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INSULIN
SINDROMA
PROTEIN
Ref. : Peter H. Bennett; Definition, Diagnosis, and Classification of Diabetes Mellitus and Impaired Glucose Tolerance; Joslins Diabetes Mellitus; 13th ed.; 1994; hal. 193
Diagnosis DM
140
200
M G T
TGT
100
126
D M
Klasifikasi
DM DM DM DM tipe-1 tipe-2 tipe Gestasional tipe lain
Postprandial Glucose
Fasting Glucose
10
15
20
25
30
Years of Diabetes
160
140 120 100 Normoglycemia IGT
3
Harris MI Diabetes Care 1993; 16:
Insulin secretion
DM-2 TGT MGT Normal 50% 70-100% 150% 100%
< 100
< 100
< 140
< 140
Insulin secretion
50% 70-100% 150% 100%
75
Beta cell function (%)
50
IGT
25
Postprandial Hyperglycemia
0
- 12 - 10 -6 -2 0 14
RESISTENSI INSULIN
SEKRESI INSULIN
GLUKOSA DARAH
Topik
FISIOLOGI TRANSPORT GLUKOSA* TRANSPORT GLUKOSA PD DM-2* FISIOLOGI SEKRESI INSULIN* SEKRESI INSULIN PADA DM-2* RESISTENSI INSULIN*
ekstra sel
intra sel
glukosa
hidrofilik
ekstra sel
intra sel
glukosa
hidrofilik
GLUCOSE TRANSPORTER (GLUT) 1 - 7
pankreas/hepar
GLUT-2
Insulin dependent
Insulin independent
GLUCOSE TRANSPORTER (GLUT) 1 - 7
ekstra sel
insulin
GLUT-4
Glukosa
Vesikel GLUT 4
ekstra sel
insulin
GLUT-4
Insulin
Glucose
Insulin receptor
mRNA
PPRE
transcription
promoter
Coding reg
Modified from Howard L. Foyt et al. Thiazolidinediones. Diabetes Mellitus: a Fundamental and Clinical Text, 2nd Ed.
intra sel
ekstra sel insulin
reseptor insulin
insulin
insulin
GLUT-4
FISIOLOGI
intra sel
ekstra sel insulin
reseptor insulin
insulin
insulin
GLUT-4
DM-2
Glukosa
Vesikel GLUT 4
Glucose
G-6-P K+ATP
Metabolism
Signal (S) Secretory Granules ATP ADP
Depolarization
Ca++
Insulin Secretion
Rorsman,Renstrom 2003
Phase
10 15 20 25 30 35
1ST
Phase
40 45 50 55 60 65 70 75 80
2ND
Non-Diabetic
85 9
Insulin Secretion
Type 2 Diabetes
-10 -5
10
15 20 25 30 35 40 45 50 55 60
65 70 75 80 85 9
Time
100
6am
Polonsky KS. Et al., 1988
10am
2pm
6pm
10pm
2am
6am
Time
Insulin sensitif
Resistensi Insulin
TNF
3
*
GO
FFA + gliserol
HSL
Insulin receptor
+ -
TG
PPARg +RXR
Gi
+
Fat Cells
Catecholamines PGEs Adenosine
FFA + gliserol
HSL
Insulin receptor
+ -
TNF-
PPARg +RXR
TG
Gi
+
Fat Cells
Catecholamines PGEs Adenosine
back
Evans JL. Diabetes 2003
TNF IL-6
TG* Glukoneogenesis*
Hak, Lemieux ATVB 1999
TNF
LPL
HSL
IL-6
TG
FFA
back
Hak, Lemieux ATVB 1999
INSULIN
GLIKOGEN
GLIKOGEN SINTASE
back back
TNF
TNF-R
Ins-R
Kinase serin
IRS
PI3K
Kahn, Atlas of diabetes 2000
Evans JL. Diabetes 2003
FFA
Translokasi
Transkripsi
Insulin resistance
Insulin
Glucose
Insulin receptor
X Synthesis GLUT 4
PPARg +RXR mRNA
PPRE
transcription
promoter
Coding reg
back
Modified from Howard L. Foyt et al. Thiazolidinediones. Diabetes Mellitus: a Fundamental and Clinical Text, 2nd Ed.
INSULIN
GLIKOGEN
GLIKOGEN SINTASE
GLUT-4
HGP
INSULIN
GLIKOGEN
GLIKOGEN SINTASE
GLUT-4
HGP
Insulin Resistance Hyperinsulinemia Normal Glucose Tolerance Insulin Resistance Declining Insulin Levels Impaired Glucose Tolerance
Type 2 Diabetes
Adapted from Diabetes 1996;45:1661
FFA + gliserol
HSL
Insulin receptor
+ -
TNF-
PPARg +RXR
Pio
TG
Gi
+
Fat Cells
Catecholamines PGEs Adenosine