Endocrine pancreas 1 + 2

Question 1

Define the term obligatory glucose utiliser and give an example of this

Answer 1

= can only meet its energy demands from glucose and no alternative source, i.e. BRAIN

Question 2

State the range of plasma glucose that may be expected in normal resting subjects who have fasted overnight

Answer 2

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

average 5mM

Question 3

Describe the process by which insulin is released

Answer 3

Released when there’s high BG (main stimulus), although amino acids in blood can also stimulate its release

Beta cells have a specific type of K+ ion channel that is sensitive to the [ATP] within the cell = KATP channel

When glucose is abundant, it enters cells through glucose transport proteins (GLUT) and metabolism increases –> this increases [ATP] within the cell causing the KATP channel to close. Intracellular [K+ ] rises, depolarising the cell –> triggers voltage-dependent Ca2+ channels to open and subsequently insulin vesicle exocytosis into the circulation

Question 4

Energy (food) intake is determined by the balance of activity in what 2 hypothalamic centres

Answer 4

Feeding centre - promotes feelings of hunger

Satiety centre - promotes feelings of fullness

Question 5

Describe the glucostatic theory

Answer 5

as [BG] increases, the drive to eat decreases

Question 6

Describe the lipostatic theory + what hormone suppress feeding

Answer 6

as fat stores increase, the drive to eat decreases

Leptin, a peptide hormone released by fat stores, depresses feeding activity

Question 7

What are anabolic pathways

Answer 7

Build Up. Net effect is synthesis of large molecules from smaller ones, usually for storage purposes

Question 8

What are catabolic pathways

Answer 8

Break Down. Net effect is degradation of large molecules into smaller ones, releasing energy for work

Question 9

After eating we enter an Absorptive State where ingested nutrients supply the energy needs of the body and excess is stored

Is this a catabolic or anabolic phase

Answer 9

anabolic

Question 10

Between meals and overnight, the pool of nutrients in the plasma decreases and we enter a post-absorptive State (aka fasted state) where we rely on body stores to provide energy

Is this a catabolic or anabolic phase

Answer 10

catabolic

Question 11

Most cells can use fats, carbohydrates or protein for energy but the brain can only use … except when…

Answer 11

glucose

except in extreme starvation – use ketones

Question 12

When no new carbohydrate is gained by the body we MUST still maintain blood glucose concentration [BG] sufficient to meet the brain’s requirements

2 ways this can be done:

Answer 12

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

Question 13

Hypoglycaemia when [BG] is

Answer 13

3mM or less

Question 14

Lipogenesis (converting glucose to fat) and glycogenesis (converting glucose to glycogen) are stimulated by what hormone + why

Answer 14

Insulin

they are processes that uptake glucose

Question 15

Glycogenolysis + gluconeogenesis are stimulated by what hormone + why

Answer 15

Glucagon

They are processes that produce glucose which is what glucagon wants (to raise BG)

Question 16

What percentage of the pancreas has an endocrine function

Answer 16

1%

Question 17

4 types of islet cells (making up islets of langerhans)

Answer 17

alpha
beta
delta
F

Question 18

What do the following islet cells produce

• alpha
• beta
• delta
• F

Answer 18

glucagon

insulin

somatostatin (GHIH)

pancreatic polypeptide

Question 19

Excess glucose is stored as what 2 things (2)

Answer 19

glycogen in liver and muscle

triacylglycerols (TAG) in liver and adipose tissue

Question 20

What is the only hormone that lowers [BG]

Answer 20

Insulin

Question 21

How are fatty acids stored

Answer 21

as triglycerides in adipose tissue and liver

Question 22

How is insulin synthesised (4)

Answer 22

Synthesized as a large preprohormone (preproinsulin) which is then converted to proinsulin in the ER

Proinsulin is then packaged as granules in secretory vesicles with proteolytic enzymes

Within the granules the proinsulin is cleaved again to give insulin and C-peptide

Insulin is stored in this form until the beta cell is activated and secretion occurs

Question 23

Sites of action of insulin (2)

Answer 23

Muscle
+
Adipose
tissue

Question 24

Mechanism of action of insulin on BG levels (2)

