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BIOL1013 > Endocrinology > Flashcards

Endocrinology Flashcards

1
Q

What two factors will effect metabolism?

A

Genetics and environmental factors

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2
Q

Draw a tree diagram to show how those two actors effect metabolism

A
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3
Q

Where is growth hormone secreted from?

What responds to it?

A

Release from somatotrope anterior pituitary cells induced by GHRH (inhibiter somatostatin GHIH)

does not act through a specific endocrine gland as other tropins rather almost all tissues respond to it especially the liver.

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4
Q

What effects does the secretion of GH cause?

What does this result in?

A
  • protein production
  • cell size
  • cell division

results in tissue grwoth e.g. muscle mass and bone growth

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5
Q

What does GH induce?

Whats the main cause of GH activity?

A
  • GH Induces expression of somatomedins, Insulin Like Growth Factor 1- there are other but this one is turned on by GH (IGF-1) by liver
  • main cause of GHs activity as IGF-1has long half life
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6
Q

What response is caused by the expression if IGF-1 ?

A
  • Increases cartilage and bone growth
  • Increases amino acid uptake into cells
  • Increases RNA transcription and translation (protein production)
  • Lower protein catabolism (raises blood AAs)
  • Increases lipid breakdown (causes raised blood FFAs)
  • Decreases carbohydrate metabolism (causes raised blood glucose)
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7
Q

Tell me some general facts of GH?

A
  • use lipids
  • make- and general tissue use less- glucose
  • save and produce protein/ AAs
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8
Q

What does the GH somatotropin stimulate?

A
  • GH is secreted in starvation in order to prevent you using protein
  • Infection also increases GH
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9
Q

What reduces GH secretion ?

A
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10
Q

What is altered in order in increase or decrease GH?

Name two hypothalamic hormones which help do this?

A

these act to be altering hypothalamic tropic hormones

hypothalamic hormones

  1. Growth hormone-releasing hormone (GHRH)

2 .Growth hormone inhibitory hormone (somatostatin) (GHIH)

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11
Q

Name a downstream control of the GH?

What feedback loop is it?

A

Somatomedins (IGFs- negative feedback)

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12
Q

What are somatostatin also secreted by?

A

delat cells at several locations in the digestive system

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13
Q

Draw the flow diagram from the hypothalamus to IGF-1 release ?

A
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14
Q

The flow diagram as drawn above is a complex regulation system and can lead to loss of responsiveness due to defects at different points. what can this lead to?

A
  • failure in production of hormone
  • Failure in response to hormone (pituitary targets)
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15
Q

What can increased GH signalling lead to?

A

Abnormal repsonses at these points

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16
Q

Whats a growth plate?

A

The area of growing tissue near the end of long bones in children and adolescents.

Each long bone has at least two growth plates, one at each end

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17
Q

Increased GH can lead to growth defects such as…

A
  • Acromegaly
  • Giantism
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18
Q

How do thyroid gland hormones alter metabolism?

A
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19
Q

Tell me about the thyroid stimulating hormone and what it binds to ?

A
  • 3 AA long
  • binds to receptors on thyroid follicle gland
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20
Q

What does T3 and T4 mean?

A

T3 means 3 iodine groups

T4 means 4 iodine groups

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21
Q

Whats Thyroglobulin?

What does it release and how?

A

A tyrosine rich store, which is iodinated, reabsorbed and broken down by proteases in lysosomes to release T3 and T4

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22
Q

What is TSH/ thyrotropin released in response to?

A

cold via action of TRH

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23
Q

What are the actions of TSH?

A
  • Increases number, sizes and activity of cuboidal epithelia in the thyroid gland
  • Increases iodide pump
  • Increases enzymes for iodination of tyrosine
  • Increases thyroglobulin proteolysis
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24
Q

Give an example of a tropic and trophic hormone?

A

TSH

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25
Q

Draw the structures of T3 and T4

The percentage released from the gland

Thyroxine binding globulin attachment

A
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26
Q

If thyroxine is injected, when does it have its effect?

A

About 10 days later

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27
Q

Where is T4 mainly broken down?

A

In the plasma (loses iodine) so cells mainly see T3

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28
Q

Tell me the half life of T3 and T4

A

T4 half life: 6 days

T3 half life: one day

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29
Q

Why is T3 more active

A

Less well bound by binding proteins (in end T3 is 90% of intracellular action)

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30
Q

Tell me what T3 and T4 bind to and what this activates?

