Effects of insulin on muscle

Question 1

What two classes of glucose carrier transfers glucose across the plasma membrane?

Answer 1

Sodium-coupled glucose transporters

Facilitative glucose transporters

Question 2

Where is sodium-dependent glucose cotransporter expressed?

Answer 2

In absorptive and reabsorptive epithelia such as intestine and kidney.

Question 3

How is glucose transport from the lumen of the intestine or nephrons?

Answer 3

They have to actively uptake glucose against its concentration gradient.

By coupling sodium uptake with glucose

Question 4

Structure of the SGLT1?

Answer 4

14 TM domains.

Mutations affecting the transporter.

Loss the capacity to absorb glucose

Question 5

What is the conditions glucose-galactose malabsorption?

Answer 5

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.

Question 6

SGLT1 transport mechanism?

Answer 6

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.

Question 7

How is glucose absorbed across the intestinal membrane?

Answer 7

Gut lumen to cells by SGLT1

From cells into blood: GLUT2

Na:K symporter used to generate ATP

Question 8

Faciliative glucose transporters

Answer 8

Integral membrane protein

Present on the surface of all cell membranes.

Transports glucose down its gradient.

Bi-directionally

Question 9

The 3 classes on facilitative GLUT family?

Answer 9

Class 1->3

7TM domain.

Question 10

Class 1 GLUT transport includes?

Answer 10

High affinity binding protein: GLUT 1, 3 4.

Low-affinity binding protein: GLUT2.

Question 11

Class 2 GLUT transport includes?

Answer 11

Very low affinity: GLUT 5, 7, 9, 11.

Myoinositol transporter HMIT1

Question 12

Class 3 GLUT transport includes?

Answer 12

GLUT 6, 8, 10, 12

Question 13

GLUT1 transporter?

Answer 13

Low Km

High affinity.

Garage door.

Tissues involved in absorption, reabsorption and glucose sensing

Question 14

GLUT 2 transporter?

Answer 14

High Km

Low affinity.

Role in sensing glucose conc. in islets.

Kidney, pancreatic beta cells, liver

Question 15

GLUT 3 transporters?

Answer 15

High affinity

Placenta so the child will always receive the glucose it requires even if the mother is fasting

Question 16

GLUT4 transporter?

Answer 16

Insulin responsive

Skeletal and cardiac muscle, adipose tissues

Responsible for mediating insulin-sensitive glucose transport.

Question 17

Cytochlasin B?

Answer 17

Fungal metabolite.

Specifically binds to facilitative glucose transporters

Non-competitive.

Inhibits cell functions such as division and movement

Binds to the cytoplasmic domain of the transporter

Question 18

What does insulin do to the glucose transporters?

Answer 18

Stimulates the movement or translocation of glucose transporters from the intracellular membrane to the plasma membrane.

GLUT4

Question 19

Use of green fluorescent protein in testing that insulin effects the translocation of glut4?

Answer 19

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

Question 20

Insulin post-receptor signalling?

Answer 20

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.

Question 21

Insulin Pathway

Answer 21

Question 22

Action of insulin on muscle?

Answer 22

Increase of glucose uptake by increasing GLUT4 at cell surface.

Increase glucose effects: glucogen synthesis, glycolysis.

Increase amino acid uptake.

Increase protein synthesis.

Question 23

Regulation of skeletal muscle glucose uptake during exercise?

Answer 23

Regulated by:

Glucose supply

Glucose transport

Glucose phosphorylation

Question 24

What is glucose phosphorylated into and how is this important?

Answer 24

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.

Question 25

Why is G6P and HK important for type 2 dibaetes?

Answer 25

In type 2 diabetes: stimulation of flucose uptake is impaired in muscle..

However, exercise still stimualtes glucose uptake despite reduction in insulin-stimulated glucose

Question 26

Name the 6 methods to study exercise and muscle contraction?

Answer 26

Cultured myotubes

Electrical stimulation

Nerve stimulation

Treadmill

Wheel running

Biopsies (From humans)

Question 27

How does insulin and exercise differ when enhancing muscle glucose uptake

Answer 27

Exercise stimulates AMPK (kinase)

Senses the reduction in cellular levels.

Becomes activated when levels become too low.

Question 28

Metformin?

Answer 28

Oral antidiabetic drug

Activates AMPK.

stimualtes the GLUT4 translocation.

Question 29

AICAR?

Answer 29

another drug

resembles AMPK

Question 30

What is the metabolic effects of AICAR and Metformin?

Answer 30

Inhibit hepatic glucose production

Stimulate muslce glucose uptake

Increase Lactic acid production

Question 31

GLUT class receptor characteristics?

Answer 31

12 transmembrane domains

NH2 and COOH are facing the cytoplasm face.