10. Pancreas, insulin and glucagon

Question 1

what are 2 main functions of pancreas

Answer 1

1- exocrine production/secretion of alkaline digestive enzymes directly into duodenum via pancreatic duct - 99% of gland

2. endocrine hormone production in Islets of Langerhans - 1% of gland

Question 2

name 2 pancreatic endocrine cell types and the hormones they produce

Answer 2

alpha cells: glucagon

beta cells: insulin

Question 3

what is the normal glucose conc. in blood

Answer 3

3.3-6 mmol/L

Question 4

what is the renal threshold and when might this change physiologically

Answer 4

limit of glucose kidney can reabsorb - 10 mmol/L

increased in elderly, decreased in pregnancy

Question 5

what happens when renal threshold is exceeded

Answer 5

glucosuria (glucose in urine)

Question 6

what are the main controllers of plasma glucose

Answer 6

insulin (released when high glucose to decrease conc.)

glucagon (released when low glucose to increase conc.)

Question 7

what is the function/location of GLUT1

Answer 7

located in RBC and blood/brain barrier endothelial cell membranes

allow basal low level glucose uptake required to sustain respiration

Question 8

what is the function/location of GLUT2

Answer 8

pancreatic beta cells: allows glucose entry… increased ATP… insulin release

hepatocytes: bidirectional transporter allowing glucose entry for glycogenesis and glucose exit after gluconeogenesis

Question 9

what is the function/location of GLUT3

Answer 9

main glucose transporter in brain: high glucose affinity isoform allowing glucose entry even when low plasma glucose

Question 10

what is the function/location of GLUT4

Answer 10

skeletal muscle and adipose tissue: allows insulin-regulated glucose uptake

Question 11

describe the structure of insulin

Answer 11

2 polypeptide chains (A and B chains) covalently linked by 2 disulphide bonds

3rd intra-chain disulphide bond within A chains

Question 12

describe the synthesis of insulin

Answer 12

i) synthesised as preproinsulin (single polypeptide chain) on rER ribosome
ii) enters rER lumen - signal peptide is cleaved to produce proinsulin
iii) proinsulin folds to ensure correct alignment of cysteine residues, disulphide bond formation
iv) proinsulin transported to Golgi and stored in secretory granule
v) proteolysis of polypeptide in vesicle to form insulin + C-peptide

Question 13

how is inuslin transported in blood and what is consequence of this

Answer 13

water soluble so no transporter protein

so has short 1/2 life (5min) - allows it to respond very quickly to glucose conc. on min to min basis

Question 14

what type of R is the insulin R

Answer 14

tyrosine kinase R on target cell membrane (dimer of 2 subunits composed of alpha and beta chains linked by 1 disulphide bond)

Question 15

how does insulin decrease blood glucose

Answer 15

1- increases glucose uptake into skeletal muscle and adipose - GLUT4 translocation to membrane
2- increases glycogenesis in liver
3- decreases glycogenolysis in liver and muscle
4- decreases gluconeogenesis in liver

Question 16

how does insulin decrease blood lipids

Answer 16

1- decreases lipolysis in adipose
2- increases lipogenesis and fatty acid esterification in adipose and liver
3- increases lipoprotein lipase in capillary beds

Question 17

how does insulin decrease blood amino acids

Answer 17

1- increases amino acid uptake in liver, muscle and adipose
2- increases protein synthesis in liver, muscle and adioise
3- decreases proteolysis in liver, skeletal and cardiac muscle

Question 18

describe mechanism of insulin release

Answer 18

i) glucose entry into pancreatic beta cell… glucose metabolism… ATP production
ii) high ATP inhibits ATP-sensitive K+ channels… decreased K+ efflux… membrane depolarisation
iii) activates voltage-gated Ca2+ channels… calcium influx
iv) insulin vesicle margination and insulin exocytosis

Question 19

which factors stimulate or inhibit insulin release

Answer 19

stimulated by: metabolic signals (high glucose, fatty acids and amino acids), GI tract hormones (cholecystokinin, secretin and gastrin) and acetylcholine

inhibited by: adrenaline and NA

Question 20

describe the structure of glucagon

Answer 20

single polypeptide chain with no disulphide bonds - flexible structure that takes active conformation on receptor binding

Question 21

describe the synthesis of glucagon

Answer 21

synthesised on rER ribosome in pancreatic alpha cells as preproglucagon and post-translationally processed in similar but simpler way to insulin

Question 22

which factors stimulate or inhibit glucagon release

Answer 22

stimulated by: low blood glucose (and high amino acids), adrenaline and NA release

inhibited by: high blood glucose and insulin

Question 23

how is glucagon transported in blood and what is consequence of this

Answer 23

water soluble so no transporter protein

so has short 1/2 life (5min) - allows it to respond very quickly to glucose conc. on min to min basis

Question 24

what type of R is the glucagon R

Answer 24

GPCR

Question 25

how does glucagon increase blood glucose

Answer 25

1- increases gluconeogenesis in liver

2- decreases glycogenesis and increases glycogenolysis in liver

Question 26

what is the effect of glucagon in starvation

Answer 26

increases ketone body production in liver

Question 27

how does glucagon increase blood fatty acids

Answer 27

increases lipolysis in adipose