Acute regulation of glucose

Question 1

Within what range must plasma [glucose] remain?

Answer 1

3-10 mM

Question 2

Which of the glucose transporters (SGLT or GLUT) require Na^₊?

Answer 2

SGLT

Question 3

Which of the GLUT transporters is insulin responsive?

Answer 3

GLUT-4

Question 4

What are the most abundant cells in the islets of Langerhans, what do they secrete and where are they located?

Answer 4

Beta cells - centrally located. Insulin.

Question 5

Where are alpha cells found and what do they secrete?

Answer 5

At the periphery - secreting glucagon.

Question 6

What do delta cells secrete?

Answer 6

Somatostatin

Question 7

What do F cells secrete?

Answer 7

Pancreatic polypeptide.

Question 8

How do beta cells sense glucose (and AA)?

Answer 8

By using it to make ATP.

Question 9

Which transporter does glucose use to enter beta cells?

Answer 9

GLUT-2 - insulin insensitive and low affinity

Question 10

What is the effect of a rising [ATP] within the beta cell?

Answer 10

Closes K⁺ATP channel depolarising the membrane. Ca²⁺ influx and CICR induce exocytosis of insulin.

Question 11

Do you get a larger insulin response to oral or IV glucose?

Answer 11

Oral

Question 12

What sort of insulin response is elicited by IV glucose?

Answer 12

Biphasic

Question 13

What other pathways may increase insulin exocytosis?

Answer 13

Other secretagogues (incretins) act via cAMP or PLC pathways.

Question 14

Which G protein pathway antagonises the pathway?

Answer 14

Gi

Question 15

What is the effect of the parasympathetic nervous system on secretion?

Answer 15

Increases

Question 16

What is the effect of the sympathetic nervous system on insulin secretion?

Answer 16

Inhibits.

Question 17

How is insulin produced?

Answer 17

Prohormone

Question 18

How is insulin processed in the Golgi?

Answer 18

Cleaved to give A and B chains which are linked by disulphide bridges. Inactive C-peptide also produced.

Question 19

How is C-peptide useful?

Answer 19

As a marker of endogenous insulin production.

Question 20

What kind of receptor is the insulin receptor?

Answer 20

Tyrosine kinase - TK domains phosphorylate each other and nearby proteins - insulin receptor substrates.

Question 21

What are the two main pathways of insulin receptor signalling?

Answer 21

PI3K and PKB phophorylate proteins altering activity and inserting (GLUT 4)

MAPK pathway alters gene expression.

Question 22

What are the effects of insulin on the liver?

Answer 22

Glycogen storage and VLDL production increase while gluconeogenesis and ketone body production are inhibited. No GLUT-4 involved.

Question 23

What are the effects of insulin on the muscles?

Answer 23

GLUT-4 inserted and favours the use of glucose. Glycogen, triglyceride and protein synthesis increase.

Exercise via adrenaline also induces GLUT-4 and synergises with insulin.

LPL exported to endothelium where it extracts free fatty acids (FFA) from VLDL.

Question 24

What are the effects of insulin on fat?

Answer 24

GLUT-4 inserted and favours uptake of glucose. Trigylceride storage increased. Export of FFA and glycerol reduced.

Question 25

What drives the release of glucagon from alpha cells?

Answer 25

Amino acids.

Question 26

What antagonises the release of glucagon from alpha cells?

Answer 26

Glucose

Question 27

What happens to glucagon in L cells?

Answer 27

Converted to GLP1 - potent incretin.

Question 28

What are the effects of glucagon on the liver?

Answer 28

Glucagon receptor linked to Gs. Glycogen breakdown and gluconeogenesis increase. Presence of G6Pase allows glucose export. Fatty acids used as an energy source and for ketone body production.

Question 29

What are the effects of glucagon on fat and muscle?

Answer 29

At high levels causes: lipolysis in adipocytes, proteolysis (releasing AA for gluconeogenesis) in muscle.

Question 30

What organ clears glucagon?

Answer 30

Liver

Question 31

Aside from the pancreas, from where else is somatostatin released?

Answer 31

D cells of stomach, duodenum and pancreas. Release stimulated by lumenal H+ and inhibited by ACh.

Question 32

What is the function of somatostatin?

Answer 32

Acts on G cells to inhibit the release of gastrin. Also inhibits the release of CCK and secretin (and insulin/glucagon if it can get to the cells).

Question 33

What is the effect of exercise on glucose homeostasis?

Answer 33

Adrenaline signals via cAMP to enhance: 1. Glucose production in the liver (inc. Cori cycle) 2. Glycogen breakdown in muscle and GLUT4 insertion 3. Fatty acid release from adipocytes

Question 34

What is the impact of excess glucagon in the type 1 diabetes?

Answer 34

Leads to lipolysis an proteolysis. Gluconeogenesis and ketogenesis in the liver.

Question 35

What are plasma insulin levels in type 2 diabetes?

Answer 35

Often high