A

Binds to thyroid receptor (nucleus) which then binds Retinoid X Receptor (RXR), activates transcription

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31
Q

Tell me the effects T3 and T4 has on basal metabolic rate

A
  • Increases basal metabolism in almost all tissues
  • Increases number and size and activity of mitochondria
  • Increase cells leakiness to Na+ –> increases heat production (Na/K/ ATPase more active)
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32
Q

How does T3 and T4 effect carbohydrate metabolism?

A
  • stimulates it
  • increases glucose uptake, its production from other metabolites AND its breakdown
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33
Q

How is T3 and T4 involved in fat metabolism?

A
  • stimulates it
  • mobilises lipids from adipocytes
  • increases beta-oxidation
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34
Q

How does T3 and T4 affect protein synthesis in development ?

A
  • stimulates it
  • increases growth of long bones
  • in foetal and early life it induces CNS development
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35
Q

Tell me some main facts about T3 and T4?

A
  • Use lipids
  • Make and use glucose
  • save and produce proteins
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36
Q

Tell me some effects of hyperthyroidism?

A
  • Weight loss
  • Sleep less
  • exophthalmos (ulcers as dries in sleep)
  • tremble due to increase nervous activity
  • can be tumours
  • feel hot
  • weakening of eye muscles
  • Stimulatory autoimmune disease on thyroid
  • if AutoImmune – inflammation of periorbital fat (Graves Diseases)
  • (primary in thyroid, secondary in pituitary) or AI disease with antibodies not killing but stimulating the gland by activating TSH receptors
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37
Q

Tell me some effects of hypothyroidism?

A
  • AI but with destruction of gland
  • I2 deficiency
  • (goitre) myxoedema: watery collection in tissues
  • hyaluronic acid/ chondroitin layer in wrong place
  • gain Weight
  • Sleep more
  • Not stimulatory autoimmune disease
  • Cretinism: mental retardation if have an iodine deficient diet
  • Feel cold
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38
Q

What does ACTH regulate?

A

The amount of cortisol in the adrenal cortex

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39
Q

MISTAKE FROM PREVIOUS LECTURE, THIS IS THE RIGHT STATEMENT

There is Less T3 then T4 and most T4 binds to carrier protien

A
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40
Q

What are the layers of the adrenal gland from inside to out?

A

Inside

Medulla

Cortex which has the 3 layers:

Zona reticularis

Zona fasciculata

Zona glomerulosa

outside

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41
Q

Tell me the hormones released and an example produced from each tissue area of the drenal gland

A
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42
Q

Tell me 6 examples of steroid hormones (all steroids are based on cholesterol from the membrane)

A
  1. Oestrogens
  2. Progesterone’s
  3. Androgens (testosterone)
  4. Glucocorticoids (cortisol)
  5. Mineralocorticoids (aldosterone)
  6. Vitamin D
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43
Q

What does the site of adrenal steroid hormone production depend on?

A

The enzymes in that zone

e.g. mineralocorticoid produced in zona glomerulosa depends on the aldosterone synthetase

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44
Q

Tell me about the synthesis of steroid hormones?

A

They are synthesised only when needed, with immediate secretion

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45
Q

Why can’t steroids be stored in the cell?

A

They are highly lipophilic

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46
Q

Tell me the secretion rates of adrenal steroids in mg/day

A
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47
Q

Tell me the relative potencies of steroids

give the glucocorticoids effect

give the mineralocoritcoid effect

These are the following steroids:

  1. cortisol
  2. corticosterone
  3. aldosterone
  4. cortisone
  5. dexamethason
A
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48
Q

Which steroids are synthetic?

What are they used for?

How are they commonly applied?

A

Cortisone and dexamethasone are synthetic

they are used for anti-inflammatory effects

Dexamethasone is an artifical corticosterone and this tends to be injected

Cortisone can be used as a cream

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49
Q

What do ACTH signals increase?

A

The uptake of cholesterol and debranching of cholesterol to prednisone in the adrenal

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50
Q

Draw the reaction of the formation of corticosterones and cortisol from cholesterol and where ACTH regulates activity and where it induces expression

A

ACTH regulates the levels of cortisol being produced

(dont need to know about the changes in side chains)

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51
Q

Tell me about the glomerulosa layer

A
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52
Q

Tell me 2 stimuli for cortisol release

A
  • circadian rhythm
  • stress
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53
Q

Where are the following hormones produced and tell me the reaction for secretion of CRH-ACTH-cortisol release?

