chng nh nhi mu c tim, tai bin mch mu no; khi b nhim trng da ko di; bnh nhn n hay b nga vng do nhim nm m h; bnh nhn nam b lit dng Loi tiu ng typ II chim khong 90% s ca b bnh tiu ng. Tiu ng typ II thng xut hin nhiu la tui trn 45. Do cc triu chng ca n xut hin chm nn ngi bnh c th khng nhn bit c ngay h ang mc bnh. Mc khc, cc nh khoa hc cho rng c mi lin quan cht ch gia bo ph v tiu ng typ II. Khong 80% s ngi bo ph b tiu ng typ II. Vic cha tr loi bnh ny phi kt hp gia tp luyn v ch n ung gim s khng insulin v tng cng vic tit insulin. Ch dng lng hidratcacbon cho nhu cu c th. Ngoi ra, s dng thm thuc h ng huyt nh sunfamid hay biguanid. Trong trng hp tht bi, cn phi iu tr bng tim insulin n thun hay phi hp vi thuc vin ung. 2.3. Bin chng Tiu ng typ I khi b bin chng c th dn n hn m ng huyt (mt trng thi v thc gy ra do lng ng cc k cao trong mu) hoc t vong. C tiu ng typ I v II u c bin chng m, thn h v bnh tim. Tiu ng c th khin cc mch mu nh b tc; nu iu ny xy ra cc mch mu mt th s gy bnh vng mc, dn n m. Tiu ng khin cho thn mt kh nng lc cht c (khong 40%). Tc mch mu ln d dn n vn v tim

mch (cao huyt p, nhi mu c tim v t qu), nguy c cao gp 2-4 ln nhng ngi khng b tiu ng. Tiu ng cn c kh nng gy tn thng thn kinh ngoi bin, mt cm gic, c bit chn, tn thng thn kinh thc vt v nhim trng.

Hnh 8: C ch bnh tiu ng gy ra bin chng 2.3.1 Bin chng mt M mt v m lo l nhng bin chng thng xy ra ngi bnh tiu ng. - Bin chng dy thn kinh no (cranial nerve palsies): lit thn kinh th gic (cranial nerve III), thn kinh vn ng trong v ngoi ca mt (cranial nerves IV & VI) a n ri lon th gic (thy mt thnh hai-double vision) v ri lon vn ng mt (mt l-motility disorders). - Bin chng tinh th (lense) a n vy c hay cm mt (cataract), c th lm tng p nhn (glaucoma) v b m lo.

- Bin chng thy tinh th (vitreous) a n chng cm xanh (vitreous hemorrhage) c th a n m lo. - Bin chng vng mc (retina) lm xut huyt (bleeding), v trc vng mc do xut huyt (retina detachment), v nhng mch mu mi xut hin nhiu lm m mt (neovascularization) v cng a n m lo. - Bin chng con ngi (iris) do nhng mch mu mc nhiu (neovascularization) nhng thiu dng kh (oxygen) Thng nhng bin chng mt xut hin trong vng 5 nm nu bnh khng c iu tr.

Hnh 9: Nhng bin chng mt do bnh tiu ng 2.3.2 Bin chng thn Bnh tiu ng loi 2 gy ra 60% ca tt c cc trng hp suy thn (kidney failure) v cn phi c lc mu (kidney dialysis). Ghp thn (kidney transplant) do bnh tiu ng ng hng u chim tng s 40% cc trng hp. Bin chng ny xy ra nhiu da en v da mu.

Hnh 10: Cc giai on dn n suy thn trong bnh tiu ng type 2.