• what receptors does it bind to
• what is mobilised to cell membrane

Answer 24

Binds to tyrosine kinase receptors on the cell membrane of insulin-sensitive tissues (muscle and adipose tissue)

Stimulates GLUT-4 transporters which reside in the cytoplasm to migrate to the membrane in order to let glucose into the cell and so decrease BG

Question 25

Some cells are insulin sensitive but not insulin dependent, what tissues are insulin dependent (2)

Answer 25

Skeletal muscle + adipose tissue

Question 26

Is the liver insulin sensitive

Answer 26

No

Question 27

How does the liver uptake glucose | -what transporters are involved

Answer 27

by GLUT 2 transporters, which are insulin independent. Glucose enters down concentration gradient

Question 28

Although the liver is not insulin sensitive (i.e. insulin has no direct effect on liver), glucose transport in and out hepatocytes is still INDIRECTLY affected by insulin status in order to maintain BG Describe this indirect effect of insulin status on glucose transport in/out of hepatocytes when - plasma insulin is high - plasma insulin is low

Answer 28

When BG is high so HIGH insulin, insulin activates hexokinase which lowers [glucose] intracellularly, creating a gradient favouring glucose movement into the cells When BG is low so LOW insulin, liver synthesises glucose via glycogenolysis and gluconeogenesis, increasing [glucose] intracellularly creating a gradient favouring glucose movement out of the cells

Question 29

As well as insulin decreasing [BG], what additional actions does it have (6)

Answer 29

Increases glycogen synthesis in muscle and liver by stimulating glycogen synthase and inhibits glycogen phosphorylase Increases amino acid uptake into muscle, promoting protein synthesis. Increases protein synthesis and inhibits proteolysis Increases triacylglycerol synthesis in adipocytes and liver i.e. stimulates lipogenesis Inhibits gluconeogenesis in the liver (to stop more glucose production) Promotes K+ ion entry into cells by stimulating Na+/K+ ATPase

Question 30

Insulin half life

Answer 30

around 5 mins -short like all peptide hormones

Question 31

Stimuli which promote insulin release (5)

Answer 31

Increased [BG] Increased [amino acids] in plasma Glucagon (indirectly; as glucagon stimulates gluconeogenesis which creates glucose so then insulin would be needed to take up the glucose produced) Other hormones controlling GI secretion/motility, e.g. gastrin, secretin Vagus nerve activity

Question 32

Stimuli which inhibit insulin release (4)

Answer 32

Low [BG] Somatostatin (GHIH) Sympathetic a2 receptor effects - lower BP Stress, e.g. hypoxia

Question 33

Is the insulin response to an IV glucose load the same as that to an oral loading of the same amount of glucose

Answer 33

No because oral glucose also stimulates the vagus nerve which stimulates B cells to release insulin as well as release of GI hormones that trigger digestive processes so oral glucose stimulates B cells twice (by direct effect of increased glucose on B cells and vagal stimulation of B cells) whereas IV glucose just stimulates insulin release due to the effect of increased glucose on B cells

Question 34

Primary function of glucagon + what organ does it mainly act on

Answer 34

Raise [BG] liver

Question 35

What are the counter regulatory hormones of glucose (i.e. the 4 [BG] raising hormones) (4)

Answer 35

glucagon, adrenaline/epinephrine, cortisol, GH

Question 36

Glucagon is most active in the absorptive or post-absorptive state

Answer 36

post-absorptive | -as glucose has been absorbed so now need more glucose back in blood

Question 37

Mechanism of action of glucagon on raising BG levels - what receptor does it bind to + where is this receptor - once its receptor is activated, what 3 processes are stimulated to raise to produce glucose and raised BG

Answer 37

Glucagon binds to its G-protein coupled receptors (on liver) linked to the adenylate cyclase/cAMP system which when activated, phosphorylate specific liver enzymes, resulting in: 1. increased glycogenolysis (to put glucose in blood) 2. increased gluconeogenesis (to put glucose in blood) 3. formation of ketones from fatty acids (for brain and peripheral tissues)

Question 38

When glucose drops below what level does glucagon release increase dramatically

Answer 38

Glucagon release is relatively constant although secretion increases dramatically when [BG] < 5.6mM

Question 39

What stimuli is common between insulin and glucagon release (i.e. stimulates them both to be released) + why is it important for both to be released in response to this stimuli

