L15

Question 1

what is glucose stored as

Answer 1

glycogen

Question 2

what is the normal concentration of glucose in the blood

Answer 2

5mM

Question 3

Insulin and Glucagon are released by the pancreas, in the Islets of Langerhans

Answer 3

True

Question 4

what are the cell types in the pancreas

Answer 4

α cells (15 – 20%) – produce glucagon

β cells (65 – 80%) – produce insulin and amylin

γ cells (3 – 10%) – produce somatostatin

Question 5

how many amino acids does insulin have when first secreted

Answer 5

84

Question 6

where is pro insulin produced from

Answer 6

Golgi

Question 7

pro insulin is biologically active

Answer 7

no

Question 8

how is pro insulin activated

Answer 8

by prohormone convertase 1 and 2 remove 33 amino acids (C chain)

Question 9

what are the chains in the final insulin

Answer 9

A Chain – 21 amino acids
B Chain – 30 amino acids

Question 10

where is insulin stored

Answer 10

Stored within secretory granules of the
β cells

Question 11

what else is stored with insulin

Answer 11

some pro-insulin and the C peptide

Question 12

C peptide is inactive

Answer 12

false

Question 13

how does Glucose induce insulin secretion

Answer 13

Infusion of glucose to maintain elevated glucose immediately promotes insulin
secretion from β cells

First phase – release of insulin stored within secretory granules

Second phase – synthesis / secretion of new insulin

Very little binding of insulin to plasma proteins – circulates in free form

Insulin degraded by insulinase (mainly liver but also muscle / kidneys)

Plasma half life ~6 min so effects on tissues
rapidly reversible

C chain is more stable – assayed in order to provide an indicator of insulin secretion

Question 14

when is insulin at maximum concentration

Answer 14

when glucose is at ~9mM

Question 15

how does glucose level in the blood cause insulin secretion

Answer 15

β cells express a type 2 glucose transport system (GLUT2)

This system is hormone-insensitive and
therefore always active

In the β cells Glucose is phosphorylated to glucose 6-P by glucokinase and metabolised by glycolysis and mitochondrial oxidation to generate ATP / ADP

β cells express a ATP-sensitive K+ channels
These channels are open at normal levels of ATP

High levels of ATP close channel

Since these channels set the membrane potential (Vm) – channel closure causes depolarization

when Vm goes up to -25mV from -65 mV, voltage-gated Ca2+ channels open

Ca 2+ influx leads to insulin secretion

Question 16

where is pancreatic blood drained into

Answer 16

hepatic portal vein

Liver therefore first organ to be exposed to insulin

Portal circulation transports glucose from gut to liver

Question 17

what are the features of insulin receptors

Answer 17

Dimeric receptor

Each receptor consists of 2 subunits α and β

Insulin binding promotes receptor
dimerization and activation (see previous lecture)

Once the receptors dimerise, then the 2 subunits phosphorylate each other at multiple tyrosine residues

Question 18

what happens after insulin binds the receptor

Answer 18

active receptors phosphorylate IRS-1

IRS-1 activates PI3K resulting to cellular response to insulin

IRS-1 also activates MAPK cascade, resulting in stimulating cell growth and survival

Question 19

how does insulin promote glucose uptake by the liver

Answer 19

through glucose transport system (GLUT4)

In unstimulated cells GLUT4 is mainly found in intracellular membrane vesicles and not in plasma membrane

Plasma membrane therefore has low glucose permeability

Insulin activates PI3K…

…which then activates protein kinase B (PKB)

Which evokes the translocation of
GLUT4 by phosphorylation to the plasma membrane….

…and thus allows glucose uptake into the hepatocyte

Question 20

what does glycogen synthesis look like normally

Answer 20

active (dephosphorylated) GSK-3 phosphorylates (inactivates) glycogen synthase

no glycogen synthesis

Question 21

how does insulin promote glycogen synthesis

Answer 21

PKB activated by insulin phosphorylates (inactivates) GSK

leads to dephosphorylation of glycogen synthase

active glycogen synthase promotes glycogen synthesis