diabetes

Question 1

4 hormones involved in glucose homeostasis

Answer 1

Insulin
Glucagon
Adrenaline
Glucocorticoids ( esp cortisol )

Question 2

Fasting vs fed state

Answer 2

Fed = insulin - glucose to glycogen 
Fasting = glucagon

Question 3

insulin

Answer 3

Signals the fed state

Secreted in response to high blood glucose from B cells of the pancreas

Question 4

Glucagon

Answer 4

Signals the fasting state

Secreted in response to low blood glucose from the alpha cells of the pancreas

Question 5

Adrenalin

Answer 5

Secreted from adrenal medulla in response to low blood glucose an fear, stimualates fuel mobilisation, especially in muscle and adipose tissue

Question 6

Glucocorticoids - cortisol

Answer 6

Secreted in response to stress and starvation
Long term effects on the expression of enzymes involved in fat and carb metabolism
HYDROPHOBIC - cross membranes

Question 7

Hormones derived from cholesterol

Answer 7

Cortisol 
Aldosterone 
Testosterone 
Estrogen 
Progesterone

Question 8

2 types of molecule interaction receptor

Answer 8

Cell surface receptors

Intracellular receptors

Question 9

How do steroid hormones enter the cell

Answer 9

Transported in the blood bound to transporter proteins
Inside cell membrane. they bind to members of the nuclear receptor family
Nuclear receptor signal complexes bind specific DNA sequences and regulate gene expression
As these responses require protein synthesis, timescale is slow

Question 10

Cortisol in central metabolism

Answer 10

Increases fuel supply
Released in response to stress
Stimulates breakdown of non essential muscle tissue into AA for GNG
stress adaptation
Elevates blood pressure, increases NA+ uptake by kidney
Increases expression of hormone sensitive lipase = triglyceride mobilisation

Question 11

Cortisol acts on..

Answer 11

Liver, muscle and adipose tissue

synthesised in fasciculate

Question 12

Prolonged cortisol …

Answer 12

LOOSES positive effect

Causes damage

Question 13

Where are insulin, glucagon and other peptide hormones released from

Answer 13

PANCREAS
alpha cells - glucagon
beta cells- insulin
delta cells - somatostatin

Question 14

What are the pancreatic cells that secrete insulin and glucagon

Answer 14

ISLETS OF LANGERHANS

Question 15

Insulin function and formation

Answer 15

Lowers blood glucose
synthesised as preproinsulin 
Signal sequence directs it to ER 
A and B peptides are linked by disulphide bonds and the proinsulin is cleaved twice by a protease 
INsulin - secretory vesicle

Question 16

Glucagon, cortisol and adrenaline - blood glucose

Answer 16

RAISES

Question 17

Secretory granules

Answer 17

Insulin released

Question 18

2 phases of insulin secretin - BIPHASIC

Answer 18

1st phase = fusion of granules with plasma membrane

2nd phase = synthesis and translocation of granules to the membrane

Question 19

Factors affecting insulin secretion

Answer 19

Adrenaline - inhibitory
Amino acids - stimulatory
fatty acids - stimulatory

Question 20

How does insulin enter cells

Answer 20

Insulin binds to RTK coupled receptor, which activates RTK and auto phosphorylates tyrosines
Phosphorylated receptor can now bind IRS1 allowing PIP2 to be converted into PIP3 ( both embedded in membrane)
PIP3 activates PDK1 which activates Akt
akt activates responses - cells update glucose

Question 21

Pip3

Answer 21

Can be cleaved to become IP3 and DAG - which are also second messengers

Question 22

Insulin signalling pathway

Answer 22

Primary transduction 
relay 
Transduction and amplification 
Feedback 
Distribute 
Altered metabolism

Question 23

Muscle cells and glucose

Answer 23

Have a low Km

if there’s high glucose conc and kM is lower - CANT UPTAKE

Question 24

Muscle and adipose uptake of glucose

Answer 24

GLUT4 trasnporters in vesicles in cell
When insulin binds, Akt activates- vesicles fuse with plasma membrane
Rate of glucose uptake increase 15x more

