3a. Pancreas (Insulin)

Question 1

Body energy =

Answer 1

energy intake - energy output

Question 2

what do the feeding centres do

Answer 2

promote feelings of hunger and the drive to eat

Question 3

what do the satiety centres do

Answer 3

promote feelings of fullness by suppressing the feeding centres

Question 4

what is the glucostatic theory of energy intake

Answer 4

food intake is determined by blood glucose: as [BG] increases, the drive to eat decreases (- Feeding Centre; + Satiety centre)

Question 5

what is the lipostatic theory of energy intake

Answer 5

food intake is determined by fat stores: as fat stores increase, the drive to eat decreases (- feeding centre; + Satiety Centre).

Question 6

what is Leptin

Answer 6

Leptin is a peptide hormone released by fat stores which depresses feeding activity

Question 7

what are the three categories of energy output

Answer 7

1. cellular work - transporting molecules across membranes, growth/repair, storage of energy, etc
2. mechanical work - movement (either large scale with muscles or intracellularly)
3. heat loss - associated with cellular and mechanical, accounts for half of energy output

Question 8

define metabolism

Answer 8

the integration of all biochemical reactions in the body

Question 9

what are the three elements of metabolism

Answer 9

1. extracting energy from nutrients in food
2. storing that energy
3. utilising that energy for work

Question 10

what are anabolic pathways

Answer 10

build up pathways - net effect is synthesis of large molecules from smaller ones, usually for storage purposes

Question 11

what are catabolic pathways

Answer 11

break down pathways - net effect is degradation of large molecules into smaller ones, usually releasing energy for work

Question 12

what is the absorptive state

Answer 12

the state we enter after eating where ingested nutrients supply the energy needs of the body and excess is stored - ANABOLIC PHASE

Question 13

what is the post-absorptive state (i.e. fasted state)

Answer 13

the state we enter between meals and overnight when the pool of nutrients in the plasma decreases and we rely on body stores to provide energy - CATABOLIC PHASE

Question 14

what chemical dominates the anabolic phase

Answer 14

insulin

Question 15

what chemical dominates the catabolic phase

Answer 15

glucagon

Question 16

what do most cells in the body use for energy

Answer 16

fats, carbohydrates or protein

Question 17

why must we maintain blood glucose concentration

Answer 17

because the brain is an obligatory glucose utiliser i.e. can only use glucose for energy - so even if no new carbohydrate is gained by the body [BG] has to be maintained.

(but brain can later use ketone production in starvation)

Question 18

How is blood glucose concentration maintained (in broad terms)

Answer 18

by synthesising glucose from glycogen (glycogenolysis) or from amino acids (gluconeogenesis)

Question 19

what is the normal range of blood glucose concentration

Answer 19

~5mmoles

4.2-6.3mM) (80-120mg/dl

Question 20

what [BG] constitutes hypoglycaemia

Answer 20

<3mM

Question 21

what percentage of the pancreas has endocrine function

Answer 21

1%

Question 22

where are the pancreases endocrine hormones produced

Answer 22

islets of langerhans - small areas of specialised cells

Question 23

what are the 4 types of islet cells and what do they produce

Answer 23

1. alpha cells - glucagon
2. beta cells - insulin
3. delta cells - somatostatin
4. F cells - pancreatic polypeptide

Question 24

What is the purpose of insulin and how does it do this

Answer 24

decreases blood glucose concentration

• increases glucose oxidation
• increases glycogen synthesis
• increases fat synthesis
• increases protein synthesis

Question 25

briefly describe the synthesis of insulin

Answer 25

synthesised as a large preprohormone (preproinsulin) - converted to proinsulin the the ER - asked as granules into secretory vesicles - within vesicle proinsulin is cleaved to give insulin and C-peptide - insulin stored in this form until the beta cell is activated and secretion occurs