2.3.3 Bin chng tim v mch mu

Hnh 11: Bin chng tim v mch mu Thng bnh nhn n vi bc s l nhng triu chng thiu mu c tim (ischemic heart disease), kh th do suy tim (heart failure), tai bin mch mu no (stroke), hoc chn b l khng lnh, v cc v bc s pht gic ra bnh nhn ca mnh c tiu ng loi 2. Ngi bnh tiu ng loi 2 c c hi b bnh v tim 2-4 ln ngi bnh thng. Nu h ht thuc th con s ny s ln n 10 ln nhiu hn. V th, vic b thuc l rt l quan trng. Bin chng ny xy ra sau khi mch mu tim hay ng mch

c (carotid arteries) hay chn tay b ngn n 90%, triu chng mi bt u xut hin. * tim: au ngc (chest pain) km theo kh th (short of breath). Ngi bnh c cm gic nh c mt ngi nng 500 cn (lbs.) ngi ln trn ngc ca mnh. au c th lan ln n vai tri v c (left shoulder and neck). au lan xung tay tri. l triu chng thiu mu c tim (ischemic heart/angina). Nu triu chng ko di hn 20 pht, bnh nhn b nhi mu c tim (heart attack/myocardial infarction) v ua n try tim mch (cardiovascular collapse). Bnh nhn cht nu khng iu tr kp thi. Bnh ny nhiu nht ngi tr tui (di 65 tui). T 18-44 tui c bin chng tim nhiu hn ngi bnh thng 4 ln. T 45-64 tui co bin chng tim 3 ln nhiu hn ngi bnh thng. 65 tui hay ln hn c bin chng tim 2 ln nhiu hn ngi bnh thng. * Tai bin mch mu no (stroke):

Hnh 12: M bm trong thnh ng mch c Thng xy ra ngi bnh tiu ng ln hn 65 tui. Chim t l 9% ca tt c cc ngi b bnh tiu ng. la tui 45-64 tui, ngi b bnh tiu ng c bin chng ny nhiu hn ngi bnh thng cng la tui 5 ln. Bin chng ny do m ng trong thnh mch mu no. Nhng mnh v ca lp m

ny to ra s tc nghn mch mu. Hoc thnh mch mu qu cng d b v v gy ra xut huyt trong no. * chn, tay: au chn hoc tay khi lm vic hay i b. Nu ngh ngi, s au n s thuyn gim (claudication). Nng hn na, chn hay tay b l lot v thi (gangrene). n giai on ny phi ca chn hay tay. Bin chng tim mch xy ra rt nhanh nu bnh nhn ht thuc. Bnh l lot chn chim 15% s ngi bnh tiu ng trong sut cuc i ca h. 6-43% ngi bnh tiu ng b ca chn. 55% ngi bnh tiu ng b ca chn xy ra ngi ln hn 65 tui. 2.3.4 Bin chng acid ha v tng p lc phn t trong mu (Ketoacidosis and Hyperosmolarity) a) Bin chng acid ha Bin chng ny thng xy ra khi ng trong mu tng qu 30 mmol/L (545 mg/dL). Thng xy ra bnh tiu ng loi 1. bnh tiu ng loi 2, bin chng ny rt him khi xy ra. N phi c nhng iu kin thun li trc (predisposition factors) nh c ketone trong mu v acid ha mu (trong trng hp bnh nhn n t cht bt/ low carbohydrate v nhiu tht & m to ra tnh trng ketosis v mild acidosis). Bin chng ny xy ra rt nhanh. Nu khng iu tr kp thi, bnh nhn c th cht trong vng vi gi cho n vi ngy. Bin chng xy ra khi ketone tch t nhiu trong mu v nng acid cao hn bnh thng. Chng ta c th ngi thy mi ketone (ging nh mi thuc ra mng tay ca qi b) trong hi th ca bnh nhn. b) Bin chng tng p lc phn t Ging nh bin chng va k trn, khi ng ln cao qa nhng khng c ketone v acid ho mu. Khi ng trong mu ln qu cao, lm kh nc trong cc t bo v cc c quan ni tng. Bnh nhn bt u vi i tiu nhiu v kht nc nhiu, sau ngi l v hn m.

