metabolic changes in diabetes mellitus.pptx

8/17/2019 METABOLIC CHANGES IN DIABETES MELLITUS.pptx

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DEPARTMENT OF BIOCHEMISTRY

SITI ANNISA DEVI TRUSDA

METABOLIC CHANGES IN DIABETES MELLITUS

AND DIABETIC PREGNANT

WOMAN


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Humans are able to use a ar!able

"uel !n#ut to meet a ar!ablemetabol!$ %eman%


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REGULATION O& BLOOD GLUCOSE LEVEL


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8

D!s#os!t!on o" 'lu$ose( am!no a$!%s( an%"at

b) ar!ous t!ssues !n t*e +ell,"e% state


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9

METABOLIC CHANGES IN T-PE,. DM / IDDM 0


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10

C*an'es !n Carbo*)%ratesMetabol!sm

+*!le !nsul!n *as 1 roles !n $arbo*)%ratemetabol!sm

.2 In$rease 'lu$ose trans#ort b) st!mulat!n''lu$ose trans#orter

32 In$rease 'l)$ol)s!s #at*+a)

42 De$rease 'l)$o'enol)s!s #at*+a)

52 In$rease 'l)$o'enes!s #at*+a)

62 De$rease 'lu$oneo'enes!s #at*+a)

12 In$rease TCC a$t!!t)


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11

De"e$t o" $ells o" #an$reas absolutel) la$7 o" !nsul!n leel(

.2 De$rease o" 'lu$ose trans#orts !nto t*e $ells t*at$ause% b) lo+ a$t!!t) o" 'lu$ose trans#orter


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12

b02 De$rease o" 'l)$ol)s!s #at*+a)sa$t!!t)( t*at $ause% b) lo+ a$t!!t) o"t*ree 7!n%s o" 'l)$ol)t!$ en8)mes 9

, Glu$o7!nase :He;o7!nase

, P*os#*o"ru$to7!nase

, P)ruate 7!nase


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13

Glucose

Glucokinase / hexokinase

Glucose-6 P

Fructose-6 P

Phospho fructo kinase

Fructose-1,6 bi P

2 Triose-P

2-Phosphoenol pyruvate ( PEP )

Pyruvate kinase

2-Pyruvate

Note : Glycolysis is oxidation of glucose to form pyruvate or lactate

Insulin

+

+

+


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14

$02 In$rease o" 'l)$o'enol)s!s#at*+a)s a$t!!t) !n t*e l!er( t*at$ause% b) *!'* a$t!!t) o"#*os#*or)lase en8)mes !n t*e l!er


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15

Glycogen

Phosphorylase

Glucose-1 P Insulin

Glucose- P

Glucose- P-ase

Glucose

-

-


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16

Glucagon Insulin

!enylate Phospho !i-

cyclase esterase

TP c"P # "P

Glycogenolysis

Note : Glycogenolysis is glycogen !reakdo"n to form glucose

+

++


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17

%02 De$rease o" 'l)$o'enes!s#at*+a)s a$t!!t)( t*at $ause% b)

lo+ a$t!!t) o" 'l)$o'en s)nt*aseen8)mes


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18

Glucose

Glucose-6 P

Glucose-1 P

$TP

Insulin

$ri!ine !iphosphate

glucose ( $%PG )

Glycogen

Pri&er Glycogen

synthase

Glycogen

Note : Glycogenesis is synthesis of glycogen from glucose

+


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19

e02 In$rease o" 'lu$oneo'enes!s #at*+a)sa$t!!t)( t*at $ause% b) *!'* a$t!!t) o" "our

7!n%s o" 'lu$oneoneo'enet!$ en8)mes 9

, Glu$ose,1 #*os#*atase

, &ru$tose,.(1 b!#*os#*atase

, PEP $arbo;)7!nase , P)ruate $arbo;)lase

Note 9 Glu$oneo'enes!s !s 'lu$ose s)nt*es!s"rom non $arbo*)%rate substrates /la$t!$a$!%s( 'lu$o'en!$ am!no a$!%s( 'l)$erolsan% #ro#!on!$ a$!%s02


