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JL Endocrinology > Week 1 > Flashcards

Week 1 Flashcards

1
Q

What system consists of ductless endocrine glands that occur at numerous locations in the body?

A

Endocrine system

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2
Q

In the endocrine system - how is communication between glands and other tissues achieved?

A

By secretion of a hormone into blood stream and transport to a target site

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3
Q

Name three things that the endocrine system regulates?

A
  1. Nutrient metabolism
  2. H2O and electrolyte balance
  3. Red blood cell production
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4
Q

What stress hormone is long term and what is short term?

A

Long term - cortisol

Short term - Adrenaline

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5
Q

What are the three main classes of hormones?

A
  1. Glycoproteins and peptides
  2. Steroids - derived from cholsterol
  3. Tyrosine and tryptophan derivatives
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6
Q

Give two hormones in the protein and peptide class?

A

Oxytocin

Insulin

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7
Q

What is tyrosine enzymatically converted to?

A

Adrenaline

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8
Q

How are amines transported in plasma?

A

Freely - they are hydrophilic

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9
Q

What are peptides and proteins pre-synthesised from?

A

Longer precursor

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10
Q

With steroids - what is cholesterol converted to?

A

Pregnenolone - rate limiting step

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11
Q

How are steroids transported in the plasma?

A

Mainly bound to plasma proteins - hydrophobic

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12
Q

Are steroids and thyroxine soluble or insoluble in plasma?

A

Insoluble

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13
Q

Give two roles of carrier proteins?

A
  1. Increase amount transported in blood

2. Prevent rapid excretion by preventing filtration at kidneys

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14
Q

What does sex steroid-binding globulin bind to?

A

Testosterone and estradiol

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15
Q

What does albumin bind to?

A

Steroids and thyroxine

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16
Q

What does transthyretin bind to?

A

Thyroxine and some steroids

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17
Q

What helps to maintain a constant concentration of free lipophilic hormone in the blood?

A

Carrier proteins

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18
Q

Are free and bound hormones in equilibrium?

A

Yes`

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19
Q

What is the primary determinant of plasma concentration?

A

Rate of secretion

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20
Q

What does ‘tropic’ refer to?

A

A hormone that acts upon another endocrine gland to regulate its secretion of hormone

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21
Q

What secretes corticotropinreleasing hormone?

A

Hypothalamus

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22
Q

What does CTRH target which then releases Adrenocorticotropic hormone?

A

Anterior pituitary

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23
Q

What does ACTH act on which then secretes cortisol?

A

Adrenal cortex

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24
Q

Hormone receptors exist as three structurally and funtionally distinct types - name the two cell surface receptors and the one intracellualr receptor?

A

GPCR
Receptor kinases

nuclear receptors

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25
Q

What are class 1 nuclear receptors activated by?

A

Steroid hormones

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26
Q

What are class 2 nuclear receptors activated by?

A

Lipids

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27
Q

What are hybrid class nuclear receptors activated by?

A

Thyroid hormone

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28
Q

What type of receptor is this: binding of insulin causes autophosphorylation of intracellular tyrosine residues. recruitment of multiple adapter proteins, notibly IRS1, that are also tyrosine phosphorylated?

A

Receptor kinases

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29
Q

What are nuclear receptors?

A

Ligand-gated transcription factors

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30
Q

What four cells are in pancreatic islets - in order of most abundant first?

A
  1. Beta-cells
  2. Alpha-cells
  3. Gamma-cells
  4. PP cells
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31
Q

What do beta-cells secrete?

A

Insulin

32
Q

What do alpha cells secrete?

A

Glucagon

33
Q

What do gamma cells secrete?

A

Somatostatin

34
Q

What do PP cells secrete?

A

Pancreatic polypeptide

35
Q

What is synthesised in the rough ER of pancreatic beta-cells as a larger single chain preprohormone - preprosinsulin?

A

Insulin peptide

36
Q

During secretion of insulin: how does glucose enter beta-cells and what phosphorylates it>

A

GLUT2 glucose transporter

Glucokinase

37
Q

What phosphorylates glucose at very low concentrations?

A

Hexokinase

38
Q

What does an increased metabolism of glucose lead to in relation to intracellular ATP concentration>

A

An increase

39
Q

In relation to insulin secretion: what does ATP inhibit?

A

ATP-sensitive K+ channel Katp

40
Q

During insulin secretion: what depolarises the cell membrane?