Hai bin chng trn thng xy ra khi bnh nhn tiu ng loi 2 khng c cha tr v c mt hay nhiu bnh cp tnh (acute ilnesses) i km theo nh nhim trng nng, nghn rut, phng nng (severe burn) 2.3.5 Bin chng ca thn kinh Bin chng ca dy thn kinh gy bi ng trong mu ln cao lm h hi nhng mch mu bn cnh dy thn kinh hoc mch mu nui dy thn kinh. S thiu mu hoc chn p dy thn kinh a n nhng h hi ca dy thn kinh. N lm nh hng n s dn truyn ca dy thn kinh. Cng vi nhng yu t di truyn v chn thng nhiu ln nh hng ln nhng h hi ny, gy ra bin chng ca dy thn kinh. Thng nhng bin chng ny a n ca chn hoc tay (amputation. Thng nhng triu chng khi u l: - au, rt. - Mt cm gic v s m (tactile sensation), cm gic nng lnh (thermal sensation). - Bi lit (motor) mt phn c th nh l mt, mt vt c hai hnh (diplopia) Bin chng c th nh hng n mt vng nh (focal neuropathies) hay mt vng rng ln (diffuse neuropathies). 2.3.6 Nhng bin chng da v nhim trng Hu ht nhng ngi bnh tiu ng loi 2 c h thng min nhim yu i do ng mu cao nh hng n. Nhng nhim trng thng xy ra. Khi nhim trng xy ra, ng mu s ln cao mc d chng ta c iu tr nhiu loi thuc khc nhau. Cho nn, mt ngi vi tiu ng loi 2 kh kim sot ng mu, iu u tin l ngi bnh khm tng qut nht l v nhim trng. Ngoi ra, nhim trng d dy do vi khun Helicobacter pylori v nhng nhim trng mt, c hng v c quan sinh dc do vi khun Chlamydia trachomatis thng gip lm v nhng mnh m ng trong thnh mch mu v gy ra nhi mu c tim

(myocardial infarction) hay tai bin mch mu no (stroke). T l nhng vi khun ny c tm thy trong 2 bin chng va k ln n 30%. Nu chng ta khng iu tr nhng vi khun ny, 2 bin chng tim v no s xy ra tr li. Ngoi ra, vi khun Staphylococci v Helicobacter pylori cng gy ra nhim trng ngoi da lu ngy s to ra nhng bnh ngoi da kinh nin nh bnh vy nn (psoriasis vulgaris). 2.3.7 Nhng bin chng khc Bnh tiu ng gy bin chng hu ht cc c quan ca c th ca ngi bnh. Hu ht, cc bin chng gy bi ng trong mu ln cao lu ngy. iu quan trng nht l chng ta gi ng trong mu bng vi ngi bnh thng. Nhng ngi qu yu, ta gi ng cng gn mc bnh thng cng tt. N gip ta gim bin chng nhng iu tt nht l ta chn bnh tiu ng loi 2 trc khi n xy. iu ny hin nay chng ta c th lm c d dng nu chng ta hiu c th no l bnh tiu ng loi 2 v t quyt tm nga n.

CHNG 3 TH TH INSULIN V MI QUAN H CA N VI BNH TIU NG

3.1 Th th Insulin 3.1.1 Cu trc Receptor dnh cho insulin chnh l mt protein kinase chuyn nhm phosphat t ATP n cho nhm hydroxyl ca gc tyrosine (khng phi cho Ser hoc Thr). Th th insulin gm c hai chui ging nhau nh ra pha mt ngoi ca mng sinh cht v hai tiu n v xuyn mng c tn cng C nm pha ni bo. Cc chui cha cc vng lin kt vi insulin v cc chui c vng hot tnh tyrosine kinase.

Hnh 13: Th th Insulin

Th th insulin c dng cu trc phn t ging vi hng lot th th hormon khc v cng tng t nh cu trc ca th th nhn bit yu t sinh trng. Tt c chng u ging nhau v cu trc v u c hot tnh tyrosine kinase. Chng hn cc th th EGF (yu t tng trng biu b) v PDGF (yu t tng trng bt ngun t tiu cu) u c cu trc v trnh t acid amin gn ging nhau v u c hot tnh tyrosine kinase vng tn cng C nm trong t bo.

