lecture 23 - blood glucose homeostasis and insulin action

Question 1

insulin is secreted in conditions of

Answer 1

high blood glucose

Question 2

insulin lowers

Answer 2

blood glucose

Question 3

glucagon in secreted in conditions of

Answer 3

low blood glucose

Question 4

glucagon increases

Answer 4

blood glucose

Question 5

pancreatic islets (islets of langerhans) are in the pancreas, contain

Answer 5

alpha, beta and delta cells that secrete hormones

Question 6

the cells have a dense capillary network so they can

Answer 6

detect the blood glucose levels and can release the hormones very quickly

Question 7

regulators of insulin release

Answer 7

glucose +
amino acids +
neural input (cholinergic) +
gut hormones (GLP1, GIP) +
adrenaline -
somatostatin -

Question 8

regulators of glucagon release

Answer 8

glucose -
insulin -
amino acids +
neural output (stress) +
gut hormones -
cortisol +

Question 9

insulin production

Answer 9

transcriptions
translation
pre-proinsulin
cleavage to proinsulin (in RER)
cleavage to insulin and C-peptide (in golgi)
insulin accumulates in secretary granules
secretion - exocytosis

Question 10

after formation of disulphide bonds residues 31 to 65 are cleaved forming

Answer 10

c-peptide
insulin (52 aa in two chains)

Question 11

insulin is stored in a

Answer 11

hexatrimeric form (3 dimers sit together) with zinc in the middle until they are released by beta cells

Question 12

insulin composed of an

Answer 12

A and B chain
the chains are connected by disulphie bridges

Question 13

half life of insulin of

Answer 13

is short

Question 14

C- peptide is not degraded so you can use it to test the concentration and for diagnosis

Answer 14

eq for type 1 diabetes levels of c peptide would be low

Question 15

stimulation of insulin secretion by glucose (basal glucose)

Answer 15

beta cells have a glucose transporter
glucose inside the cell is converted to glucose6-P by glucokinase (this is the rate limiting step, glucokinase has a low affinity to glucose)
glycolysis causes glucose 6-P to turn to pyruvate
pyruvate enters the mitochondria, undergoes krebs cycle and ETC, and ATP is released
when theres low glucose levels not much ATP is released causing the K-ATP channels stay open so potassium ions move out the cell, and membrane potential remains at -60 mV
the voltage gates calcium channels also stay shut, so theres no calcium entering the cell and no insulin is released

Question 16

when blood glucose levels rise

Answer 16

glucokinase is more active
more ATP is released into the cell
potassium ATP senses this change and causes the channel to close, meaning the membrane potential starts to depolarise
depolarisation to -40 mV causes the voltage gates calcium channels to open
high cytoplasmic calcium
high insulin secretion

Question 17

function of insulin (tells tissues what to do with the glucose)

Answer 17

1.muscle
takes up glucose in the absorptive state in response to insulin and converts it to glycogen or oxidises it as a source of energy
2. adipose
takes up glucose in response to insulin and converts it to fat.
3. liver
extracts about 1/3rd of glucose and converts in to glycogen
surplus glucose and amino acids are converted to lipids that can be taken up by the adipose cells

Question 18

liver glycogen is the first line of defence against

Answer 18

declining blood glucose concentration

Question 19

glycogen

Answer 19

branched polymer of glucose molcules

Question 20

glucose can bind to each other between

Answer 20

1-4 and 1-6

Question 21

branching allows

Answer 21

more points to breakdown

Question 22

what happens to dietary glucose when the liver stores are full

Answer 22

its converted to fat:
glucose undergoes glycolysis into pyruvate
pyruvate enters the mitochondria
Krebs cycle only gets as far as citrate and the citrate comes out the mitochondria
citrate to acetyl CoA to malonyl CoA
then converted into fatty acids (palmitate, common FA)
conjoined with glycerol 3-P to make triglycerides
then turned into VLDL and secreted into the blood

Question 23

fasting state response

Answer 23

muscles:
protein to amino acids
release amino acids into the bloodstream
adipose:
triglycerides to fatty acids and glycerol and release FA to blood stream which muscles can use
liver:
glucagon signals to liver to convert glycogen back to glucose and release into blood stream
glucagon also tells liver to convert aa released by muscle to convert them back to glucose (gluconeogenesis - uses other substrates to glucose)
liver can take up FA and convert to energy for itself
liver can also convert FA to ketone bodies, which can fuel the brain (cant use fatty acids as they cant cross BBB)

Question 24

during fasting glucose is produced by

Answer 24

glycogenolysis and gluconeogenesis

Question 25

insulin action on liver

Answer 25

+ glycogen synthesis
+ fatty acid/ TG synthesis
+ protein synthesis
- glycogen degradation
- gluconeogenesis

Question 26

insulin action on muscle

Answer 26

+ glucose transport (uptake, use and storage)
+ glucose synthesis
+ glucose oxidation
+ protein synthesis

Question 27

insulin action of adipose tissue

Answer 27

+ glucose transport
+ triglyceride synthesis
- triglyceride breakdown, release of FA

Question 28

insulin action in muscle

Answer 28

in absence of insulin the muscle cant uptake glucose because glucose transporter (GLUT4) is in vesicles and not in the plasma membrane
when insulin binds to membrane it causes translocation of GLUT4 to go to membrane and once its there in brings to glucose in
insulin also tells the muscle to increase the formation of glycogen by activating glycogen synthase
also tells cell to metabolise more glucose by increasing activity of pyruvate dehydrogenase (convertion of pyruvate to Acetyl CoA)

Question 29

insulin action in adipose tissue

Answer 29

same transporter (GLUT4)
translocation of GLUT4
insulin increase fatty acid synthesis
and increases transcription of key enzymes (fatty acid synthase and acetyl-CoA carboxylase)
insulin switches off enzyme that switches triglycerides back to fatty acids (hormone sensitive lipase)
increases amount of fat that the adipose cell can take up, insulin causes lipoprotein lipase to convert triglycerides into FA + monoglycerides so they can be taken up into the adipose cell and converted back to triglycerides

Question 30

insulin action in the liver

Answer 30

liver expresses GLUT2
insulin increases the transcription of glucokinase
also stimulates conversion to glycogen by activating glycogen synthase
inhibits activity of glycogen phosphorylase
insulin increases transcription of FA synthase and acetyl-CoA carboxylase (production of triglycerides)
switches off PEPCK and glucose 6-phosphatase (these are used in conversion back to glucose - gluconeogenic enzymes)

Question 31

glycogen synthase

Answer 31

when glycogen synthase is phosphorylated its inactive
when its dephosphorylated its active
insulin (in liver and muscle) activates protein phosphatase 1 which removes phosphate groups and activates glycogen synthase
G6P and glucose can also stimulate this enzyme

Question 32

glycogen phosphorylase

Answer 32

switching off glycogen breakdown, glycogen phosphorylase takes glycogen to G1P then back to glucose
when glycogen phosphorylase is phosphorylated its active
insulin causes dephosphorylation of glycogen phosphorylase which makes it inactive
glucagon can increase the activity of an enzyme that phosphorylates glycogen phosphorylase