case 6 - insulin and glucagon

Question 1

where is insulin produced

Answer 1

by the beta cells in the pancreas

Question 2

what is insulin responsible for

Answer 2

for regulating the movement of glucose from the blood into the cells

Question 3

how is it released into the bloodstream

Answer 3

in an endocrine fashion

Question 4

what is the structure of insulin

Answer 4

consists of two polypeptide chains, an A chain and a B chain, covalently linked by two inter-chain disulfide bridges. there is a third, intra-chain disulfide bridge

Question 5

what is the first step in the synthesis of insulin

Answer 5

the insulin mRNA is translated as a single chain precursor called preproinsulin. there is then removal of its signal peptide at the N-terminus during insertion at the endoplasmic reticulum

Question 6

what does this generate

Answer 6

proinsulin

Question 7

what happens in the endoplasmic reticulum

Answer 7

the endopeptidases excise a connecting peptide (C - peptide) between the A and B chains. this breaks the single chain into two strands that are help together by disulfide bridgess.

Question 8

what does this generate

Answer 8

the mature form of insulin

Question 9

what happens to the eqimolar amounts of insulin and free c-peptide

Answer 9

they are packaged in the golgi apparatus into storage vesicles which accumulate in the cytoplasm

Question 10

what is the stimulation for insulin release

Answer 10

a rise in glucose levels in the extra cellular fluid

Question 11

glucose is transported into the beta cells via what channels

Answer 11

by facilitated diffusion through GLUT2 channels

Question 12

what does a rise in glucose concentration in ECF cause

Answer 12

causes a rise in glucose concentration in beta cells.

Question 13

what does this lead to

Answer 13

this leads to membrane depolarisation of ATP sensitive K+ channels, opening Ca2+ channels

Question 14

what does this trigger

Answer 14

an influx of calcium

Question 15

what is the two stage process by which an increase in intracellular Ca2+ triggers insulin release

Answer 15

Margination: the process by which insulin storage vesicles move to the cell surface.

Exocytosis: This is fusion of the vesicle membrane with the plasma membrane, with release of the vesicle’s entire contents

Question 16

what are the 2 phases of insulin secretion

Answer 16

Pulsatile release (rapid onset): Short term blood glucose control: clearing absorbed nutrients from the blood following a meal.

Protracted release (longer): Long term insulin release for glucose uptake e.g. for cell growth, cell division, stimulating protein synthesis and DNA replication.

Question 17

what does insulin bind to

Answer 17

a highly specific insulin receptor on cell surfaces

the receptor is a dimer

Question 18

what 2 subunits is the insulin receptor made up of

Answer 18

one alpha chain - exterior of cell membrane
one beta chain - spans cell membrane in a single segment

Question 19

what are these two chains connected by

Answer 19

a single disulphide bond

Question 20

what happens once insulin is detected

Answer 20

the alpha chains move together and fold around the insulin

Question 21

what does this do

Answer 21

this moves the beta chains together making them an active tyrosine kinase

Question 22

what does the active tyrosine kinase initiate

Answer 22

initiates a phosphorylation cascade which results in an increase of GLUT4 expression - a protein channel to allow glucose uptake. the result is an increase in glucose uptake by cells

Question 23

overall, what can insulin be considered as

Answer 23

the anabolic or building hormone - it assists processes that build compounds for storage and decrease processes that break down those storage reserves

Question 24

what stimulates insulin secretion

Answer 24

GI tract hormones
acetylcholiine

Question 25

what inhibits insulin secretion

Answer 25

adrenaline
noradrenaline

Question 26

what is glucagon

Answer 26

the hormone that opposes insulin, so it acts to raise blood glucose levels

Question 27

what is it produced by and what kind of hormone is it

Answer 27

it is a peptide hormone, produced by the alpha cells of the pancreas

Question 28

what is the structure of glucagon

Answer 28

a single chain polypeptide and has no disulphide bridges, making it incredibly flexible

Question 29

what is the synthesis of glucagon

Answer 29

a precursor molecule, proglucagon, undergoes post-translational processing to become a biologically active glucagon

Question 30

how is glucagon secreted

Answer 30

secreted by alpha cells in the islets of Langerhans in the tail of the pancreas.

Question 31

what is detected by alpha cells and what does this lead to

Answer 31

low glucose levels in the blood are detected by alpha cells, stimulating the release of glucagon.

Like insulin, this undergoes margination and exocytosis to be released.

Question 32

what is the mechanism of action of glucagon

Answer 32

glucagon binds to a specific receptor in the membrane, a G protein coupled receptor

Question 33

what does this activate

Answer 33

this activates adenylate cyclase which increases cAMP intracellularly.

Question 34

what does this increase in cAMP lead to

Answer 34

activates protein kinase A, which phosphorylates and activates a number of important enzymes in target cell

Question 35

what are the overall affects of glucagon

Answer 35

Increased glycogenolysis
Decreased glycogenesis
Increased gluconeogenesis
Increased ketogenesis
It also increases lipolysis in adipose tissue.

Question 36

what stimulates glucagon secretion

Answer 36

adrenaline
noradrenaline

Question 37

what inhibits glucagon secretion

Answer 37

GI tract hormones
acetylcholine