3.1.2 Hot tnh tyrosine kinase Hnh 14 : AMP vng - nhn t quyt nh n hot tnh ca Protein kinase A

Insulin lin kt vi cc chui , hot ho hot ng tyrosine kinase ca cc chui . Trc tin enzym phosphoryl ho cc gc tyrosine ca chnh bn thn chui v s t phosphoryl ho ny to cho enzym tip tc phosphoryl ho cc protein khc ca mng hoc ca t bo cht (cytosol). Mc d trnh t chi tit ca cc s kin cho php hiu bit su sc s kch thch ca insulin i vi qu trnh hot ho cha c y nhng dng nh s lin kt ca insulin vi th th ca n s khi u mt dng thc (cascade) phosphoryl ho, trong th th hot ho protein kinase th hai, tip theo protein li hot ho protein th ba hoc serine kinase hoc threonine kinase. Cui cng s phosphoryl ho cc gc Ser hoc Thr lm bin i hot tnh ca mt hoc nhiu enzym quan trng i vi chc nng ca t bo. Nh vy, insulin tc ng trng ch ca n. Cc bnh nhn b bnh tiu ng typ II i khng insulin vn tit insulin bnh thng nhng cc m ca chng khng tr li i vi insulin ca bn thn hoc i vi insulin c tim vo c th. nhng ngi mc bnh ny vng hot tnh tyrosine kinase ca th th insulin b t bin. Insulin vn lin kt bnh thng vi th th t bin nhng vng tyrosine kinase ca th th b bt hot v hu qu lin kt ca insulin khng xy ra theo hng bnh thng.

Hnh 15: C ch tc ng ca Insulin iu ha nng glucose trong mu 3.2 iu ho lng ng trong mu C th hp th glucose theo 2 con ng: trc tip t thc n v gin tip t cc acid amin v lactate thng qua qu trnh tn to glucose. Glucose cung cp nng lng c th oxy ho cho cc m duy tr s sng. Lng glucose c tiu th hng ngy ch yu l do cc hot ng ca b no (75%) thng qua con ng hiu kh. Cn li l do hng cu, c xng v c tim tiu th.

Lng glucose bnh thng trong c th l 12 mg/l (khong 6mM). Khi lng glucose trong mu tng ln th n c tch lu di dng glycogen, nm ch yu trong gan, c v mt phn trong thn v rut. Glycogen c gp 2 ln thn. Glycogen c khng th c sn cung cp cho cc m v c thiu enzyme glucose-6-phosphatase. Glycogen tch lu gan c xem l cht d tr chnh ca ng trong mu. Khi c th mt mi, du hiu ca s thiu glucose, th glycogen s b phn gii. S iu ho lng ng trong mu c thc hin thng qua 2 con ng chnh l phn gii v tng hp glycogen. 3.2.1 iu ho phn gii glycogen Qu trnh phn gii glycogen c thc hin nh enzyme glycogen phosphorylase. N l mt enzyme ng nh chui, c 2 dng ng phn l mch thng T v dng hot ng R. Khi dng R, chng c th lin kt vi glycogen. Cu trc R ny c tng cng nh s lin kt ca ATP v b c ch bi vic lin kt vi ATP hoc glucose-6-phosphate. Nh qu trnh phosphoryl ho m enzyme ny thc hin qu trnh bin i ho tr nh mt cch iu ho hot tnh ca n. Hot tnh tng i ca enzyme phosphorylase khng b ci bin to ra glucose-1phosphate, xm nhp vo qu trnh phn gii glycogen, cung cp ATP duy tr s sng. Khi lng ng trong mu thp, tuyn tu tit ra glucagon, mt polypeptit di 29 acid amin, lin kt vi cc th th b mt t bo gan v mt vi t bo khc, lm hot ho adenylate cyclase. Vic hot ho ny dn ti vic tng cng s hnh thnh cAMP. Khi cAMP lin kt vi cc tiu n v iu ho ca PKA s dn ti vic gii phng v hot ho tip ca cc tiu n v c chc nng xc tc. Cc tiu n v sau s b phosphoryl ho mt s protein cha gc Serine v Threonine. S phosphoryl ho ca enzyme PKA s hot ho enzyme ny ri bn thn n s phosphoryl ho enzyme phosphorylase-a bt hot thnh dng phosphorylase -b. Ezyme phosphorylase b sau tng hot tnh v tin hnh phn

hu glycogen. Cng lc , qu trnh phosphoryl ha glycogen synthase li km hm hot ng ca enzym ny. Dng bt hot ca glycogensynthase chnh l dng b phosphoryl ho.