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20

Glycogen

Glucose 'eoinase Glucose-6 glucoinase phosphatase Glucose-6 P

Fructose-6 P Phospho Fructose-1,6 *ructoinase biphosphatase Fructose-1,6 bi P

Insulin Insulin

PEP PEP car- Pyruvate boyinase inase

+alo acetate Pyruvate

Pyruvate Pyruvate carboylase +alo acetate

"alate "alate #$$

"itochon!rial &atri

Insulin

+

+

+


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21

"02 De$rease o" TCC a$t!!t)( ma) be$ause% b) %e$rease o" $!trates)nt*ase en8)me a$t!!t)( or la$7 o"

o;aloa$etate


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22

Iso citrate

citrate

%cetyl $o %

α eto glutarate&uccianate

'umarate

(alate

)xalo acetate

$itrate

synthase

Pyruvate

Glucose

FF %mino acids

*ipids

Protein

Insulin

#+$+$

+


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De$rease o" $!trate s)nt*aseen8)mes a$t!!t) or la$7 o"

o;aloa$etate $ause a$et)l CoA $annot be o;!%!8e% !n TCC /%e$rease o"TCC a$t!!t) 0 !n D!abetes Mell!tus2

Note 9

TCC / Tr!$arbo;)l!$ a$!% $)$le 0 !s

o;!%at!on o" a$et)l CoA to "ormCO3( H3O an% ener') ATP2


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24

Change in LipidMetab!i"#


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L!#!% metabol!$ $*an'es( $aus!n' 7eto a$!%os!s(*)#ertr!'l)$er!%em!as an% *)#er$*olesterolem!as

< Ener') #ro%u$t!on "a!lure "rom $arbo*)%rates/'lu$oses0

metabol!sm $ause !n$rease o" l!#ol)s!s "roma%!#ose t!ssues

Insul!n

Hormon sens!t!e l!#ase < Tr!'l)$er!%es &ree"att) a$!%s

Gl $erols


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In$rease o" *ormon sens!t!el!#ase en8)mes a$t!!t) !n DM t)#e.( $ause !n$rease o" l!#ol)s!s "rom

a%!#ose t!ssues an% *!'* bloo%leel o" "ree "att) a$!%s an% +oul%

be ta7en b) t*e t!ssues to beo;!%!8e% / o;!%at!on02


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27

''%

oxidation

%cetyl $o%

#$$

,ydroxy (ethyl Glutaryl $o%

,(G $o% .

$holesterol eton !odies

,ypercholesterolemia. eto acidosis.

0xtra-hepatic tissues

%cetyl $o%

#$$

HMG CoAreductase

HMG CoA lyase


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2$


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29

''% lood.

*iver

*3*

*3* #G.

*ipoprotein lipase

''%

Intestine

0xtra hepatic tissues

Insulin

$hylomicron #G.

Glycerol

+

3ecrease of lipoprotein lipase en4ymes

activity cause hypertriglyceridemia


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30

42 Am!no a$!%s metabol!$ $*an'e

Am!no a$!%s /'lu$o'en!$ a2a0 "rom

%!et /!ntest!ne0 an% "rom #roteol)s!so" #rote!n !n t*e mus$le( enter'lu$oneo'enes!s #at*+a)s !n t*el!er to ma!nta!n bloo% 'lu$ose

$on$entrat!on2


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II+ (0#%)*I$ $,%NG0& IN #5P0-2 3( NI33( .