A

Inhibition of Katp

41
Q

During insulin secretion: what does depolarisation of cell membrane result in?

A

Opening of voltage-gated Calcium channels

42
Q

During insulin secretion: what does an increase in internal calcium concentration lead to?

A

Fusion of secretory vesicles with the cell membrane and release of insulin

43
Q

How is the release of insulin described?

A

Biphasic

44
Q

Name the two Katp channel proteins?

A

Kir6.1 - inward rectifier subunit, pore subunit

SUR1 - sulphonylurea receptor, regulatory subunit

45
Q

What structure are Katp channels?

A

Octomeric

46
Q

What class of drugs directly inhibits Katp?

A

Sulphonylurea - tolbutamide or glibenclamide

47
Q

What drug stimulates Katp?

A

Diazoxide - which inhibits insulin secretion

48
Q

What do HNF transcription factors play a key role in?

A

Pancreas foetal development and neogenesis and regulate beta cell differentiation and function

49
Q

When can sulphonylurea be used instead of insulin?

A

When there has been robust genetic screening to differentiate MODY from type I diabetes

50
Q

What type of diabetes involves a loss of insulin secreting beta cells?

A

Type I

51
Q

What type of diabetes involves defective glucose sensing in the pancreas and/or loss of insulin secretion?

A

MODY

52
Q

What type of diabetes is initially hyperglycemoa with hyperinsulinemia so the primary problem is reduced insulin sensitivity in tissues?

A

Type II diabetes

53
Q

What family of receptors does insulin receptor belong to?

A

Receptor tyrosine kinases

54
Q

Is protein phosphorylation reversible?

A

Yes

55
Q

What do protein kinases promote?

A

Protein phosphorylation

56
Q

Name the three amino acids that protein phosphorylation occurs on? (any hydroxyl group)

A

Serine
Threonine
Tyrosine

57
Q

What is introduced onto proteins when they get phosphorylated~?

A

A large negative charge

58
Q

Name a dimeric tyrosine kinase?

A

Insulin receptor

59
Q

What is insulin receptor composed of?

A

2 Extracellular alpha subunits and two transmembrane beta subunits linked by disulfide bonds

60
Q

What binds to alpha subunit in insulin receptor?

A

Hormone-binding (insulin) domains

61
Q

What binds to beta subunits in the insulin receptor?

A

ATP-binding and tyrosine kinase domains

62
Q

How does the insulin receptor work?

A

Binding of insulin to alpha subunits causes beta subunits to phosphorylate themselves, thus activating the catalytic activity of the receptor

63
Q

What two pathways does IRS activate once the insulin receptor substrates are phosphorylated?

A
  1. Ras/MAP kinase pathway and gene expression

2. PI3K, PKB, and glycogen synthesis

64
Q

During insulin signalling simplified - what does PKB stimulate?

A

GLUT 4

65
Q

What three things does the biological effect of insulin stimulate?

A
  1. DNA synthesis
  2. Protein synthesis
  3. Glycogen synthesis in liver and muscle
66
Q

What two things does the biological effect of insulin uptake?

A
  1. Amino acid uptake in muscle

2. Glucose uptake in muscle and adipose tissue

67
Q

What are lipolysis and gluconeogenesis in the liver a biological effect of?

A

Insulin

68
Q

Severe insulin resistance and diabetes can be due to a mutation in what?

A

AKT2

69
Q

What disease is a rare autosomal recessive genetic trait, involves mutations in the gene for the insulin receptor, severe insulin resistance and is caused by defects in insulin binding orr insulin receptor signalling?

A

Leprechaunism or Donohue syndrome

70
Q

Give three developmental abnormalities of leprechaunism or donohue syndrome?

A
  1. Elfin facial appearance
  2. Growth retardation
  3. Absence of subcutaneous fat, decreased muscle mass
71
Q

What is the rare autosomal recessive genetic trait that involves severe insulin resistance, hyperglycemia and compensatory hyperinsulinemia, developmental abnormalities and acanthosis nigricans?

A

Rabson Mendenhall syndrome

72
Q

Where are ketone bodies formed?

A

In liver mitochondria - derived from acetyl-CoA fro, beta-oxidation

73
Q

What does ketone body formation depend on?

A

Oxaloacetate

74
Q

What is oxaloacetate consumed for?

A

Gluconeogenesis

75
Q

What type of diabetes is ketoacidosis most associated with?

A

Type I

JL Endocrinology (12 decks)

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