Beruflich Dokumente
Kultur Dokumente
ATP
NIMGU
Glucose
CO2 + H2O
Central Nervous System
Glucose
8
7
Insulin
25
Glucose
5
4
08
12
16
20
24
04
(+) Insulin
G6P
GLUT-4
(+)
Insulin
2) Insulin Increase
-Glycogenolysis
-Lipogenesis
-utilization of carbohydrates a fuel
Glycogen
(+) Insulin
08
(+) Insulin
(+) GH
(+) IGF-1
Insulin (+)
NIMGU
Insulin (+)
(+)Catecholamines
GLUT-4
Glycolysis
Insulin (+)
Pyruvate
CO2 + ATP
Lactate
Gluconeogenesis
Protein
Lactate
(+) Glucocorticoids
Insulin, GH, IGF-1
-Increased entry of AA into the cell
-Increase protein synthesis
Liver
*Glucocorticoids enhance
proteolysis
GLUT-2
Regulated Pathway
> 95% Insulin > Proinsulin
exocytosis
++[K+]
+ ATP
Glycolysis
Constitutive Pathway
< 5%, Proinsulin > Insulin
Insulin
Ca++
TGN
Beta Cell
n
ati
Kir6.2
(Inward-rectifing potassium channel)
*Inhibit: ATP + ADP
*Activate: PIP2, Fatty Acid Metabolites
Glucose Glucokinase
ProInsulin
Pre-Pro-Insulin
rER
Insulin Secretion
1) Eat >>> blood [Glc]
2) Glc enters B-Cell via GLUT-2
3) Glc metabolism increase ATP:ADP ratio
4) (+) ATP:ADP ratio inhibits Kir6.2/SUR1 potassium channel
5) Increase in intracellular K+ depolarizes cell
6) depolarization opens V-gates Ca++ channels
7) increase intacellular [Ca] activates PLC
8) PLC > IP3 + DAG
9) IP3 > ER > further increase in [Ca]
10) increase in [Ca] >>> vesicle fusion + Insulin exocytosis
Sympathetic
t
tos
ma
So
Depolarization
Parasympathetic
Insulin +
C-Peptide
G6P
SUR-1
*Inhibited by Sulfonyl-ureas
*Activated by: Diazoxide, Mg-ATP, Mg-ADP
Randal Cycle
-Low blood Glucose
= low insulin
Glucose
(+) Insulin
(+) GH
(+) IGF-1
AA (cytoplasm)
Triglycerides
+ NEFA
Glycogen
CO2 (OXPHOS)
(-) Insulin
(+)
Insulin
Triglyceride
Randal Cycle
-Rate of Glucose & Fatty Acid utilization in Muscle are
inversely related
-Low Insulin State (fasting) Fatty Acid Oxidation is favored
3) Insulin Inhibits
utilization of AA for fuel
AA (plasma)
Glycerol
Adipose Tissue
Fat
50
Meals
Insulin (+)
Glucose
on
Cortisol
NIMGU
Glu
cag
Epinephrine
NEFA
uli
n
Glucagon
Insulin (+)
Ins
Insulin
Blo
od
Flo
w
Hormone
Glucagon
Somatostatin
Insulin Processing
1) Insulin is Synthsized a Pre-Proinsulin
2) Pre-ProInsulin is processed to Pro-insulin before TGN (@ rER)
(Pro-insulin = A~c~B)
Endopeptidase cleave C
@ Lys(64)~Arg(65)
@ Arg(31)~Arg(32)
3) Mature Insulin is in Granules
To Portal Vein