Endocrine pancreas 1+2

Question 1

The balance of activity in which 2 hypothalamic centres determines energy (food) intake? and how is it controlled?

Answer 1

Feeding centre - promotes feelings of hunger and drive to eat

Satiety centre - promotes feelings of fullness by suppressing the Feeding centre

In both - activity is controlled by a complex balance of neural and chemical signals as well as the presence of nutrients in plasma

Question 2

What is the glucostatic theory

Answer 2

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

Question 3

What is the lipostatic theory?

Answer 3

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

Question 4

What is leptin?

Answer 4

A peptide hormone released by fat stores which depresses feeding activity

Question 5

How does obesity result?

Answer 5

imbalance in energy balance - too much input not enough output

rare for it to come about due to metabolic problem

Question 6

What are the 3 categories of energy output?

Answer 6

Cellular work - transporting molecules across membranes; growth and repair; storage of energy (eg. fat, glycogen, ATP synthesis)

Mechanical work - movement, either on large scale using muscle or intracellularly (voluntary – posture etc and involuntary – cellular level etc)

Heat loss - associated with cellular and mechanical work accounts for half our energy output

Question 7

What is the only part of energy output that can be regulated?

Answer 7

The mechanical work doen by skeletal muscle

Question 8

What are the 3 elements of metabolism

Answer 8

Extracting energy from nutrients in food

Storing that energy

Utilising that energy for work

Question 9

Why is it important to maintain blood glucose concentration?

Answer 9

We need sufficient levels of glucose in the blood to meet the brain’s requirements

The brain gets first dibs on any glucose in the blood (it will take it to the detriment of any other tissues in the body) – needs it to function properly

hypoglycaemia can lead to coma and death

Question 10

What is glycogenolysis?

Answer 10

synthesising glucose from glycogen (stored in muscle)

Question 11

What is gluconeogenesis?

Answer 11

Synthesising glucose from amino acids

Question 12

Normal blood glucose range

Answer 12

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

remember 5 mmoles as this is pretty much normal

Question 13

What normally happens if blood glucose levels become too low?

Answer 13

Brain only has access to [BG]

Question 14

Overflow due to problem with glucose metabolism can cause what?

Answer 14

overflow of glucose into urine

Question 15

What is lipogenesis?

Answer 15

excess glucose moves into fat stores

Question 16

What is lipogenesis? what is stimulated by

Answer 16

excess glucose moves into fat stores

stimulated by insulin binding to receptor on fat cell

Question 17

What is glucagon responsible for?

Answer 17

Increasing blood glucose levels - peptide hormone produced by alpha cells of the pancreatic islet cells

Question 18

What is insulin responsible for?

Answer 18

Decreasing blood glucose levels

Question 19

What does the pancreas release through ducts to support digestion?

Answer 19

enzymes

NaHCO3

Question 20

Only 1% of the pancreas has endocrine function. Where are it’s hormones produced?

Answer 20

In the Islets of Langerhans

Question 21

What are the 4 types of Islet cells?

Answer 21

alpha cells produce GLUCAGON

beta cells produce INSULIN

delta cells produce SOMATOSTATIN

F cells produce pancreatic polypeptide (function not really known, may help control of nutrient absorption from GIT.)

Question 22

In what ways does insulin reduce [BG]? (4)

Answer 22

Increases glucose oxidation

Increases Glycogen synthesis

Increases fat synthesis

Increases protein synthesis

Question 23

In what ways does glucagon increase [BG]? (3)

Answer 23

Increases Glycogenolysis

Increases Gluconeogenesis

Increases Ketogenesis

Question 24

What happens during the absorptive state?

Answer 24

Glucose, amino acids and fatty acids enter the blood from the GI tract

Both stimulate insulin secretion but the major stimulus is [BG]

Question 25

What is the only hormone that lowers [BG]?