A
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54
Q

When are peaks in cortisol seen?

A
  • when you first wake up
  • another peak from physical or emotional stress
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55
Q

What is ACTH used as?

A

A precursor hormone in pituitary gland

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56
Q

what does stress increase release?

A

20-30 fold, pain acts via CRF/H

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57
Q

What cells express prohormone convertase 1 (not 2) so only these make what?

A

Only pituitary corticotrope cells express prohormone convertase 1 and (not 2) so only these make ACTH from precursor

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58
Q

What are the controls for glucocorticoids secretion?

What feedback loop is this?

A

Negative feedback controls for glucocorticoids

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59
Q

Whats the mechanism of adrenocorticoids action?

A
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60
Q

What are the 3 functional domains of steroid hormone receptors?

A
  1. Ligand-binding domain: C-terminal, Ligand-dependent nuclear translocation signal, Chaperone (inhibitory) protein binding domain
  2. DNA-binding domain: 2 Zn finger motifs (central area of receptor)
    1. Ligand-dependent transcription activating domain (recruit’s transcriptional co-activators
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61
Q

Tell me the steps to the activation of intracellular receptors?

A
  1. steroid shows cytosolic binding
  2. complex migrates to nucleus
  3. (cf- thyroid hormone receptors are nuclear)
  4. hormone binding changes conformation (shape) of the receptor protein
  5. causes inhibitory protein complex to dissociate and opens up nuclear translocation signal region- receptor/ hormone complex transfers to nucleus
  6. causes the receptor to bind to coactivator proteins that induce gene transcription
  7. Receptor activation induces the modulation of transcription of specific genes that have hormone receptor elements (HRE).
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62
Q

What are HREs?

A

Are short cis-acting sequences located within the promotors or enhancers of target genes

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63
Q

Give 2 examples of steroid hormones HREs

A
  1. inverted repeats of AGGTCA (oestrogen receptor)
  2. Inverted repeats of AGAACA (glucocorticoids receptors)
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64
Q

How is specificity of intracellular receptors given?

A
  • which cells express the receptor
  • which cells express the coactivator
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65
Q

What is glucocorticoid secretion dependant on?

A

CRH –> ACTH –> Cortisol

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66
Q

Where is glucocorticoids found?

A

They circulate the plasma and are most bound to transcortin (corticosteroid-binding globulin)

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67
Q

Tell me about the unbound glucocorticoids ?

A

unbound: 5-8% of total cortisol (biologically active)

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68
Q

When unstressed when is peak plasma cortisol and ACTH seen?

A

around 7am, just before waking

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69
Q

What do glucocorticoids drive and what is this?

A

They drive catabolism.

This is a metabolic pathway that break down molecules into smaller units and release energy

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70
Q

how do Glucocorticoids cortisol (corticosterone) prevent hypoglycaemia?

A

Spares general use of glucose and glycogen (saved for CNS and RBCs)

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71
Q

What do corticosterone cause the utilisation of?

A

Proteins and fats

overall catabolic (breakdown) function

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72
Q

Where is gluconeogenesis initiated?

A

in the liver

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73
Q

What does gluconeogenesis lower?

A

The use of glucose by cells which causes raised blood glucose

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74
Q

When is adrenal diabetes caused?

A

If there is an excess production of cortisol

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75
Q

What is cortisol needed for?

A

Full activity of glucagon and adrenaline (this helps to prevent hypoglycaemia)

76
Q

How are corticosterones involved with proteins

  • What do they help to reduce?
  • What does it increase?
  • What does it mobilise?
A
  • Reduces protein content of all tissues except liver –needed liver for gluconeogenesis
  • increases protein catabolism and lowers synthesis (e.g. collagen in bones and skin
  • Mobilises amino acids from cells (especially muscle)
77
Q

How are corticosterones involved with lipids?

A
  • increased utilisation /mobilisation of fatty acids for fuel
  • loss from dermis and deposition into head and chest
78
Q

Do corticosterones increase or decrease appetite?

A

increase

79
Q

Tell me the basis of corticosterones?

A
  • Overall catabolic (breakdown) functions
  • Utilisation of proteins and fats
  • Prevents hypoglycaemia
  • Spares general use of glucose/glucogen (saved for CNS and RBC)
80
Q

What effect does glucocorticoids have?