Question 25

How does glucose regulate insulin secretion from B cells

Answer 25

Glucose enters B cells via GLUT 2 transporter Glycolysis leads to ATP increase ATP binds to ATp gated k+ channels and they close, depolarising the plasma membrane Triggers the opening of voltage gated ca2+ channel s Increased cytosolic triggers more ca2+ release Fromm the ER and this wave of calcium inside the cell triggers insulin secretion by exocytosis

Question 26

ATP gated K+ channels and diabetes

Answer 26

Aolfonylurea drugs such as tolbutamide bind to SUR1 subunits closing the K+ channel stimulating insulin release Diazoxide opens the channel and is used to treat low blood pressure caused by pancreatic tutors over releasing insulin

Question 27

Insulin binding activates

Answer 27

``` Glucose uptake Glycogen synthesis Glycolysis - PSK and PSK2 Pyruvate oxidation Fatty acid synthesis ```

Question 28

Glucagon and adrenaline binds to ..

Answer 28

GPRCs on cell surface Work via adenyl cyclase and cAMP Activate glycogen breakdown

Question 29

Glucagon acts on

Answer 29

Liver, adrenaline on muscle and adipose tissue

Question 30

Adrenaline function

Answer 30

Stimulates glucagon secretion Inhibits insulin secretion Lactate formation Fight or flight

Question 31

Glucagon effect

Answer 31

``` Glycolysis inhibits Gluconeogenesis Protein and fatty acid synthesis inhibited Glycogen breakdown in liver Ketone body synthesis activated ```

Question 32

2 types of diabetes

Answer 32

type I- can't produce or secrete insulin, destruction of beta cells - insulin injection type II- can't respond to insulin - diet and drugs

Question 33

Diagnosis of diabetes

Answer 33

Urine glucose analysis Oral glucose tolerance test Glycated haemoglobin Measurement of plasma insulin

Question 34

HOW DOES THE BRAIN respond to diabetes

Answer 34

Starving state Body Assumes theres no glucose in the blood Gluconeogenesis produces glucose for brain Proteins are broken down and glycogenic aa yield glucose as fuel from brain. NH3 -- urea and excreted Fatty acids produce acetyl CoA used for ketone body production Acetone ( ketone body) exhaled Conc of ketone bodies increases and compounds appear in the urine

Question 35

Diabetes symptoms - both forms

Answer 35

Blood sugar elevated | Body tries to dilute glucose= excessive urine and thirst

Question 36

TYPE I diabetes symptoms

Answer 36

Fat breakdown is accelerated which leads to high production of ketone bodies Some of ketones are ketoacids which raise blood H+ leading to ketoacids Bicarbonate buffering sustem is activated, leading to altered breathing Acetone expelled via breath Untreated diabetes leads to dramatic weight loss

Question 37

What happens when blood sugar levels are elevated

Answer 37

Haemoglobin becomes glaciated Compromises o2 delivery Increases risk of CVD, renal failure and damage to blood vessels

Question 38

Early symptoms of diabetes

Answer 38

Urination, thirst, blurred vision, fatigue, headache

Question 39

Later symtoms od diabetes

Answer 39

``` Pear drop breath ( acetone) Nausea and vomiting Shortness of breath Dry mouth Abdominal pain Weakness Confusion Coma ```

Question 40

Measuring blood glucose

Answer 40

Pinprick monitors Urine test strips - shouldn't be seen in urine if you're well mM concentrated

Question 41

Oral glucose tolerance test

Answer 41

75g of glucose See how the blood glucose conc changes Starts at 5mm, then increases then reduces Diabetic - higher than normal at rest, then goes increasingly higher, slowly slowly decreases

Question 42

Impaired glucose tolerance

Answer 42

Increase then slow decrease | BETWEEN diabetes

Question 43

Measuring insulin

Answer 43

Enzyme linked immunosorbent assay ( ELISA) Insulin is an antigen , coat surface of well with plasma sample , block unoccupied sites with non specific protein, incubate with primary antibody against antiegen and secondary antibody, add substrate, formation of coloured product = insulin , more yellow = more antibody = more insulin