Basic Science Flashcards

1
Q

What cells secrete insulin and glucagon?

A
  • insulin: Beta cells

- glucagon: Alpha cells

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2
Q

What so delta and PP cells secrete?

A
  • delta cells: somatostatin

- PP cells: pancreatic polypeptide

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3
Q

What is the simple pathway for the production of insulin?

A
  • made in the RER of pancreatic beta cells as preproinsulin
  • this is cleaved to make insulin
  • C peptide is made in a 1:1 ratio (no known function)
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4
Q

What is the short-acting form of insulin?

A

lispro= most rapid acting and is used in combination with longer acting types

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5
Q

What is the long-acting form of insulin?

A

glargine= released slowly into the blood and the level is maintained during sleep

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6
Q

What is the process of secretion of insulin?

A
  • glucose enters beta cells through GLUT2
  • glucose is phosphorylated by glucokinase
  • increase in glucose metabolism so increase in intracellular ATP from respiration
  • ATP inhibits ATP-sensitive K+ channels
  • this causes depolarisation
  • voltage-gated Ca2+ channels open
  • an increase in Ca2+ causes insulin to be released
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7
Q

What are the features of glucokinase?

A
  • Km is at ideal glucose concentration

- action increased as glucose increases

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8
Q

What is the fasting glucose in diabetics?

A

above 7

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9
Q

What is the pattern of release of insulin from a beta cell?

A

it is biphasic with a reserve pool and a readily releasable pool (RRP)

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10
Q

What is the structure of a Katp channel?

A
  • 4x Kir6
  • 4x SUR1
    this forms an octomeric structure
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11
Q

What are the factors that can cause change in Katp?

A
  • normally, ATP inhibits Katp to cause depolarisation
  • Katp can be inhibited by sulphonylurea
  • Katp can be stimulated by diazoxide
    (overwork Beta cells)
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12
Q

What mutation can lead to neonatal diabetes?

A

Kir6.2 which is part of the Katp channel as there will be more Katp channels and they will be overactive

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13
Q

What is MODY?

A

Maturity-onset diabetes of the young

  • familial disease with beta cell genetic defect
  • associated with transcription factors
  • MODY2 involves glucokinase impairment
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14
Q

What are the definitions of the types of diabetes?

A
  • Type 1= loss of insulin secreting beta cells
  • MODY= defective glucose sensing and/or loss of insulin secretion
  • Type 2= hyperglycaemia with hyperinsulinaemia so there is decreased insulin sensitivity in tissues
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15
Q

What are the processes that insulin promotes?

A

this is an anabolic hormone

  • amino acid uptake in the muscle
  • DNA synthesis
  • protein synthesis
  • growth repossess
  • glucose uptake in muscles and adipose tissue
  • lipogenesis in adipose tissue and liver
  • glycogen synthesis in liver and muscle
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16
Q

What are the processes that insulin inhibits?

A
  • gluconeogenesis in the liver

- lipolysis in the adipose tissues

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17
Q

What is the outline of insulin sensing?

A
  • insulin receptors = receptor tyrosine kinase

- signalling pathways = PI3K and RAS which are regulated by growth factors

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18
Q

What are the features of Leprechaunism?

A
  • association with dwarfism
  • defects in insulin binding or insulin receptor signalling
  • growth problems
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19
Q

What are the main features of DKA?

A
  • increased HR
  • vomiting
  • dehydration
  • smell of ketones on breath
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20
Q

Where are ketone bodies made?

A

liver mitochondria

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21
Q

How are ketone bodies made?

A

when the ration of carbohydrates:fatty acids is changed when there is an increase in FAs the more ketone bodies are made from acetyl-coA

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22
Q

What are ligand-gated ion channels?

A
  • in neurones and muscle cells
  • bound and activated by hormones and neurotransmitters
  • these cause a response in milliseconds
23
Q

What happens to open ligand-gated ion channels?

A

there is a chemical change when the hormone binds so there is structural change

24
Q

What disease occurs when ligand-gated ion channels are distrupted?

