UPN-DM-2 09-copy

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TNF RESISTENSI INSULINRESISTENSI INSULIN HIPERINSULINEMIA Toleransi Glukosa Normal

GANGGUAN FUNGSI SEL

RESISTENSI INSULIN DEFEK SEKRESI INSULIN TGT

1.Adapted from Diabetes 1996;45:1661 2.Evans JL. Diabetes 2003

Evans JL. Diabetes 2003

30% 50%

Type 2 diabetes IGT

50% 70-100%

70%100%

Impaired glucose metabolismNormal glucose metabolism

150%100%

Diabetes Obes Metab 1999; 1(1): S1

30% 50%MGT TGT DM-2

50% 70-100%

70%100%

150%100%Diabetes Obes Metab 1999; 1(1): S1

go

Stages of type 2 Diabetes in relationship to 100 -cell function

75Beta cell function (%)

back

50

IGT25

Postprandial Hyperglycemia

Type 2 Diabetes Phase 1

Type 2 Diabetes Phase 22 6 10

Type 2 Diabetes Phase 3

0- 12 - 10 -6 -2 0 14

Years from diagnosis hypoX-jsk-7-99

GLUT-2 Glucose

Glucokinase

Glucose Metabolism

G-6-P K+ATP

Signal (S) Secretory Granules

ATP ___ ADP

Depolarization

Insulin Secretion

Ca++

Insulin secretion profiles in Type 2 diabetic patients and healthy people800

Insulin secretion (pmol/min)

700 600 500 400 300 200

Healthy people Type 2 diabetic patients

1006am 10am 2pm 6pm 10pm 2am 6am

TimePolonsky KS. Et al., 1988

Patterns of Insulin Response to IV Glucose: Non-Diabetic and Diabetic IndividualsIV Glucose StimulusInsulin Secretion-10 -5 0 5

Phase10 15 20 25 30 35

1ST

Phase40 45 50 55 60 65 70 75 80

2ND

Non-Diabetic

85 9

Insulin Secretion

Type 2 Diabetes

-10 -5

0

5

10

15 20 25 30 35 40 45 50 55 60

65 70 75 80 85 9

Time (minutes)

GLUT-2 Glucose

Glucokinase

Glucose Metabolism

G-6-P K+ATP

Signal (S) Secretory Granules

ATP ___ ADP

Depolarization

Insulin Secretion

Ca++

back

SIGNAL

Insulin sensitif

Resistensi Insulin

back

glukosa

metabolisme

subkutis

ektopikviseral hati jantung otot

CRP TNF

Resistensi insulin

TNF

Insulin sensitifTNF-R autofosforilasi tirosin

Ins-R

IRS

PI3KKahn, Atlas of diabetes 2000Evans JL. Diabetes 2003

TNF

Resistensi InsulinTNF-R

Ins-R

Kinase serin

IRS

PI3KKahn, Atlas of diabetes 2000Evans JL. Diabetes 2003

back

NORMAL RESISTENSI INSULIN

**

*

*

Khan CR. Atlas of Diabetes 2000

Translokasi

Transkripsi

Insulin

Glucose

Insulin receptor

Synthesis GLUT 4 PPARg+ RXR

mRNA

PPRE

transcription

promoter

Coding reg

Modified from Howard L. Foyt et al. Thiazolidinediones. Diabetes Mellitus: a Fundamental and Clinical Text, 2nd Ed.

Insulin resistanceInsulin

Glucose

Insulin receptor

X

X Synthesis GLUT 4PPARg +RXR mRNA

PPRE

transcription

promoter

Coding reg

Modified from Howard L. Foyt et al. Thiazolidinediones. Diabetes Mellitus: a Fundamental and Clinical Text, 2nd Ed.

Shepherd and Kahn. NEJM 1999; 341:248-257

back

INSULINGLIKOGENGLIKOGEN SINTASE

back

Produksi Glukosa Hati

Insulin sensitive (normal)Insulin

FFA + gliserolHSL

Insulin receptor

+ -

TG

PPARg +RXR

Gi+

Fat CellsCatecholamines PGEs Adenosine

Modified from Diabetes, Obesity and Metabolism, 3 (Supp.1), 2001, S11-S19.

Obesity & Insulin resistanceInsulin

FFA + gliserolHSL

Insulin receptor

+ -

-

TNF-PPARg +RXR

-

TG

Gi+

Fat CellsCatecholamines PGEs Adenosine

Modified from Diabetes, Obesity and Metabolism, 3 (Supp.1), 2001, S11-S19.

FFA

DM tipe-2

Diabetes Care, 1999; 22:562

Insulin Resistance: Associated ConditionsType 2 diabetes

AtherosclerosisDyslipidemia Decreased fibrinolytic activity Insulin Resistance

Impaired glucose tolerance Hypertension

Obesity (central)

Acanthosis nigricans

Polycystic ovary disease Hyperuricemia