A

Very potent anti-inflammatory effects (hydrocortisone)

81
Q

How do glucocorticoids reduce inflammation/ act as immunosuppresants?

A
  • Stabilises capillary membranes
  • Reduces release of lysosomal enzymes by WBCs
  • Reduces WBC migration
  • Suppressed lymphocyte division
  • Lysis of lymphocyte
82
Q

Tell me how cortisol/ corticosterone prepare a medium/ long term response of the body to stress?

A
83
Q

The hypersecretion by adrenal glands is due to what?

A

High glucocorticoids

‘Cushing’s disease’

84
Q

What does the hypersecretion of adrenal gland cause?

A
  • secondary to hypothalamic tumour (increased CRH)
  • secondary to pituitary adenomas (increased ACTH)
  • primary tumour in adrenal cortex
85
Q

Whats iatrogenic increase?

A

When you’ve been treated with steroids (cushing disease caused by a person being given too much steroids)

86
Q

Tell me some symptoms of cushings disease…

A
  • High blood glucose- increased drinking/ urination
  • Protein loss and muscle weakness
  • Mobilisation of fat

body shape change (due to muscle conversion)

  • Enhances appetite

greatly (fat deposition – even though more is used)

  • Immunosuppressed
87
Q

What is mineralocorticoids produced by?

what indirectly regulates its levels?

What absorption is it involved in?

What does it modify and how?

A
  • Produced by Zona glomerulosa ACTH needed for secretion but Angiotensin II regulates levels
  • NaCl resorption
  • Water resorption
  • K + ions loss
  • Very important (cf High extracellular K+ )
  • Modifies blood pressure by increasing extracellular volume by increasing absorption of NaCl and also water with it
  • NaCl is balanced by K+ loss
88
Q

Whats the most potent mineralocorticoid?

Whats its function?

A

Aldosterone

function: loses K/ retains Na+/ increases BP

89
Q

Where is the receptor of aldosterone found?

A

In the distal convoluted tubule and in the collecting duct

90
Q

Does aldosterone have a carrier protein?

What does this mean?

A

No carrier protein, so rapidly cleared from plasma (shorter action, lower half life than cortisol)

91
Q

What does aldosterone increase the expression of?

A
  • apical membrane Na+ channels
  • luminal/basal Na/K/H pumps.
  • Metabolism

increases Na+ and water resorption and lose of K+ and H+ ions

92
Q

Tell me about the speed of function of aldosterone?

A

Relatively slow (~30 mins) acts through transcription pathway (cf ADH’s G proteins /cAMP pathway, therefore ADH is faster as is already located where needed)

The regulation of K+ in the blood is most important in this process

93
Q

What are the two ways aldosterone release is regulated?

A
  1. Renin-angiotensin-system stimulatory
  2. Atrial Natriuretic factor/hormone (ANF/ANH) Inhibitor
94
Q

Tell me about the Renin-Angiotensin-system

A
  • Low blood pressure detected by the Juxta glomerular (JG) cells: these are modified smooth muscle cells
  • Low Na+ / High K+ in fluid in DCT due to low filtration (low BP) stimulates Macula densa which activates the JG cells
95
Q

What do JG cells release into the blood and what does this cleave?

A

JG cells release Renin into the blood, which cleaves

Angiotensinogen (liver) –> Angiotensin1

96
Q

What is Angiotensin 1 converted to and by what?

What does the product of the above reaction cause?

A
  • Angiotensin 1 converted to Angiotensin 2 by the ACE (Angiotensin-converting-enzyme) on lungs and kidney endothelial cells
  • Angiotensin 2 causes vasoconstriction and adrenal zona glomerulosa to secrete aldosterone (corticosterone –> aldosterone)
97
Q

What is High BP monitored by?

What is produced?

What does it block?

A

Atrial muscle (expansion), which produces ANF-blocks renin formation

98
Q

What does Atrial Natriuretic Factor/hormone (ANF/ANH) lower?

A

lowers Na+ / water reabsorption and hence blood pressure

99
Q

Where is corticotropin releasing hormone released from?

A

They hypothalamus

100
Q

Where is the adrenocorticotropic hormone released from?

A

The anterior pituitary gland

101
Q

Tell me about the role of ACTH?

A

ACTH needed but doesn’t regulate levels of aldosterone, only acting as an on/ off switch. Levels of aldosterone are dependent on levels of renin coming into blood.