A

Myasthenia Gravis- autoimmune condition with loss of ACh receptors

25
What is the process of reaction in a GPCR?
- hormone binds to eg B2 causing a conformational change - G proteins attach - alpha is coupled to GDP so when it binds, GDP is made into GTP - Alpha activates adenylyl cyclase - ATP --> cAMP --> PKA - PKA inhibits MLCK activity - GTP hydrolysis stops the process
26
What actions can adrenaline have at different cells?
- at beta2 = bronchodilator by activation - at alpha2 = relaxes GI tract by inhibition - at alpha1 = vasoconstrictor by activation
27
What does adrenaline do to cause relaxation of the GI tract?
- adenylyl cyclase is already working in alpha2 - Galpha causes this to switch off - betax causes activation of K+ channels so there is inhibition - this causes relaxation of the GI tract
28
How does adrenaline cause vasoconstriction?
- when bound to alpha1 it activates phospholipase C so PIP --> DAG IP3 - this increases the amount of Ca2+ ions so there is vasoconstriction
29
What are the features of receptor tyrosine kinases?
- there a many cellular responses | - these occur in hours
30
What is the process of activation of receptor tyrosine kinases?
- insulin binding causes conformational change - this unites parts of the receptor - autophosphorylation - tyrosine is phosphorylated by ATP molecules - relay proteins attach and activate other proteins
31
What does autocrine mean?
chemicals released from cells bind to receptors on or in the cell releasing them which is usually negative feedback
32
What does paracrine mean?
chemicals released from cells bind to receptors on adjacent cells
33
What does endocrine mean?
chemicals released from secretory cells transported via circulatory system and target cells that are some distance away
34
What are the different intrinsic and extrinsic responses?
- intrinsic= paracrine and autocrine | - extrinsic= nervous system and endocrine
35
What are the main endocrine glands?
- pituitary and hypothalamus - parathyroid - adrenals - pancreas - ovaries - testes - thyroid
36
What are the subtypes of hormones?
- steroids : derived from cholesterol - proteins and peptides : amino acid chains - tyrosine and tryptophan derivatives : amino acid based
37
What do different levels of TSH mean?
- suppressed : hyperthyroid - normal : normal thyroid - raised : hypothyroid
38
What are the major glands of the body?
- thymus - adrenals - pancreas - testes - hypothalamus - pineal - pituitary - ovary - thyroid - parathyroid
39
What is a hormone?
a substance elaborated by one cell to regulate another cell
40
What does the hypothalamus do?
- is controlled by the nervous system - regulates secretion of regulatory hormones - synthesises hormones and transports them - controls secretion of adrenaline and noradrenaline to regulate sympathetic control
41
What are levels of hormone determined by?
- diurnal control dependent on external cues such as light and dark - dependent on rate of elimination from the body
42
What is an example of hormones that have complementary actions?
glucagon and cortisol
43
What are the features of steroid hormones?
- hydrophobic and lipophilic - synthesis rate controls the amount (depends on diurnal expression of enzymes of production) - not stored, only secreted - can pass through bilayer - bind to steroid receptor in cytoplasm which transports it to nucleus
44
What are the features of amine-derived hormones?
- hydrophilic so need receptor to get in - catecholamines can move inside unbound - thyroid amine hormones are bound to carrier proteins - tyrosine is precursor for catecholamines - stored until needed
45
What are the features of peptide and protein hormones?
- usually have a tertiary structure - hydrophilic so are unbound in plasma - synthesised as precursors and stored
46
Which hormones need carrier proteins?
steroid and thyroid
47
What does binding to carrier proteins do to the hormones?
- facilitates hormone transport - increases half-life - provides reservoir for hormone
48
What do monogenic and polygenic mean?
- monogenic is one causative gene | - polygenic is multiple causative genes
49
How are mitochondrial defects passed?
through the paternal line
50
What are the features of Von Hippel Lindau?
this is an autosomal dominant condition which causes vascular tumours
51
What are the features of Neurofibromatosis Type 1?
- axillary freckling - cafe-au-lait patches - neurofibromas - this is a common condition
52
What does plasma osmolality equal?
2(Na+ + K+) + urea + glucose
53
What process generates ketone bodies?
lipolysis leads to ketoacidosis
54
What molecule binds the majority (70%) of thyroid hormone?
thyroxine binding globulin