5

HORMON PANKREAS
SEL A ( ALFA) : HORMON GLUKAGON

25%

SEL B (BETA)

70%

: HORMON INSULIN
DAN AMYLIN

SEL D (DELTA) : SOMATOSTATIN

SEL F ( )

< 5%

: POLIPEPTIDA PANKREAS
TRACE HORMONE

AMYLIN
Amylin or Islet Amyloid Polypeptide ( IAPP )
a 37 residu peptide hormone secreted by
pancreatic beta cells at the same time as
insulin

Function :
1. Slow gastric emptying
2. Promote satiety
3. Inhibit secretion of glucagon during
hyperglycemia

PADA

GENETIK

TERTENTU

Amylin = IAPP = Islet Amyloid

Polypeptide
1. Merusak sel beta pankreas
2. Menunjukkan efek antagonis terhadap
hormon insulin pada tingkat reseptor
yaitu menghambat pengikatan insulin
pada reseptornya.

RANTAI A : ADA 1 IKATAN DISULFIDA

30 ASAM AMINO
RANTAI

B : 31 ASAM AMINO
ANTARA RANTAI B DAN C
ADA 2 IKATAN DISULFIDA

RANTAI C : CONECTING PEPTIDE

20 ASAM AMINO

HORMON INSULIN
PRE/ PREPROINSULIN

( 95% ).

INSULIN

PROINSULIN
DAN

PEPTIDA C

PROINSULIN : 1. MASIH PUNYA EFEK

SEBAGAI HORMON
INSULIN : 1-5%.
2. T1/2 LAMA .
3. MENUNJUKKAN
REAKTIVITAS BERSILANG

ALKALI DAN DAN PEREDUKSI :

MEMUTUSKAN IKATAN DISULFIDA
PEMBERIAN PER ORAL AKAN
TERJADI HIDROLISIS INSULIN DI
SALURAN PENCERNAAN
MAKANAN .

FUNGSI PEPTIDA C
1.

MENENTUKAN SEKRESI
INSULIN DARI PANKREAS

2.

MEMBEDAKAN INSULIN
ENDOGEN DAN EKSOGEN

EFEK INSULIN
1.

GLIKOLISIS, GLIKOGENESIS, HMP SHUNT, TCA,

LIPOGENESIS , SINTESIS TG, PROTEIN, VLDL,
KOLESTEROL, TRANSPORT ASAM AMINO,
KARBOHIDRAT,ION, INDUKSI LIPO PROTEIN LIPASE .

2. GLUKONEOGENESIS, GLIKOGENOLISIS, KETOGENESIS,

ENZIM HORMONE SENSITIVE LIPASE
3. DI HATI : MENGHAMBAT KELUARNYA GLUKOSA,
PEMBENTUKAN UREA, c AMP DAN MENINGKATKAN
PENGAMBILAN KALIUM DAN FOSFAT.

PENGAMBILAN

GLUKOSA

PLASMA

GLUCOSE TRANSPORTERS
Glut 1 : otak, ginjal, kolon, plasenta, eritrosit
Glut 2 : hati, sel beta pankreas, usus halus, ginjal
Glut 3 : otak, ginjal, plasenta
Glut 4 : otot jantung dan kerangka, jaringan
adiposa
Glut 5 : usus halus

METABOLISME
INSULIN
TERJADI DI HATI, GINJAL DAN PLASENTA
1.

PROTEASE MENGHIDROLISIS
PEPTIDA PADA RANTAI ALFA

IKATAN
DAN BETA

2.

GLUTATION INSULIN TRANSHIDROGENASE

MEMUTUSKAN IKATAN DISULFIDA

Diabetes Mellitus
Type 1 Diabetes
- cells that produce insulin are
destroyed
- results in insulin dependence
- commonly detected before 30

Type 2 Diabetes
- blood glucose levels rise due to
1) Lack of insulin
production
2) Insufficient insulin
action (resistant cells)
- commonly detected after 40
- effects > 90%
- eventually leads to -cell failure
(resulting in insulin dependence)

Gestational Diabetes
3-5% of pregnant women in the US
develop gestational diabetes

Comparison of Type I and Type II

Diabetes Mellitus
Insert table 19.6

MHC :Major compatibility complex

HbA1c : Glycosylated
or glycated
hemoglobin
HbA1c is a test that measures the
amount of glycosylated hemoglobin in
your blood over the past 3 months
The test gives a good estimate of how
well diabetes is being managed over
time.