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CARBOH-DRATE METABOLIC CHANGES

Insul!n leel ma) be normal or sl!'*t!n$rease( but t*ere !s !nsul!n res!stan$e2

T*e !nsul!n re$e#tors $an not "ull)res#on% to !nsul!n( so 'lu$ose trans#orters

be$ome !na$t!e2 Glu$oses $an not enter!nto t*e $ells o" t*e t!ssues es#e$!all)mus$le t!ssues an% $ause *)#er'l)$em!a2

Insul!n res!stan$e !s !n%u$e% b) tumor

ne$ros!s "a$tor /TN&=0 an% a #rote!n $alle%res!st!n t*at #ro%u$e% b) a%!#ose t!ssues2


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L!#!% Metabol!$ C*an'es

L!#o#rote!n l!#ase en8)mes t*at st!mulate%b) !nsul!n( also !na$t!e( so TAG $ontent o"VLDL an% $*)lom!$rons $an not s#l!t !nto"ree "att) a$!% /&&A0 an% 'l)$erols an% $ause

*)#ertr!'l)$er!%em!a2In$rease o" VLDL #ro%u$t!on !n t*e l!er

!s !n%u$e% b) *)#er'l)$em!a an%*)#er!nsul!nem!a2

>etoa$!%os!s rarel) %eelo#( be$ause t*e$ells o" a%!#ose t!ssues st!ll sens!t!e to t*e!nsul!n e?e$t on l!#ol)s!s /!nsul!n !n*!b!tsl!#ol)s!s #at*+a)s !n a%!#ose t!ssues02


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34

Glucagon Insulin

epinephrin etc

%denylate cyclase Phosphodiesterase

%#P c%(P 6 %(P

*ipolysis

++

+


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III2 DIABETES MELLITUS AND PREGNANC-

.2 Metabol!$ C*an'es !n Normal Pre'nant Woman


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N%#a! p%egnan&' i"&ha%a&te%i(ed b')Mi!d *a"ting h'pg!'&e#iaP"tp%andia!

h'pe%g!'&e#iaH'pe%in"+!ine#ia

D+e t pe%iphe%a! in"+!in%e"i"tan&e ,hi&hen"+%e" an ade-+ate"+pp!' * g!+&"e *% thebab'.

Pat*o#*)s!olo')


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H+#an P!a&enta! La&tgen /HPL0P%d+&ed b' "'n&'tit%phb!a"t" *

p!a&enta.A&t" t p%#te !ip!'"i" in&%ea"ed FFA

and t de&%ea"e #ate%na! g!+&"e +ptaeand g!+&negene"i". Anti3in"+!in

E"t%gen and P%ge"te%neInte%*e%e ,ith in"+!in3g!+&"e %e!atin"hip.

In"+!ina"eP!a&enta! p%d+&t that #a' p!a' a #in%

%!e.

Pathph'"i!g'


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T+o reasons t*at $ause metabol!$ $*an'es !n#re'nant +oman

a0 C*an'es o" *ormonal leel !n #re'nan$)es#e$!all) estro'en an% #ro'esteron t*atst!mulate !nsul!n res!stan$e

b0 &etal nee%s "or ener') an%

s)nt*es!s es#e$!all) "rom 'lu$ose( an%am!no a$!%s t*at $ause maternal*)#o'l)$em!a( also la$tate( "ree "att) a$!%san% 7eton bo%!es


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Maternal LDL,$*olesterol !s#re$ursor "or #la$ental stero!%ss)nt*es!s /estro'en an% #ro'esteron0

Pla$enta also #ro%u$e #la$entalla$to'en *ormon /#e#t!%e0 t*atst!mulates l!#ol)s!s !n a%!#ose t!ssues

A"ter "ee%!n'( #re'nant +oman

"alls to "ast!n' state ra#!%l) $ause%b) !n$rease o" 'lu$ose an% am!noa$!% $onsum#t!on b) t*e "etus

56


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40

. Bloo% 'lu$ose( am!no a$!%s @ !nsul!n

leel "alls ra#!%l)( an% on t*e ot*er*an% 'lu$a'on an% #la$entalla$to'en !n$rease t*at $ause!n$rease o" l!#ol)s!s an% 7eto'enes!s#at*+a)s

. C*an'es o" stero!% *ormons an%"uels $ause er) %!$ult to $ontrol

bloo% 'lu$ose !n %!abet!$ #re'nant+oman


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Gestat!onal D!abetes Mell!tus

. A normal +oman be"ore #re'nant( $an%eelo# D!abetes mell!tus +*en s*e !s#re'nant( !ts $alle% 'estat!onal DM