Answer 25

Insulin

Question 26

What is glucose stored as in liver and adipose tissue

Answer 26

Triacylglycerols

Question 27

What is glucose stored as in liver and muscle

Answer 27

glycogen

Question 28

What is the mechanism by which [BG] controls insulin secretion

Answer 28

High [BG] Metabolism increases ATP increases K-ATP channels (specific to pancreatic B cells) close cell depolarises and calcium channels open Ca2+ entry acts as an intracellular signal Ca2+ signal triggers exocytosis and insulin is secreted

Question 29

What happens to close Ca2+ voltage gated channels and stop insulin secretion?

Answer 29

When [BG] is low, [ATP] is low so KATP channels are open K+ ions flow out removing +ve charge from the cell and hyperpolarizing it, so that voltage-gated Ca2+ channels remain closed and insulin is not secreted

Question 30

Primary action of insulin

Answer 30

Binds to tyrosine kinase receptors on the cell membrane of insulin-sensitive tissues to increase glucose uptake by these tissues. In muscle and adipose tissue, insulin stimulates the recruitment of GLUT4 transporter to the membrane Glucose can then be transported into the cell when insulin stimulation stops then GLUT 4 transporters return to cytoplasm pool the glucose taken up by cells is primarily used for energy

Question 31

Which are the only types of tissue that are insulin dependent?

Answer 31

Muscle and fat (takes up large proportion of body mass - so actually a lot of the body is dependent on insulin) not all tissues require insulin to take up glucose - instead its via GLUT transporters

Question 32

Functions of GLUT1, GLUT2 and GLUT3

Answer 32

GLUT1 + GLUT2 - Basal glucose uptake in many tissues eg brain, kidney and red blood cells. GLUT 3 - B cells of pancreas and liver

Question 33

Liver and glucose uptake

Answer 33

liver is not insulin dependent takes up glucose via GLUT 2 transporters (insulin independent) Glucose enters down conc gradient although insulin has no direct effect on the liver, glucose transport into hepatocytes is affected by insulin status

Question 34

How does insulin status indirectly affect glucose transport into hepatocytes?

Answer 34

after eating, insulin promotes intracellular glucose metabolism so lowering the [glucose]IC this creates a concentration gradient favouring glucose movement into the cells

Question 35

How does the liver release glucose in fasted state (post-absorptive)?

Answer 35

The liver synthesises glucose via glycogenolysis and gluconeogenesis (stimulated by glucagon) this increases [glucose]ic creating a gradient favouring glucose movement out of the cells into the blood.

Question 36

Additional actions of insulin - activation of multiple signal transduction pathways associated with the insulin receptor

Answer 36

Increases glycogen synthesis in muscle and liver. Stimulates 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 and inhibits lipolysis. Inhibits the enzymes of gluconeogenesis in the liver Has a permissive effect on Growth hormone Promotes K+ ion entry into cells by stimulating Na+/K+ ATPase. Very important clinically.*** Diabetes – lose K+ entry? - hyperkalaemia

Question 37

Half life of insulin

Answer 37

5 minutes

Question 38

Where is insulin degraded principally

Answer 38

In the liver and the kidneys

Question 39

What happens once insulin action is complete?

Answer 39

Insulin-bound receptors are internalised by endocytosis and destroyed by insulin protease, some recycled.

Question 40

Stimuli that increase insulin release (5)

Answer 40

Increased [BG] Increased [amino acids]plasma Glucagon - insulin takes up glucose which is created by gluconeogenesis which is stimulated by glucagon vagal nerve activity Other hormones controlling GI secretion and motility

Question 41

Stimuli which inhibit insulin release

Answer 41

low [BG] Somatostatin GHIH Sympathetic alpha 2 effects stress - hypoxia

Question 42

Vagal activity

Answer 42

Vagal activity stimulates release of major GI hormones, and also stimulates insulin release therefore meaning that the insulin response to an IV glucose load is less than the equivalent amount of glucose administered orally (goes through gut)

Question 43

Half life of glucagon

Answer 43

5-10 mins in plasma | degraded mainly by liver

Question 44

What is involved in the glucose counter-regulatory control system

Answer 44

Glucagon Epinephrine Cortisol Growth hormone

Question 45

When is glucagon most active?

Answer 45

Post-absorptive state (between meals/at night)

Question 46

What are glucagon receptors like?