102
Q
A
103
Q

What is the failure of adrenal cortex usuaully due to?

give an example?

A

Autoimmune disease (antibodies damage all cortical cells)

e.g. Addision’s disease

104
Q

Tell me two effects of Addisons disease?

A
  • reduced aldosterone
  • reduced glucocorticoids
105
Q

Tell me the effects of reduced aldosterone

A
  • loss of Na+ into urine
  • increased K in extracellular fluids
  • fluid loss
  • muscle weakness
  • if untreated death due to cardiac arrhythmias
106
Q

Tell me about effects of reduced glucocorticoids?

A
  • cannot respond to stress
  • often not diagnosed till stressed e.g. at surgery
  • also increase in ACTH as feedback lost (so more POMC the ACTH precursor formed)
107
Q

What is the normal blood glucose level?

A

70-90 mg/100 ml blood

108
Q

once a meal is eaten, what does the blood glucose level rise to?

A

Increases to 120mg/100mls in the hour after a meal, but generally maintained between meals and during starvation

109
Q

What occurs in the liver-blood glucose buffer system?

A
  • a glycogen store
  • neoglucogenesis centre
  • ketone body former
110
Q

What does insulin and glucagon act as?

A

A fine control centre for glucose concentration act with the higher (stress) responses to regulate blood sugar

111
Q

What hormone does short term hypoglycaemia produce?

A

nor/adrenaline

(sympathetic system and adrenal gland)

112
Q

What hormone does long term hypoglycaemia produce?

A

growth hormone/ cortisol

this induces fat utilisation

113
Q

Tell me what can occur at different blood glucose levels as it drops?

A
114
Q

Fed state means more insulin, what does this increase?

A
  • glucose oxidation
  • glycogen synthesis
  • fat synthesis
  • protein synthesis
115
Q

Fasted state means more glucagon, what does this increase?

A
  • glycogenolysis
  • gluconeogenesis
  • ketogenesis
116
Q
A
117
Q

In the krebs cycle, where does acetyl CoA come from?

A

Glucose or lipids but for this cycle to work you need oxaloacetate

(fat burns in carbohydrate flame)

118
Q

When starving, what does the liver convert FA to?

A

ketone bodies- a way of transferring C2 to other organs

119
Q

Once acetone is made can it be reused?

A

No

120
Q

Name 3 ketone bodies used when fatty acids are oxidised?

A
  • beta hydroxybutyrate
  • Acetoacetate –> acetone
  • acetoacetyl CoA
121
Q

What is glucose needed by?

A
  • brain
  • gonads
  • RBC
122
Q

How are glucose levels maintained between meals?

A

glucose levels maintained between meals first by glycogen breakdown and then by gluconeogenesis

123
Q

If glucose is too low in blood, then what happens

A

Use lipids for energy gives ketone body production in liver, these are energy sources (not acetone) but cause lowering of pH (ketoacidosis- metabolic acidosis)

124
Q

If glucose is too high in the blood, what happens?

A

Glucose lost into urine, if too high it overcomes resorptive capacity of kidney - this carries water and electrolytes with it. (osmotic diuresis)- dehydration

125
Q

What does long term raised blood sugar induce?

A

metabolic changes in many cells especially endothelia increased and abnormal ECM (fibrosis and glycation) and deposition of cholesterol causes

126
Q

What does the deposition of cholesterol cause?

A
  • vascular disease
  • heart attack
  • renal fibrosis
  • retinal degeneration
  • peripheral vascular loss
127
Q

What was insulin isolated by?

A

Banting and Best, 1922

128
Q

What does insulin induce?

A
  • formation of glycogen or (when stores in liver and muscle full) fat
  • induces uptake of amino acids, formation of proteins and inhibits their breakdown
129
Q

What does insulin control?

A

Insulin controls glucose levels, regulating carbohydrate metabolism—but loss leads to abnormal use of fats –> acidosis, atherosclerosis and use of proteins and hence wasting

130
Q

What is insulin formed by?

What is insulin degraded by?

A

Formed from: Beta cells in islet of langerhans

Degraded by: serum insulinase especially in liver

131
Q

What is glucose monitored by?

What does it express?

A

Glucose is monitored by beta cells

express GLUT2 transporters (not insulin dependent)

132
Q

What increases insulin secretion?