Answer 39

Amino acids in plasma - esp important for both to be released after a HIGH PROTEIN, LOW CARB MEAL - as amino acids are a stimuli of insulin, after a protein rich meal, insulin would cause glucose uptake leading to a lowered BG - however if it weren't for the effect of amino acids on glucagon as well then the insulin stimulating effects of amino acids would result in a very low BG in the case of a HIGH PROTEIN, LOW CARB MEAL as that wouldn't provide much glucose in the first place

Question 40

Stimuli that promote glucagon release (5)

Answer 40

Low BG High plasma amino acid conc. (also a stimuli of insulin release) Sympathetic innervation & epinephrine, b2 effects Cortisol Stress, e.g. exercise, infection

Question 41

Stimuli that inhibit glucagon release (4)

Answer 41

High BG Free fatty acids & ketones Insulin Somatostatin (GHIH)

Question 42

How does autonomic (sympathetic/parasympathetic) activity influence release of insulin/glucagon - sympathetic - parasympathetic

Answer 42

Increased sympathetic activation promotes glucose mobilization --> increased glucagon, increased epinephrine and inhibition of insulin, all appropriate for fight or flight response Increased parasympathetic activity (vagus) --> increased insulin and to a lesser extent increased glucagon, in association with the anticipatory phase of digestion

Question 43

Somatostatin is a peptide hormone secreted by what 2 things

Answer 43

Delta cells of the pancreas | Hypothalamus

Question 44

Main pancreatic function of somatostatin (GHIH) | + other functions (2)

Answer 44

Inhibit GI tract activity -to slow down nutrient absorption Suppresses the release of insulin and glucagon in a paracrine fashion, but isn't a counter-regulatory hormone in the control of BG Inhibits secretion of GH from AP

Question 45

Describe how glucose metabolism can change in times of stress (exercise, starvation, diabetes) - talk about exercise specifically

Answer 45

Exercise increases insulin sensitivity of muscle and causes an insulin INDEPENDENT increase in GLUT4 transporters recruited to the membrane (i.e. transporters are recruited even if insulin is absent so exercise causes glucose uptake independent of insulin) This effect persists for hours after exercise and regular exercise can produce prolonged increases in insulin sensitivity

Question 46

Describe how glucose metabolism can change in times of stress (exercise, starvation, diabetes) - talk about starvation specifically

Answer 46

When nutrients are scarce, body relies on stores for energy, i.e. adipose tissue is broken down, fatty acids + glycerol are released Free fatty acids readily used by most tissues as energy and liver will convert excess fatty acids to ketone bodies to provide additional energy for muscle & brain Brain adapts to use ketones after a while of starvation which allows protein to be SPARED instead of being broken down into gluconeogenic substrates (don't want this because loss of protein weakens body and makes it vulnerable to infection)

Question 47

How can type 1 DM lead to ketoacidosis

Answer 47

Arises due to lack of insulin As there's no insulin to uptake glucose, body finds other forms of energy to use (breaking down adipose tissue to fatty acids); free fatty acids are readily used by most tissues and liver converts excess fatty acids to ketone bodies However, if not managed with insulin injection then consistent hyperglycaemia and no insulin --> excessive ketone body production --> blood becomes too toxically acidic --> death if untreated

Question 48

How can ketones be detected clinically (2)

Answer 48

In urine and breath

Question 49

Describe how the glucose tolerance test is used to detect hyperglycaemia

Answer 49

Hyperglycaemia Glucose tolerance test - fasting [BG] measured then a glucose load ingested - [BG] should normally return to fasting level within an hour - elevation of [BG] after 2 hours indicated diabetes HOWEVER THIS TEST DOES NOT DISTINGUISH BETWEEN TYPE 1 AND 2

Question 50

How to convert plasma glucose measurement from mg/dl (US) to mM (UK) What is 90mg/dl (=900mg/L) plasma glucose in mM/L

Answer 50

Divide the measurement in mg/dl by the molecular weight of glucose which is 180g (900mg/L) / 180= 5mM/L

Question 51

Complications of hyperglycaemia in DM

Answer 51

Retinopathy Neuropathy Nephropathy Cardiovascular Disease