Answer 46

G protein coupled receptors linked to the adenylate cyclase/cAMP system - when activated phosphorylate specific liver enzymes

Question 47

What happens when specific liver enzymes are phosphorylated after glucagon binds

Answer 47

increased glycogenolysis increased gluconeogenesis (substrates: aa’s and glycerol (lipolysis)) formation of ketones from fatty acids (lipolysis)

Question 48

Stimuli that promote glucagon release

Answer 48

Low [BG] (<5mM) high [amino acids] - prevent hypoglycaemia Sympathetic innervation and epinephrine, B2 effect Cortisol Stress - exercise, infection

Question 49

Stimuli that inhibit glucagon release

Answer 49

BG free fatty acids and ketones Insulin somatostatin

Question 50

Autonomic nervous system innervation of islet cells

Answer 50

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

Question 51

Somatostatin (also known as growth hormone inhibiting hormone)

Answer 51

Somatostatin is a peptide hormone secreted by Delta cells of the pancreas Main pancreatic action is to inhibit activity in the GI Tract. It seems to slow down absorption of nutrients to prevent exaggerated peaks in plasma concentrations. SS is NOT a counter-regulatory hormone in the control of blood glucose but it does strongly suppresses the release of both insulin and glucagon in a paracrine fashion.

Question 52

Effect of exercise on [BG]

Answer 52

The entry of glucose into skeletal muscle is increased during exercise, even in the absence of insulin. Exercise also increases the sensitivity of muscle to insulin, and causes an insulin-independent increase in the number of GLUT-4 (on skeletal muscle) transporters incorporated into the muscle membrane. regular exercise can produce prolonged increases in insulin sensitivity critical in improving type 2 diabetes - – exercise lowers BG without requiring insulin

Question 53

Starvation

Answer 53

When nutrients are scarce, body relies on stores for energy – when adipose tissue is broken down fatty acids are released. Free FA’s can be readily used by most tissues to produce energy and liver will convert excess to ketone bodies which provides an additional source for muscle and brain (in extreme cases)! this serves to 'spare protein' as otherwise too much protein would be lost - very weakening, vulnerable to infection

Question 54

After a period of starvation what does the brain do

Answer 54

adapts to be able to use ketones as an energy source

Question 55

How does life- threatening acidocis come about in diabetes type 1

Answer 55

in poorly controlled insulin-dependent diabetes a lack of insulin depresses ketone body uptake (because insulin supports this uptake). They build up rapidly in the plasma and because they are acidic create life threatening acidosis (ketoacidosis or ketosis) with plasma pH < 7.1. (normal = 7.4) Death will occur within hours if untreated.

Question 56

Type 2 diabetes - non-insulin dependent diabetes mellitus

Answer 56

Peripheral tissues become insensitive to insulin = insulin resistance. Muscle and fat no longer respond to normal levels of insulin. This is either due to an abnormal response of insulin receptors in these tissues or a reduction in their number. B-cells remain intact and appear normal, there may even be hyperinsulinaemia. 90% of diabetic patients are of this type

Question 57

Glucose tolerance test

Answer 57

Patient ingests glucose load after fasting [BG] measured. [BG] will normally return to fasting levels within an hour, elevation after 2 hours is indicative of diabetes. Does not distinguish Type I from II. [BG] elevated in both Type I and Type II Diabetes for different reasons: Type 1 - inadequate insulin release Type 2 - inadequate tissue response Hyperglycaemia (elevated [BG]) is the diagnostic criterion for diabetes - detected by GTT

Question 58

Glucose tolerance test

Answer 58

Patient ingests glucose load after fasting [BG] measured. [BG] will normally return to fasting levels within an hour, elevation after 2 hours is indicative of diabetes. Does not distinguish Type I from II. [BG] elevated in both Type I and Type II Diabetes for different reasons: Type 1 - inadequate insulin release Type 2 - inadequate tissue response Hyperglycaemia (elevated [BG]) is the diagnostic criterion for diabetes - detected by GTT

Question 59

Diabetic complications (4)

Answer 59

Retinopathy Neuropathy Nephropathy Cardiovascular Disease