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CBL endocrine > diabetes > Flashcards

diabetes Flashcards

1
Q

4 hormones involved in glucose homeostasis

A

Insulin
Glucagon
Adrenaline
Glucocorticoids ( esp cortisol )

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2
Q

Fasting vs fed state

A 
Fed = insulin - glucose to glycogen 
Fasting = glucagon
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3
Q

insulin

A

Signals the fed state

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

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4
Q

Glucagon

A

Signals the fasting state

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

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5
Q

Adrenalin

A

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

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6
Q

Glucocorticoids - cortisol

A

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

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7
Q

Hormones derived from cholesterol

A 
Cortisol 
Aldosterone 
Testosterone 
Estrogen 
Progesterone
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8
Q

2 types of molecule interaction receptor

A

Cell surface receptors

Intracellular receptors

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9
Q

How do steroid hormones enter the cell

A

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

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10
Q

Cortisol in central metabolism

A

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

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11
Q

Cortisol acts on..

A

Liver, muscle and adipose tissue

synthesised in fasciculate

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12
Q

Prolonged cortisol …

A

LOOSES positive effect

Causes damage

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13
Q

Where are insulin, glucagon and other peptide hormones released from

A

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

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14
Q

What are the pancreatic cells that secrete insulin and glucagon

A

ISLETS OF LANGERHANS

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15
Q

Insulin function and formation

A 
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
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16
Q

Glucagon, cortisol and adrenaline - blood glucose

A

RAISES

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17
Q

Secretory granules

A

Insulin released

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18
Q

2 phases of insulin secretin - BIPHASIC

A

1st phase = fusion of granules with plasma membrane

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

19
Q

Factors affecting insulin secretion

A

Adrenaline - inhibitory
Amino acids - stimulatory
fatty acids - stimulatory

20
Q

How does insulin enter cells

A

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

21
Q

Pip3

A

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

22
Q

Insulin signalling pathway

A 
Primary transduction 
relay 
Transduction and amplification 
Feedback 
Distribute 
Altered metabolism
23
Q

Muscle cells and glucose

A

Have a low Km

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

24
Q

Muscle and adipose uptake of glucose

A

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

25
Q

How does glucose regulate insulin secretion from B cells

A

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

26
Q

ATP gated K+ channels and diabetes

A

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

27
Q

Insulin binding activates

A 
Glucose uptake 
Glycogen synthesis 
Glycolysis - PSK and PSK2 
Pyruvate oxidation 
Fatty acid synthesis
28
Q

Glucagon and adrenaline binds to ..

A

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

29
Q

Glucagon acts on

A

Liver, adrenaline on muscle and adipose tissue

30
Q

Adrenaline function

A

Stimulates glucagon secretion
Inhibits insulin secretion
Lactate formation
Fight or flight

31
Q

Glucagon effect

A 
Glycolysis inhibits 
Gluconeogenesis 
Protein and fatty acid synthesis inhibited 
Glycogen breakdown in liver 
Ketone body synthesis activated
32
Q

2 types of diabetes

A

type I- can’t produce or secrete insulin, destruction of beta cells - insulin injection

type II- can’t respond to insulin - diet and drugs

33
Q

Diagnosis of diabetes

A

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

34
Q

HOW DOES THE BRAIN respond to diabetes

A

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

35
Q

Diabetes symptoms - both forms

A

Blood sugar elevated

Body tries to dilute glucose= excessive urine and thirst

36
Q

TYPE I diabetes symptoms

A

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

37
Q

What happens when blood sugar levels are elevated

A

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

38
Q

Early symptoms of diabetes

A

Urination, thirst, blurred vision, fatigue, headache

39
Q

Later symtoms od diabetes

A 
Pear drop breath ( acetone)
Nausea and vomiting 
Shortness of breath 
Dry mouth 
Abdominal pain 
Weakness
Confusion 
Coma
40
Q

Measuring blood glucose

A

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

41
Q

Oral glucose tolerance test

A

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

42
Q

Impaired glucose tolerance

A

Increase then slow decrease

BETWEEN diabetes

43
Q

Measuring insulin

A

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

CBL endocrine (8 decks)

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