What two classes of glucose carrier transfers glucose across the plasma membrane?
Sodium-coupled glucose transporters
Facilitative glucose transporters
Where is sodium-dependent glucose cotransporter expressed?
In absorptive and reabsorptive epithelia such as intestine and kidney.
How is glucose transport from the lumen of the intestine or nephrons?
They have to actively uptake glucose against its concentration gradient.
By coupling sodium uptake with glucose
Structure of the SGLT1?
14 TM domains.
Mutations affecting the transporter.
Loss the capacity to absorb glucose
What is the conditions glucose-galactose malabsorption?
Glucose-galactose malabsorption is a condition in which the cells lining the intestine cannot take in the sugars glucose and galactose, which prevents proper digestion of these molecules and larger molecules made from them.
SGLT1 transport mechanism?
Bind to sodium ion.
Sugar then binds and thus a confirmational change.
New site present.
Sugar unbinds and thus so does sodium.
Causing a confirmational change.
How is glucose absorbed across the intestinal membrane?
Gut lumen to cells by SGLT1
From cells into blood: GLUT2
Na:K symporter used to generate ATP
Faciliative glucose transporters
Integral membrane protein
Present on the surface of all cell membranes.
Transports glucose down its gradient.
The 3 classes on facilitative GLUT family?
Class 1 GLUT transport includes?
High affinity binding protein: GLUT 1, 3 4.
Low-affinity binding protein: GLUT2.
Class 2 GLUT transport includes?
Very low affinity: GLUT 5, 7, 9, 11.
Myoinositol transporter HMIT1
Class 3 GLUT transport includes?
GLUT 6, 8, 10, 12
Tissues involved in absorption, reabsorption and glucose sensing
GLUT 2 transporter?
Role in sensing glucose conc. in islets.
Kidney, pancreatic beta cells, liver
GLUT 3 transporters?
Placenta so the child will always receive the glucose it requires even if the mother is fasting
Skeletal and cardiac muscle, adipose tissues
Responsible for mediating insulin-sensitive glucose transport.
Specifically binds to facilitative glucose transporters
Inhibits cell functions such as division and movement
Binds to the cytoplasmic domain of the transporter
What does insulin do to the glucose transporters?
Stimulates the movement or translocation of glucose transporters from the intracellular membrane to the plasma membrane.
Use of green fluorescent protein in testing that insulin effects the translocation of glut4?
its a gene
Chrimetic protein can be produced of GLUT4.
Insulin comes in: can see the GLUT4 vesicles (as they are green) translocating to the plasma membrane
Insulin post-receptor signalling?
Insulin binds to the tyrosine kinase receptor at the alpha subunit.
Can activate the signalling pathways by the activation of: P13-kinase, PKB, MAP kinase, p70S6 kinase.
Important for glucose transport, glycogen synthesis, protein synthesis etc.
Action of insulin on muscle?
Increase of glucose uptake by increasing GLUT4 at cell surface.
Increase glucose effects: glucogen synthesis, glycolysis.
Increase amino acid uptake.
Increase protein synthesis.
Regulation of skeletal muscle glucose uptake during exercise?
What is glucose phosphorylated into and how is this important?
GLUT4 allows transport of glucose
Glucose phosphorylated by hexokinase (HK) to form G6P.
G6P enters glycolysis
Maitains the concentration gradient for glucose to passively enter the cell.
As it cannot diffuse out of the cell.
Why is G6P and HK important for type 2 dibaetes?
In type 2 diabetes: stimulation of flucose uptake is impaired in muscle..
However, exercise still stimualtes glucose uptake despite reduction in insulin-stimulated glucose
Name the 6 methods to study exercise and muscle contraction?
Biopsies (From humans)
How does insulin and exercise differ when enhancing muscle glucose uptake
Exercise stimulates AMPK (kinase)
Senses the reduction in cellular levels.
Becomes activated when levels become too low.
Oral antidiabetic drug
stimualtes the GLUT4 translocation.
What is the metabolic effects of AICAR and Metformin?
Inhibit hepatic glucose production
Stimulate muslce glucose uptake
Increase Lactic acid production
GLUT class receptor characteristics?
12 transmembrane domains
NH2 and COOH are facing the cytoplasm face.