Hnh 16: C ch iu ho phn gii glycogen thng qua con ng bt hot glycogen synthase PKA: Protein kinase ph thuc vo cAMP. PKC: Protein kinase C, mt dng kinase hot ng ph thuc Ca2+ (80kDa) PPI-1: Cht c ch phosphoprotein phosphatase - 1 PLC: Phospholipase C- phn gii P1P2 IP3 + DAG Epinephrine (adrenalin) l hormon tuyn thng thn c tc dng tr li li cc tn hiu thn kinh, cn cho vic tng cng s dng glucose ca c. Khi hormon ny lin kt vi cc th th trn b mt t bo c gy ra qu trnh phn hu glycogen tng t, nhng ng thi cng gy ra s bt hot enzym tng hp glycogen l glycogen sythase bng mt c ch phosphoryl ho enzym ny. S iu ho hot tnh PK (kinase ca phosphorylase) cn chu nh hng ca hai c ch khc nhau, lin quan n ion Ca2+. Mt l thng qua hot ng chc

nng ca mt tiu tiu n v ca PK l Calmodulin m Ca2+ c th iu ho c enzyme ny. Khi calmodulin lin kt vi Ca2+ ,n c tc dng lm tng hot tnh xc tc ca PK i vi c cht ca n, (phosphorylase b). Do s phn gii glycogen trong cc t bo c c tng cng khi c s kch thch co c nh acetylcholine. Khi acetylcholine c gii phng t cc synap c thn kinh, n s kh cc t bo c, dn ti vic tng cng phng thch Ca 2+ ca t bo c, qua hot ho PK. V vy, khi Ca2+ ni bo tng ln s lm tng t l co c, tng s phn gii glycogen, gii phng ATP. Con ng th hai l con ng trung gian thng qua s hot ho ca adrenalin i vi cc th th -adrenergic (hnh 10).

Hnh 17: iu ho phn gii glycogen bng kinase ca phosphorylase nh s hot ho epinephrine i vi cc th th -adrenergic PLC-: phospholipase C-. PIP2: phosphatidyl inositol - 4,5- bisphosphate, c cht ca PLC-. IP3: inositol triphosphate. DAG: diacyl glycerol.

PK: Phosphorylase kinase (kinase ca phosphorylase) Th th -adrenergic ghp cp thng qua protein G hot ho PLC-, qua lm tng s thu phn ca PIP2 mng t bo, to ra sn phm l IP3 v DAG. DAG lin kt v hot ho PKC (Protein kinase C), mt enzyme phosphoryl ho nhiu c cht. Mt trong nhng enzyme c phosphoryl ho nh PKC l glycogen synthase. Khi IP3 lin kt vi th th trn b mt ca li ni cht, s gii phng ra Ca2+. Ca2+ sau s tng tc vi cc tiu n v calmodulin ca PK (kinase ca phosphorylase) ri hot ho PK. Ca2+ cng hot ho PKC khi lin kt vi DAG. kt thc hot ng ca enzyme hot ho glycogen phosphorylase cn phi c qu trnh loi b nhm phosphate cho enzyme hot ho tr v dng enzyme bt hot. Trong trng hp Ca2+ cm ng s hot ho th nng Ca 2+ gii phng ra t t bo c phi c kt thc khi cc tn hiu thn kinh ngng li. S loi b nhm phosphate ca PK i vi phosphorylase b c thc hin nh enzym phosphoprotein phosphatase (PP-1). y l enzym phn gii tch gc phosphate ca cc phospho protein. Hot tnh ca PP1 cn phi c iu ho khi cc gc phosphate nh v trn cc enzyme c loi b ngay. iu ny s c hon thnh khi PP1 lin kt vi cht c ch PPI-1. PPI ch lin kt c vi PP1 khi n b phosphoryl ho bi PKA. ng thi, n cng b kh phosphoryl ho nh PP1 (hnh 11). 3.2.2 S iu ho tng hp glycogen Glycogen synthase l enzyme tng hp glycogen, tn ti dng tetremer v c 4 tiu n v ging nhau. S phosphoryl ho cc gc Serine ca cc tiu n v ny s iu ho hot tnh ca glycogen synthase. trng thi khng phosphoryl ho, enzyme c hot tnh v khng cn glucose-6-phosphate nh mt cht hot ho v ngc li. Hai dng enzyme ny l ng nht bi cng mt h danh php khi c s dng cho glycogen phosphorylase. Dng hot ng khng b phosphoryl ho l synthase-a, cn dng ph thuc vo glucose-6-phosphate l synthase-b l dng