A
  • Increased blood glucose
  • Increased blood free fatty acids
  • Increased blood amino acids
  • Gastrointestinal hormones (gastrin, cholecystokinin, secretin)
  • Glucagon, growth hormone, cortisol (all increase blood glucose- insulin induces uptake)
133
Q

What do high levels of glucose lead to?

A

increased ATP formation which closes the ATP gates K+ channels

  • cellular depolarisation as Na+ still enters cell and opening of Ca2+ channels
134
Q

Exocytosis of insulin containing vacuoles

A
135
Q

What decreases insulin secretion?

A
  • Decreased blood glucose (fasting)
  • Alpha-adrenergic activity (acute stress- low insulin saves uptake for CNS)
136
Q

Tell me about Class 1 RTKs?

A

(receptor tyrosine kinases)

They come together on ligand binding

137
Q

Tell me about class 2 RTKs?

A

Disulphide linked tetramers, remain together continually

138
Q

Tell me about the Insulin receptor structure?

A

Has two alpha and beta subunits which are disulphide linked into alpa2beta2 heterotetrametric

139
Q

What do the extracellular alpha subunits of the insulin receptor contain?

A

The insulin binding domains

140
Q

What do the transmembrane beta insulin receptors contain?

A

The tyrosine kinase domains

141
Q

The auto/cross phosphorylation of the beta subunits of insulin receptors induces what?

A

The docking of downstream signalling proteins

142
Q

Ligand binding does not cause class 2 RTKs to dimeriza but what does it do?

A

It brings the two beta subunits closer to phosphorylate each other

143
Q

What are the effects of insulin signalling?

A
  1. very rapidly induces fusion of intracellular vacuoles with the cell surface, these carry the insulin dependent glucose transporter-facilitated transfer of glucose
  2. activation of intracellular enzymes needed for glycogen production (slower)

increase in gene expression (slowest)

144
Q

the induced fusion of intracellular vacuoles with the cell surface, carry insulin dependent glucose transporters.

What are these cell membranes permeable to?

These occurs in what cell types?

A
  • permeable to amino acids (AA transporters also in these vacuoles)
  • Occurs most in; RBCs, neurons, Beta-pancreatic cells

(have non-insulin dependent glucose transporters need glucose all the time)

145
Q

The transfer of glucose and AA transporters to the plasma membrane

A
146
Q
A
147
Q
A
148
Q

What uptake does insulin induce?

What happens to it?

A

Insulin induces glucose uptake, it is used or stored either as glycogen or lipid

149
Q

What do carbohydrates induce?

A

glycogen storage in muscle and liver after a meal

150
Q

formation of carbs. activates hepatic glucokinase, what does this trap?

A

absorbed glucose within the cell

151
Q

When glycogen is made from carbs. what is maintained?

A

active glycogen synthetase

152
Q

What keeps glycogen?

A

inactivates hepatic glycogen phosphorylase

153
Q

What do carbs. promote?

A

The conversion of excess glucose to fatty acids ?

154
Q

What do carbs. inhibit?

A

gluconeogenesis

155
Q

Whats happens overall from carbs?

A

glucose is preferentially used after a meal- as preferential energy source or store

156
Q

What does insulin promote?

A

fat synthesis and storage

157
Q

In the liver, what does lipid formation promote?

A
  • promotes glucose use -so saves lipids breakdown
  • excess glucose uptake in liver converted to acetyl CoA used to form fatty acids.
  • liver fatty acids released as triglycerides (VLDL) to be reabsorbed by adipocytes
158
Q

what do lipids in adipocytes inhibit?

A

inhibits hormone (catecholamine) sensitive lipase (lowers lipid breakdown)

159
Q

What happens overall when lipids are formed?

A

Overall - Lowered use of lipids to provide energy and increase in their formation

160
Q

What does insulin promote is proteins?

A
  • protein formation and storage
  • uptake of AA into cells
161
Q

What do proteins increase?

A

Increases gene transcription/ translation (especially genes promoting lipid and carbohydrate formation)

162
Q

What do proteins inhibit?

A

Inhibits protein catabolism/ gluconeogenesis

163
Q

How does insulin increase growth in proteins?

A

insulin works synergistically with growth hormone to increase growth

164
Q

What happens overall with proteins?

A

Overall – increased protein production, reduced breakdown— growth

165
Q

What are the actions of insulin?

A
166
Q

What is glucagon produced by and what does it induce?

