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GLUT.pptx
1. Jimma University
Institute of Health Sciences
Department of Biochemistry
Course Title: Cell biology
Seminal Presentation on- Glucose transporter
By;- Getahun Alega…RM0877/15-0
Submitted to:-Dr.Zerihun
2. Objective
• At the end of this presentation the Learner will be able to:
– To understand the different mechanism of glucose transport across cellular
membranes.
– To define and classify GLUT transporters.
– To differentiate the different GLUT transporters .
– To discus the regulation of glucose transport.
3. Introduction
Glucose is a key energy source for most living cells.
Due to its polar nature and large size, glucose molecules cannot traverse the lipid
membrane of the cell by simple diffusion.
Instead, the entry of glucose molecules into the cells is effected by a large family
of structurally related transport proteins known as glucose transporters.
Two main types of glucose transporters have been identified, namely,
sodium–glucose linked transporters (SGLTs) and
facilitated diffusion glucose transporters (GLUTs)
4. Structure of SGLTs and GLUTs.
SGLT comprises 14 transmembrane helices of which both the COOH and
NH2 terminals face the extracellular space.
All members of the SGLT family are 60- to 80-kDa proteins containing 580–718
amino acids.
GLUTs are proteins comprising 12 membrane-spanning regions with
intracellularly located amino and carboxyl terminals.
The amino acid sequence of GLUT proteins has been found to show 28–65 %
identity against GLUT 1.
5. Glucose transporters
Glucose transporters are integral membrane glycoproteins with;-
molecular masses of about 50,000 daltons, and
each has 12 membrane- spanning α-helical domains.
Transporter exposes a single substrate binding site toward either the outside or the inside of
the cell.
Binding of glucose to one site provokes ;-
a conformational change associated with transport,
and releases glucose to the other side of the membrane.
6. Class of GLUT
Glucose homeostasis within the body is mainly maintained by the various
members of the GLUT protein family comprising 14 isoforms.
Within the GLUT protein family,
Three different subclasses can be distinguished based on primary sequence
comparisons:
class I comprises the classical transporters GLUT1–4 including the gene
duplication of GLUT3, which is GLUT14;
class II contains the ‘‘odd’’ isoforms GLUT5, 7, 9, and 11 and
class III contains the ‘‘even’’ isoforms GLUT6, 8, 10, 12 and the proton
driven myoinositol transporter HMIT (GLUT13).
7. GLUT1
RBC, placenta, brain, retina, colon, kidneys.
• Low Km (35-90 mg/dl), high affinity
• Liver, adipose tissue, muscle cell also expresses GLUT1 during
starvation.
• Dysfunction can cause hypoglycorrachia (low CSF glucose), but
normal blood glucose.
8. GLUT2
Liver, intestine kidneys, beta cells of pancreas.
• High Km (about 450 mg/dl) and high Vmax .
• Facilitated diffusion and bidirectional.
suited for sensing high glucose level and release of insulin.
So this enables pancreas to monitor glucose level and adjust rate of insulin secretion.
• In humans, an inactivating mutation of GLUT2 is present in Fanconi-Bickel syndrome.
9. GLUT3
brain, placenta, kidneys.
• Lowest Km
• Facilitated diffusion of glucose in brain
• Liver, adipose tissue, muscle cell also expresses GLUT3 during starvation.
• GLUT3 is most known for its specific expression in neurons and has
originally been designated as the neuronal GLUT.
• Has higher affinity for glucose than GLUT1, -2 and -4.
10. GLUT4
Skeletal muscle, adipocytes, heart
• Low Km (36-90 mg/dl)
• Under the control of insulin.
• Insulin promotes the translocation of intracellular GLUT4 molecules to the cell surface
and thus increases glucose uptake.
In Type 2 diabetes mellitus membrane GLUT4 is reduced leading to insulin resistance
in muscle and fat cells.
In diabetes, entry of glucose into muscle is only half of normal cells.
11. GLUT5
GLUT5 is a fructose transporter expressed on the apical border of enterocytes in
the small intestine.
• GLUT5 is also expressed in skeletal muscle, testis, kidney, fat tissue (adipocytes),
and brain.
• Facilitated diffusion of fructose
• Fructose malabsorption or Dietary Fructose Intolerance is a dietary disability of the
small intestine, where the amount of fructose carrier in enterocytes is deficient.
12. GLUT6 and GLUT7
GLUT6 - does not mediate glucose uptake and is localized on lysosomal
membranes.
We conclude that GLUT6 is a lysosomal transporter that is regulated by
inflammatory stimuli and modulates inflammatory responses by affecting
the metabolic shift in macrophages.
• GLUT7 - is primarily expressed in the small intestine and colon, transport
glucose from ER to cytoplasm.
13. GLUT8, GLUT9 and GLUT10
GLUT8 - is expressed mostly in neurons and testis.
being expressed at high levels in testes and in the acrosomal part of spermatozoa.
Furthermore, GLUT8 appears to play an important role in the energy metabolism
of sperm cells
• GLUT9, which has multiple isoforms in humans is expressed mainly in the
proximal tubule of the kidney and in the liver and placenta.
GLUT10 - Located in cells of tissues—for example, skeletal muscle, heart, lung,
brain, placenta, kidney, liver and pancreas.
14. GLUT11, GLUT12 and GLUT13
GLUT11 - facilitates the transport of both glucose and fructose.
• GLUT12 - is expressed in cells of adipose tissue, small intestine,
skeletal muscle and placenta.
• GLUT13 - is expressed in adipose tissue and kidney cells.
It is also predominantly expressed in the brain, especially in the
hippocampus, hypothalamus, cerebellum and brain stem.
15. SGLUT
Sodium-dependent glucose cotransporters (or sodium glucose linked transporter,
SGLT) are a family of glucose transporter found in the intestinal mucosa (enterocytes)
of the small intestine (SGLT1) and the proximal tubule of the nephron.
• A membrane bound carrier protein is involved which carries glucose along with sodium.
• The transporter in intestine is SGluT1 and the transporter in kidney is SGluT2.
The first one is involved in glucose-galactose malabsorption and latter is defective in
congenital renal glycosuria.
16. Regulation of Glucose Transport
Glucose enters cells by facilitated diffusion.
GLUT transporters are thought to be involved in Na+-independent facilitated
diffusion of glucose (co-transport system) into cells.
Insulin stimulates glucose transport by promoting translocation of intracellular
vesicles;-
that contain the GLUT4 and GLUT1 glucose transporters to the plasma
membrane.
This effect is reversible.
17. Insulin interacts with the
receptors
Glucose transporters stored in
the vesicles move to the surface
Fuse with the PM
Increase in the no. of glucose
transporter in the PM
Inflow of glucose
18. Cont….
Glucose transport, the rate limiting step in glucose metabolism in
skeletal muscle,
is mediated by insulin-sensitive glucose transporter 4 (GLUT4) and
can be activated in skeletal muscle by two separate and distinct
signaling pathways:
one stimulated by insulin and
the second by muscle contractions.
19. Cont….
the importance of GLUT4 regulation for overall glucose
homeostasis.
In addition to its function in muscle and fat, GLUT4 acts in the
brain and other tissues.
In skeletal muscle, GLUT4 is translocated to the cell surface in
response to contraction as well as insulin stimulation, and ischemia
causes GLUT4 translocation in the heart
Skeletal muscle accounts for the bulk of glucose removal from the
blood.