b phosphoryl ha ( gn phosphat) l dng bt hot. S phosphoryl ho synthase xy ra tr li li s hot ho hormon ca PKA. Kinase ca synthase phosphorylase cng l enzyme phosphoryl ho glycogen phosphorylase. C t nht 5 enzyme phosphoryl ho trc tip glycogen synthase. Trong s c PKA, mt enzyme phosphoryl ho glycogen synthase quan trng, hot ng c lp vi vic tng nng cAMP l GSK-3. S phosphoryl ho ca mi enzyme xy ra cc gc Serine khc nhau.

Hnh 18: iu ho tng hp glycogen thng qua con ng phosphoryl ha v dephosphoryl ha (theo King, 1996) GSK: protein kinase ph thuc vo calmodulin, l glycogen synthase kinase (enzym phosphoryl ha glycogen synthase).

CK I, II l 2 dng Casein kinase. Glycogen synthase b dng bt hot (-ve) l dng c phosphoryl ha. Hot tnh ca glycogen synthase cng c th b nh hng khi epinephrine lin kt vi cc th th -adrenergic thng qua con ng iu ho glycogen phosphorylase. Khi th th -adrenergic b kch thch th s hot ho ca PLC-g v s thu phn PIP2 tng ln. Sn phm ca qu trnh thu phn PIP2 l DAG v IP3. DAG v ion Ca++ c gii phng ra nh IP3 hot ho PKC, enzyme phosphoryl ho v bt hot glycogen synthase. S phn hi ca Ca++ l s hot ho PKC. nh hng ca qu trnh phosphoryl ho dn ti nhng hiu qu sau: 1. Gim i lc ca synthase i vi UDP-glucose. 2. Gim i lc ca synthase i vi glucose-6-phosphate. 3. Tng i lc ca synthase i vi ATP v Pi. S chuyn ho tr li ca synthase b bt hot thnh synthase a l dng hot ng i hi s kh phosphoryl ho bi PP1 (Phosphoprotein phosphatase). Hot tnh ca PP1 cng chu nh hng ca insulin, mt hormon tuyn ty c tc dng ngc li vi glucagon v epinephrine. 3.3 Insulin v cc protein vn chuyn glucose Hin nay ngi ta tm ra 12 loi protein vn chuyn glucose (Glucose Transporters GLUT) c m ho trong genom ca ngi v c k hiu l: GLUT 1, GLUT2, GLUT3, GLUT4... .v.v. GLUT 1 c mt tt c cc m t bo v c chc nng iu ho tng th s cn bng hp thu glucose. GLUT2 c mt ch yu m gan, o ty v cc m rut, GLUT3 c mt m no thn kinh, GLUT4 ph bin cc t bo c xng, m m v tim. ng ch l nh cc GLUT1 s vn chuyn glucose t ngoi t bo vo hng cu tng gp 50 ngn ln so vi khng c s xc tc ca GLUT1. GLUT1 l mt protein c khi lng 45kDa, vi 12 mnh k nc xon xuyn qua mng lipid.