A

Produced by alpha cells

induces glycaemia (increased blood sugar levels)

167
Q

When is glucagon released?

A

Release is caused by low blood glucose (initiated at < 80-90mg/glucose/ 100ml blood)

168
Q

What does low blood sugar in alpha cells lead to?

A

low blood glucose leads to low ATP in alpha cells - ATP depended K channels close

  • leads to depolarisation- and opening of voltage gated Na channel
  • results in further depolarisation and voltage gated Ca channels opening
  • allowing vesicle fusion and glucagon release
169
Q

The following diagram shows the signalling pathway in the liver

A

Highly amplified system 5-10micrograms glucagon can double blood glucose in minutes

170
Q

What does glycogenolysis in the liver increase?

A

Glycogenolysis in liver increasing blood glucose (opposing insulin)

171
Q

What does the presence of glucagon cause?

A

Causes gluconeogenesis, liver forming glucose from amino acids (opposing insulin)

172
Q

What does glucagon increase in the liver?

What are the amino acids in insulin and glucagon used for?

A

Increases amino acid uptake by the liver (like insulin). But …

insulin– amino acids used for growth

glucagon– amino acids used for energy

173
Q

Does raised blood sugar after a meal inhibit or stimulate glucagon expression?

A

Raised blood sugar after a meal inhibits glucagon expression- and vice versa

174
Q

Very high serum amino acids increases what?

A

Very high serum amino acids, increases glucagon expression

after a very high protein meal acts to increase uptake and convert amino acids to glucose (job is to maintain glucose levels)

175
Q

Does exercise increase or decrease levels of glucagon?

why?

A

Exercise increases levels glucagon (in preparation for glucose debt)

176
Q

In diabetes, what is there a failure of?

A

A failure in water reabsorption in the kidneys collecting duct

177
Q

An excess of glucose in blood leads to what?

A

Osmotic diuresis

178
Q

What does insipidus mean?

A

without taste

179
Q

What does mellitus mean?

What does it lead to?

A

Means sweet taste

causes:

  • adrenal diabetes
  • insulin failure
180
Q

What does adrenal diabetes cause?

A

Cushing’s disease

High glucocorticoids causes raised blood glucose

  • Pregnancy- Gestational Diabetes (see later- also high glucocorticoids)
181
Q

Diabetes mellitus is an insulin signalling failure

What are the two forms of diabetes?

What causes each?

A

Type 1 (insulin-dependent)

  • a lack of insulin secretion
  • combination of genetic and environmental factors
  • normally an autoimmune disease

Type 2 (non-insulin-dependent)

  • failure to respond to insulin “insulin resistant”
  • reduced response when receive insulin
  • long term raised blood glucose due to diet and insulin signalling pathway has turned off because of this
182
Q

The results of diabetes is a lack of utilisation of glucose by all cells except what?

What does this result in?

A

neurones and RBCs

This results in overutilization of lipids and Proteins i.e. metabolically acting as if starving but not

183
Q

Who is type 1 and type 2 diabetes usually found in?

A

Type 1-

  • caused by auto-immune attack upon beta cells
  • often occurs rapidly in teenagers

Type 2

  • increased insulin levels observed with high energy diets, resulting in progressive loss of response to the hormone.
  • Typically, in middle aged obese “metabolic syndrome”-a slow onset syndrome obese, insulin resistance, hyperglycaemia,->hypertension
184
Q

What are the signs of diabetes ?

A
  • High blood glucose
  • Urine contains glucose-(seen when blood glucose is over 180mg/100mls blood)
  • osmotic diuresis- polyuria- dehydration àincreased thirst
  • ketone bodies are osmotically active which makes dehydration worse
  • Use of proteins and lipids as metabolic fuels as glucose and AAs not taken in cells
185
Q

What can diabetes lead to?

A
  • increased appetitie
  • wasting
  • metabolic acidosis: as lipid converted to ketone bodies (acetone breath)
  • Fibrosis: due to long term hypoglycaemia and changes in endothelial cell ECM caused by glycation
  • neuropathy
  • hypertension
  • atherosclerosis- CV disease
186
Q

What are the incidences of type 1 and type 2 diabetes?

A

Type1

1-30 new cases 100,000 per year (highest is Scandinavia?)

Type 2

UK 3,800,000 – i.e. about 1 in 20 diagnosed – true number is believed to be twice that a minimum of 10%

BIOL1013 (9 decks)

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