BIOC/DENT/PHCY 230
LECTURE 7
Fed state characterised by:
 increased plasma concentration of fuel molecules
 increased rate of uptake of fuel molecules from
plasma
 increased storage of fuel molecules in appropriate
tissues
 release of specific hormones to regulate fed state
metabolism
Glucose metabolism in the fed state
 regulated by insulin
glucose uptake in muscle and adipose tissue
glycogen synthesis
gluconeogenesis
glycogenolysis
Movement of glucose is regulated by
specific transporters
Glucose transporters may:
 be insulin dependent or independent
 have a high or low affinity for glucose
 be ubiquitous or restricted in tissue distribution
 move glucose up or down its concentration
gradient
high affinity
low affinity
Model mechanism for glucose transport
Glucose uptake from small intestine
 glucose is moved across the enterocyte cell membrane by
co-transport with Na+
glc
glc
SGLT1
glc
Na+
glc
enterocyte
intestinal lumen
GLUT2 transports glucose out
of the enterocyte
glc
glc
glc
GLUT2
glc
enterocyte
Insulin independent
hepatic portal vein
Low affinity, high capacity (KM 7-20mM)
Fructose has its own transporter
fru
fru
fru
GLUT5
GLUT2
fru
fru
enterocyte
 insulin independent
hepatic portal vein
Stimulation of insulin secretion
 there are many stimuli that can promote insulin
secretion
 pancreatic b-cells use GLUT1 and GLUT2 to sense blood
glucose levels
 GLUT1 has a KM around physiological plasma [glucose]
 GLUT2 has a higher KM
 insulin secretion is stimulated by glucose concentrations
around 8mM
GLUT4 is an insulin sensitive transporter
 GLUT4 cycles between
the plasma membrane and
intracellular vesicles
 insulin stimulates the
translocation of GLUT4 to
the plasma membrane
 insulin increases the
rate of transport by
GLUT4
Glucose uptake by the brain
KM ~ plasma [glucose]
 low KM
glc
 regulates
entry into
neurons
GLUT1
blood brain
barrier
glc
GLUT3
neuronal
cell membrane
glc
Properties of glucose transporters
Glycogen
 glycogen is the storage body for glucose
 main stores are in skeletal muscle and liver
 provides a reserve of glucose that can be
mobilised between feeding or during exercise
 structure: a branched chain polymer
 synthesis occurs when glucose is plentiful in the
fed state and is stimulated by insulin
Glycogen biosynthesis
 straight chain glucose polymers are
synthesised by glycogen synthase
 glycogen synthase can’t join together free
glucose units
 requires a primer to initiate synthesis
 glycogenin is a protein, on which this primer is
synthesised
 glucose is added to glycogenin in the form of
UDP-glucose
UDPG synthesis
Synthesis of glycogen primer on glycogenin
tyr
glycogenin
Glycogen synthase extends this primer
Activation of glucose
Glycogen has a branched structure
branching enzyme
(amylo-(1,4 1,6)-transglycosylase)
Glycogen Storage Diseases
Glycogen Synthase Deficiency (Liver)
 glycogen synthesis slower; poor glycogen reserve
 symptoms:fasted state - hypoglycemia
fed state - hyperglycemia
glucose intolerance
 treatment: avoid long periods of fasting; diet
Branching enzyme deficiency:
 abnormal glycogen structure...cell damage
 consequences: liver cirrhosis, neuromuscular
defects, death within 3 years
The take home message
 glucose metabolism in the fed state is
characterised by glucose uptake and storage
 insulin is a key mediator of glucose metabolism in
the fed state
 a variety of glucose transporters mediate glucose
uptake depending on tissue requirements
 glycogen is the storage body for glucose
 the highly branched structure of glycogen
improves the efficiency of glucose mobilisation
 defects in glycogen synthesis can cause disease