Trigger 1: Insulin secretion

Question 1

Normal blood glucose

Answer 1

4-7mmol/l

Question 2

When is blood glucose highest

Answer 2

after food

Question 3

factors that affect BG

Answer 3

-exercise -food -illness -stress

Question 4

Insulin

Answer 4

• released from the B-cells in the islets of langerhans - increases uptake of glucose lowering blood sugar - stimulate glycogensis - inhibits glycolysis (Glycogen synthesis in skeletal muscle and liver and Increased lipogenesis and inhibition of gluconeogenesis in liver)

Question 5

Glucagon

Answer 5

-released from alpha cells - increases blood glucose - inhibition of glycolysis and glycogenesis (i.e. decreases glycogen production) -stimulates glucoseneogenesis and glycogenolysis

Question 6

receptor for glucagon is a

Answer 6

GPCR found on liver, increases cAMP and PKA

Question 7

Beta cells

Answer 7

Insulin- decrease BG

Question 8

Alpha cells

Answer 8

Glucagon- increase BG

Question 9

When BG is high

Answer 9

1) beta cells stimulated to release insulin into blood 2) body cells and liver take up more glucose- stored as glycogen in liver 3) BG declines to a set point. Stimulus for insulin release diminished

Question 10

When BG is low

Answer 10

1) Alpha cells stimulated to release glucagon 2) glucagon causes liver to break glycogen down and releases glucose into the blood 3) glucose level rises

Question 11

How many GLUT transporters

Answer 11

14 main

Question 12

GLUT 1

Answer 12

o Found in most cells. o Does not require insulin stimulation. o Facilitated diffusion of glucose o Works with GLUT3 to allow glucose across BBB

Question 13

GLUT 2

Answer 13

o Transports glucose when BGL is high o Metabolic trigger to coordinate insulin secretion o LIVER and B cells

Question 14

GLUT 3

Answer 14

o Brain o Higher affinity for glucose than other GLUTs

Question 15

GLUT 4

Answer 15

o Liver, muscle and adipose tissues o Activated by Insulin signalling pathway o GLUT4 vesicles fuse with the plasma membrane and allows glucose to enter the cell

Question 16

GLUT 5

Answer 16

o Intestinal tissue, kidney and spermatozoa o Fructose transporter

Question 17

Which GLUT is activated during the insulin signalling pathway

Answer 17

GLUT 4

Question 18

which GLUT signals for B cells to release insulin

Answer 18

GLUT2

Question 19

action of glucagon

Answer 19

Increase BG - causes glycogen to break down in liver via glucagon receptors to increase cAMP and PKA - inhibits glycolyis and glycogenesis -stimulates glucoseneogenesis - prevent glycolysis

Question 20

insulin acts on

Answer 20

muscle, adipose and liver

Question 21

response to insulin has how many phases

Answer 21

2

Question 22

phase 1 of insulin release

Answer 22

initially rapid but transient bursts of insulin secretion. Probably due to the release of insulin from granules that directly adjacent to CM

Question 23

phase 2 of insulin release

Answer 23

If BGL remains high, then rise in insulin secretion is sustained due to the release of both stored and newly synthesises insulin

Question 24

Outline the molecular signalling cascade by which insulin promotes glucose uptake in adipose tissue

Answer 24

1) Insulin binds to receptor and causes dimerization and auto phosphorylation of tyrosine residues 2) Binding and phosphorylation of adaptor protein e.g. IRS 3) Activation of P13K, which phosphorylates PIP2 to PIPs 4) Phosphorylation of AKt 5) Causes GLUT4 vesicle to translocate to the cell membrane 6) Allows uptake of glucose from the blood stream by facilitated diffusion

Question 25

Activates PKb/AKT (insulin signalling pathway) causes

Answer 25

• GLUT4 translocation to the plasma membrane/glucose uptake in adipocytes and skeletal muscle • Glycogen synthesis in skeletal muscle and liver • Increased lipogenesis and inhibition of gluconeogenesis in liver

Question 26

2 types of stimulated insulin release

Answer 26

(1) Nutrient stimulated release (e.g. amino acids and fatty acids) (2) Neuronal stimulation of insulin secretion

Question 27

Nutrient stimulated release (e.g. amino acids and fatty acids)

Answer 27

• GLUT2 has a lower affinity for glucose than GLUT4 1. ATP ( produced due to detection of insulin/ amino acids) causes B cell K+ channels to close 2. Leading to membrane depolarisation (becomes more negative) 3. Causing Ca2+ gates to open 4. Ca2+ influx 5. Release of insulin granules

Question 28

(2) Neuronal stimulation of insulin secretion

Answer 28

• Sympathetic- Prevents insulin secretion: o Inhibits cAMP, so PKA not activated • Parasympathetic- stimulates insulin secretion by stimulating Ach

Question 29

Sympathetic

Answer 29

Prevents insulin secretion: o Inhibits cAMP, so PKA not activated

Question 30

Parasympathetic

Answer 30

stimulates insulin secretion by stimulating Ach

Question 31

How are B cell specialised for insulin secretion? (5)

Answer 31

1) GLUCOKINASE 2) GLUT2 has a low affinity for glucose 3) Islets are highly vascularised to release insulin into the bloodstream 4) Number of B cells are tightly regulated 6) Highly differentiated- many unique TFs

Question 32

Glucokinase

Answer 32

is also known as hexokinase IV and catalyses the conversion of glucose to glucose 6 phosphate

Question 33

glucokinase is a key componenet of

Answer 33

glucose sensing machinery- - Sets the threshold for glucose stimulated insulin secretion

Question 34

characteristics of glucokinase

Answer 34

(1) Low affinity for glucose (S0.5 8-10mM) (2) Lack of inhibition by substrate

Question 35

signalling pathway within Bcells

Answer 35

Glut2 senses high conc of glucose 1) Glucose is converted to glucose-6-p by glucokinase 2) G-6-P is converted to F-6-P 3) to pyruvate 4) to acetyl-CoA 5) to cholesterol, fatty acids etc

Question 36

processing of insulin within beta cells

Answer 36

insulin is synthesises as a preproinsulin in the ribosome of the RER. Preproinsulin is then cleaved to proinsulin, which is transported to the Golgi apparatus where is it packaged into secretory granules located close to the cell membrane

Question 37

proinsulin is cleaved into

Answer 37

proinsulin is cleaved into equimolar amount son insulin and C peptide in the secure granules

Question 38

what is insulin packaged into

Answer 38

secretory granules

Question 39

where are secretory granules located

Answer 39

close to the membrane to allow rapid release

Question 40

processing of insulin within beta cells (easy)

Answer 40

1) preproinsuline is cleaved to proinsulin 2) proinsulin is cleaved to insulin and c-peptide in equal amounts this is why C-peptide is a marker of insulin

Question 41

Insulin secretion from B cells

Answer 41

1) unactivated b cell will have open K+ channels 2) when GLUT2 senses a high enough BP, it opens and allows the influx of glucose 3) glucose is converetd to glucose 6 phosphate by glucokinase 4) glucokinase is further metabolised to produce ATP 5) ATP causes K+ channels to close 6) this depolarises the membrane (becomes more negative) 7) stimulates the influx of calcium 8) calcium causes insuli secretry granules to fuse withteh cell membrane