. Usuall) s*e *as a %!abet!$ 'ene t*at

!n*er!te% "rom *er #arents

. E;ess!e "ee%!n' !n #re'nan$) $ausee;$ess!e !n$rease o" bo%) +e!'*t an%!n$rease o" tumor ne$ros!s "a$tor /TN& 0(

an% a #rote!n $alle% res!st!n

. TN& ( res!st!n( estro'en an% #ro'esteron(!n%u$e !nsul!n res!stan$e to %eelo#D!abetes mell!tus !n #re'nant +oman

/'estat!onal DM0


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42

. Gestat!onal DM are 'enerall)

reers!ble a"ter #re'nan$)(a##ro;!matel) 4 6 o" +oman+!t* a *!stor) o" GDM 'o on to%eelo# t)#e,3 DM later !n l!"e(#art!$ularl) !" t*e) are obese2

. Alt*ou'* t*e $ellularme$*an!sms res#ons!ble "or t*e

!nsul!n res!stan$e !n GDM are not"ull) un%erstoo%2


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D!abetes Mell!tus t*at Su#er Im#ose%+!t* Pre'nan$)

. D!abet!$ #re'nant +oman( $auseer) %!$ult to $ontrol bloo%'lu$ose $on$entrat!on

. H!'* leel o" estro'en an%

#ro'esteron +!ll !n$rease !nsul!nres!stan$e an% $ause more seereDM !n %!abet!$ #re'nant +oman

. Maternal *)#er'l)$em!a( $ause*)#er'l)$em!a !n t*e "etus t*at

trans"erre% !a "etal $or%


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&etal *)#er'l)$em!a "etal*)#er!nsul!nem!a s)nt*es!s o"tr!'l)$er!%e !n a%!#ose t!ssueso" t*e "etus an% t*e "etus

be$ome b!''erInsul!n l!7e 'ro+t* "a$tors /IG&0also !n$rease !n t*e "etus so t*e"etus not onl) b!''er( but also

lon'er2 I" t*e "etus +e!'*t moret*an 5( 7'( !t !s $alle% '!antbab)

44


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45

. W*en t*e '!ant bab) !s born(

"etal $or% !s $ut( "etal bloo%'lu$ose leel %e$rease ra#!%l)($aus!n' bab)s *)#o'l)$em!a(be$ause t*ere !s no lon'er 'lu$ose

su##l) "rom maternal bloo%( but*)#er!nsul!nem!a st!ll o$$ur !n t*ebab)

. Glu$ose !n"use or la$tat!on must be'!en as soon as #oss!ble to!n$rease bab)s bloo% 'lu$ose


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A 7i&i+" C'&!e888


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RE&ERENCE

.2 Del!n( T2M2 9 Te;tboo7 o" B!o$*em!str) +!t* Cl!n!$alCorrelat!,

t!ons2 1t* e%!t!on2( 31( #a'e F6 , FF.( 32

A W!le)

Me%!$al Publ!$at!on2

32 Har#er( H2A2 9 Illustrate% B!o$*em!str)2 3t* e%!t!on(31( #a'e

..3 , 342 A Lan'e Me%!$al Boo7

42 Le*n!n'er( A2L2 9 Pr!n$!#les o" B!o$*em!str)2 3n% e%!t!on( .4(

#a'e 5 , 1532 Wort* Publ!s*er2


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Al*am%ul!ll

a*

THAN> -OU


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Sebut7an enam /10 $ara !nsul!nmenurun7an 'lu7osa %ara* Men'a#a #a%a DM t!#e 3 Jaran'

terJa%! 7etoas!%os!sKA#a #erbe%aan *ormon sens!t!e,

l!#ase %en'an l!#o#rote!n l!#aseKA#a )an' men)ebab7an res!stens!

!nsul!n #a%a !bu *am!lKA#a )an' men)ebab7an terJa%!n)a

G!ant Bab)K

UI

metabolic changes in diabetes mellitus.pptx

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