Question 26

what stimulates insulin secretion

Answer 26

MAINLY [BG] - but both blood glucose concentration and amino acid concentration

Question 27

where is excess glucose stored

Answer 27

liver/muscle - as glycogen

Question 28

what are amino acids used to make

Answer 28

new proteins with excess converted to fat

Question 29

where are fatty acids stored

Answer 29

liver/adipose tissue - as triacylglycerols (TAG)

Question 30

what are K ATP channels

Answer 30

specialised K+ ion channels that are sensitive to the [ATP] within the cell - found in beta cells

Question 31

How do K ATP channels work when there are high blood glucose levels

Answer 31

1. High glucose levels in blood 2. glucose enters into cell via transport proteins (GLUT 2) 3. Metabolism increases 4. ATP increases 5. K ATP channels close 6. [K+] rise within cell 7. cell depolarises and opens Ca channels 8. Ca2+ entry acts as an intracellular signal 9. Ca2+ signal triggers exocytosis and insulin is secreted

Question 32

How do K ATP channels work when there are low blood glucose levels

Answer 32

1. When [BG] is low, 2. [ATP] is low 3. K ATP channels open so K+ ions flow out 4. removes +ve charge from the cell and hyperpolarises it 5. voltage-gated Ca2+ channels remain closed 6. insulin is not secreted.

Question 33

what are the only insulin sensitive tissues

Answer 33

muscle and adipose - ie require insulin to take up glucose | all other tissues do not require insulin for glucose uptake

Question 34

What is the primary action of insulin

Answer 34

binds to tyrosine kinase receptors on cell membrane of insulin sensitive tissues - increases glucose uptake by these tissues

Question 35

How does insulin increase glucose uptake by cells

Answer 35

binds to receptor - cause signal transduction cascade - stimulates specific glucose transporter GLUT4 (found in the cytoplasm) - GLUT 4 exocytoses to cell membrane - glucose is transported through membrane here Once stimulation by insulin stops – vesicles endocytose back into cell

Question 36

In non-insulin sensitive tissues how does glucose uptake occur

Answer 36

via insulin-independent GLUT transporters GLUT 1 and 3 - basal glucose uptake in many tissues e.g. brain, kidney, RBC GLUT 2 - beta cells of pancreas and liver

Question 37

How does glucose enter into the liver hepatocytes

Answer 37

GLUT 2 transporters take up glucose which enters down concentration gradient

Question 38

How does insulin enhance glucose movement into hepatocytes despite GLUT 2 being insulin independent

Answer 38

alters concentration gradient: 1. Insulin cases signal cascades 2. cause hexokinase to convert glucose into glucose-6-phosphate 3. this keeps glucose concentration low 4. therefore movement of glucose into the cell is favoured (when low insulin the liver synthesises glucose via glycogenolysis and gluconeogenesis, inc. glucose concentration in the cell, gradient changes to favour glucose movement out of cell)

Question 39

How can insulin cause serious arrhythmias

Answer 39

by promoting K+ ion entry into cells stimulating Na+/K+ ATPase

Question 40

summarise the effects of insulin

Answer 40

1. Glucose entry 2. Glycogen stored in muscle and liver 3. Amino acid uptake 4. Protein synthesis 5. Increased fat synthesis – produce glycerol 6. Inhibits gluconeogenesis 7. Stimulation of K+ uptake by stimulating Na+/K+ ATPase

Question 41

5 stimuli that increase insulin release

Answer 41

1. HIGH [BG] 2. increases plasma [amino acid] 3. glucagon 4. vagal nerve activity 5. other (incretin) hormones controlling GI secretion and motility (e.g. gastrin, secretin, CCK, GLP-1, GIP)

Question 42

4 stimuli that inhibit insulin release

Answer 42

1. LOW [BG] 2. Somatostatin (GHIH from pancreas and hypothalamus) 3. Sympathetic alpha2 effects 4. stress eg hypoxia

Question 43

Why is the insulin response to IV glucose load less than the equivalent oral glucose load

Answer 43

IV glucose = increased insulin by direct effect of increased glucose on beta cells BUT Oral glucose = increased insulin by direct effect on beta cells AND vagal stimulation of beta cells PLUS incretin effects