Vai tr ca insulin l lm tng cng hot ng ca GLUT4, trong khi GLUT2 thc hin chc nng ly i s d tha ca glucose trong mu sau cc ba n cha nhiu ng v iu ho s gii phng insulin o ty. Do s hot ng v tn thng ca cc GLUT2, GLUT4 c lin quan cht ch ti bnh tiu ng, c bit l bnh tiu ng typ I. Qu trnh vn chuyn glucose qua mng c th c m t tng t nh mt phn ng enzym trong "c cht" l glucose ngoi mng t bo (S-out) v "sn phm" ca phn ng l glucose bn trong t bo (S-in) v enzym c coi l GLUT (k hiu T). Ngi ta thit lp c phng trnh tc ca qu trnh vn chuyn glucose theo Michaelis-Menten :
v0 = Vmax[ S] out K t + [ S] out

Trong , v0 l tc tch lu ban u glucose ni bo khi nng ca n mi trng xung quanh l Sout v Kt l hng s vn chuyn tng t Km trong phng trnh Michaelis-Menten GLUT 4 c mt t bo c xng v c tim, t bo m m c hot ng tng ln nh tc dng ca insulin c phng thch t o tu vo mu. C ch iu ho s hp th Glucose t mu a vo t bo c v t bo m m ( chuyn ho thnh triacylglycerol) sau ba n nhiu cht ng (carbohydrate) nh hot ng ca GLUT 4 nh sau: Gia cc ba n ch c mt s GLUT 4 c mt trn b mt t bo, nhng chng c rt nhiu trong cc bng mng bn trong t bo. Khi nng glucose trong mu tng ln sau ba n s c tn hiu insulin c phng thch vo mu lm gim nng glucose ca mu. Th th tip nhn insulin trn mng bng c ch hot ng tyrosine kinase ca chnh th th truyn tn hiu huy ng cc bng mng cha GLUT 4 di chuyn ln b mt mng bng c ch dung hp vi mng sinh cht bc l cc GLUT 4 vi nng cao trn b mt t bo lm cho tc thu np glucose ca t bo tng ln 15 ln hoc ln hn so vi bnh thng. Khi nng insulin trong mu gim i, cc GLUT4 b mt s c di

chuyn vo ni bo bng c ch nhp bo (endocytosis) to thnh cc bng mng cha GLUT 4 bn trong t bo. Trong bnh tiu ng tp I, do t bo tu o b ph hu nn tn hiu tit insulin b mt, do kh nng hot ng di chuyn ca GLUT4 trn b mt t bo khng thc hin c. Hu qu l bnh tiu ng tp I xut hin. Trong trng hp bnh tiu ng tp II, vai tr ca th th insulin khng c thc hin do b tn thng cu trc ca cc phn tiu n v c hot tnh tyrosine kinase b t lit hoc t bin cu trc hoc do ri lon chc nng trao i cht.

KT LUN
Insulin l mt hormone protein c tit ra t tuyn ty c nhiu tc ng khc nhau nhng quan trng nht l iu ha lng glucose trong mu. Khi lng Insulin sn xut ra b thiu ht hoc t bo ch gim tnh p ng vi n th s gy ra bnh tiu ng. y l mt trong nhng cn bnh e da nghim trng n sc khe con ngi do n cn ko theo nhiu bin chng nguy him khc. C hai th bnh tiu ng l tiu ng typ I v tiu ng typ II. Receptor ca Insulin l mt protein kinase chuyn nhm phosphat t ATP n cho nhm hydroxyl ca gc tyrosine

TI LIU THAM KHO

1, Ngc Lin, Sinh hc phn t mng t bo, NXB i hc quc gia H Ni, 2007. 2, Phm Vn Ty, Nguyn Vn Thnh, Cng ngh sinh hc, tp nm, Cng ngh vi sinh v mi trng, NXB Gio dc, 2005. 3, http://daithaoduong.com 4, http://daithaoduong.net 5, http://duocnamlang.com 6, http://tieuduong.vn 7, http://www.ykhoanet.com