THE MAPPING BETWEEN HbA1c

AND
BLOOD GLUCOSE AVERAGE
HbA1c
(%)

Avg. Blood Sugar

(mmol/L)

Avg. Blood Sugar

(mg/dL)

4.5

80

6.7

120

8.3

150

10.0

180

11.6

210

10

13.3

240

11

15.0

270

12

16.7

300

GAMBARAN KLINIK DM
POLIURI, POLIDIPSI, POLIFAGI, BERAT
BADAN MENURUN, PENINGKATAN UREUM
DARAH, TRIGLISERIDA , ASETIL KOA .
PADA DM TIPE I DAPAT TIMBUL
KETOASIDOSIS .
KOLESTEROL DARAH MENINGKAT PADA
DM YANG TIDAK TERKONTROL .

Diabetes Oral
Medications
6 Classes :
Sulfonylureas stimulate cells
Biguanides improves insulins ability to move glucose
Sulfonylureas and biguanide combination
drugs BOTH
Thiazolidinediones cells more sensitive to insulin
Alpha-glycosidase inhibitors Block enzymes that
help digest starches

Meglitinides stimulate cells (dependant upon

glucose conc.)

RESISTENSI

INSULIN

1. GENETIK
2. DIET TINGGI KARBOHIDRAT JANGKA
PANJANG / DIET TINGGI LEMAK
3. DEFISIENSI NUTRISI
dll

: kromium, Zn,

DIABETES
MELLITUS
1. AKROMEGALI
2. SINDROMA / PENYAKIT CUSHING
3. GLUKAGONOMA
4. FEOKROMOSITOMA
5. SOMATOSTATINOMA

SEKUNDER

Obesity/insulin resistance genes

Leptin, Leptin receptor, PC1, POMC, MC4 receptor,
Insulin receptor, PPAR-gamma
Normal Beta Cell

Susceptible Cell

Obesity/insulin resistance

cell dysfunction/
growth

genes
Environment
For example : fat/calories,
physical activity
Increased cell function
Increased cell growth

HNF1, HNF4 ,
Kir6.2, TCF7L2
Mitochondrial
cell dysfunction
cell apoptosis
Impaired glucose tolerance

Normal glucose tolerance

Compensatory hyperinsulinaemia
Type 2 DM

COMPARATION OF INSULIN, IGF I AND IGF II

INSULIN
Other names

Amino acids

51

Source

IGF I

IGF II

somatomedin C

MSA

70

Pancreatic B cells

Level regulated Glucose

by
Plasma level
0,3 2 ng/ml
Plasma binding
protein
Major physiologic role

No
control of metabolism

67

Liver and other tissues diverse

tissues
GH and nutritional
unknown
status
ng/ml range
ng/ml range
Yes
Skeletal and cartilage growth

Yes
Unknown
Embryonic
developtment ?

GLUKAGON

DIBENTUK

PERTAMA KALI SEBAGAI

HORMON INAKTIF DAN MERUPAKAN

HORMON ANTAGONIS TERHADAP
HORMON

INSULIN

FUNGSI
1.

GLUKAGON

MERANGSANG GLUKONEOGENESIS
c AMP MEMACU TRANSKRIPSI GEN
PEPCK

2.

MERANGSANG GLIKOGENOLISIS HATI

3.

MERANGSANG LIPOLISIS , KETOGENESIS,

DAN SEKRESI INSULIN

4. MENGHAMBAT GLIKOLISIS, TCA DAN HMP

EFEK PARAKRIN
GLUKAGON

INSULIN
+
+

POLIPEPTIDA
PANKREAS

SOMATOSTATIN

Insulin affects many organs:

It stimulates skeletal muscle
fibers.
It stimulates liver cells.

amino acids
uptake

glucose
uptake

It acts on fat cells

It inhibits production of
certain enzyme.
In each case, insulin triggers
these effects by binding to the
insulin receptor.

protein
synthesis

glycogen
synthesis

fat
synthesis
enzyme
production

glycogen
breaking

PENGIKATAN INSULIN, IGF I

DAN
IGF II TERHADAP RESEPTOR
RESEPTOR
HORMON

INSULIN

IGF I

IGF II

INSULIN

TINGGI

RENDAH

DIABAIKAN

IGF I
IGF II

MENENGAH TINGGI
DIABAIKAN

RENDAH

MENENGAH
TINGGI

SEKRESI

INSULIN

DIPENGARUHI:
1. GLUKOSA
2. ASAM AMINO, ASAM LEMAK DAN
BADAN
KETON
3. HORMONAL : ADRENALIN, hPL
KORTISOL,ESTROGEN,PROGESTERON
DAN
SOMATOTROPIN

SEKRESI GLUKAGON
DIPENGARUHI
1. GLUKOSA
2.
3.
4.
5.

ASAM AMINO
ASAM LEMAK
SENYAWA KETON
HORMON SALURAN PENCERNAAN
MAKANAN.
6. NEUROTRANSMITTER

Major compatibility
complex