Principles Flashcards
1
Q
what is meant by endocrine glands?
A
ductless glands that secrete into the bloodstream
2
Q
the anterior pituitary releases what hormone?
A
adrenocorticotropic hormone ACTH
3
Q
what does the release of ACTH cause?
A
adrenal cortex synthesises and releases cortisol
4
Q
specificity of signalling is achieved by what three things?
A
chemically distinct hormones
specific receptors for each hormone
distinct distibution of receptors across target cells
5
Q
list the major endocrine organs
A
hypothalmus
pituitary
thyroid (and parathyroid)
adrenal
pancreas
ovary/testes
pineal and hypothalmus also
6
Q
what are the four chemical natures of hormones?
A
Modified amino acids
Steroids
Peptides
Proteins
7
Q
give examples of modified aminoo acid hormones
A
adrenaline
thyroid hormones
8
Q
give examples of steroid hormones
A
cortisol
progesterone
testosterone
9
Q
give examples of peptide hormones?
A
adrenocorticotropic hormone ATCH
antidiuretic hormone ADH
oxytocin
10
Q
give example of protein hormone
A
insulin
11
Q
what are the three types of chemical signalling
A
autocrine
paracrine
endocrine
12
Q
describe autocrine signalling
A
cell releases signaling molecules that stimulate an effect on the same cell itself
13
Q
describe paracrine signalling
A
cell releases signalling molecules that diffuse over a short distance in the interstitial fluid
14
Q
describe endocrine signalling
A
cell synthesises signalling molecule then releases it into bloodstream
15
Q
which chemical signalling works over ong distance?
A
endocrine signalling
16
Q
how do hormones in endocrine signalling affect organs?
A
integrates organ function with hormones at very low concentration
17
Q
in endocrine signalling hormones bind to what to initiate a biological response?
A
cognate receptors- (specific)
18
Q
what triggers a biological response in endocrine signalling?
A
activated receptor engaging a signal transduction cascade
19
Q
what is the purpose of the signal transduction cascade?
A
amplification of the original signal
20
Q
hormone action is slower/faster than neurotransmitters?
A
slower
(seconds to days)
21
Q
how is hormone action terminated?
A
enzyme mediated metabolic inactivation in the liver, or at sites of action
22
Q
which hormones contribute to the response of the body to short term intense exercise?
A
adrenaline
cortisol
glucagon
23
Q
adrenaline, cortisol and glucagon prevent what?
A
hypoglycaemia
hypokalaemia
24
Q
which hormones are essential for normal growth?
A
growth hormone (GH)
insulin
IGF-1
sex steroids
25
give an example of hormones that have an antagonistic action?
insulin v glucagon
26
how are amines synthesised and stored?
they are **pre-synthesised** and _stored in vesicles_
27
what triggers the release of amines?
Ca2+ dependant exocytosis
28
how are amines transported?
mainly 'free' in the plasma
29
are amines hydrophilic/phobic?
hydro**philic**
30
how are peptides and proteins synthesised and stored?
**pre-synthesised** usually from longer chain and _stored in vesicles_
31
where in the cell are the precursor proteins for peptide hormones synthesised?
ribosomes of the rough ER
32
what triggers the release of proteins and peptides?
Ca2+ dependant exocytosis
33
how are protiens and petides transported?
mainly 'free' in the plasma
34
peptides are hydrophilic/phobic
hydro**philic**
35
how are steroids synthesised and stored?
they are synthesised and secreted **upon demand**
36
what affects the rate of synthesis of steroids?
1) Cellular uptake and availabiloty of cholesterol
2) Rate of conversion of cholesterol to pregnenolone
37
what is the rate limiting step in the synthesis of steroids?
conversion of _cholesterol to pregnenolone_
38
steroids are hyrdrophilic/phobic
hydro**phobic**
39
how are steroids transported?
90%- bound to _plasma proteins_
10%- free
40
which three hormones are relatively insoluble in plasma?
Steroids
thyroxine (T4)
triiodothyronine (T3)
41
what are the three main functions of carrier proteins?
1. inc amount transported in blood
2. provide reservoir of hormone
3. extend half-life of hormone in circulation
42
what are the three **specific** carrier proteins?
cortisol-bindign globulin (CBG)
thyroxine-binding globulin (TBG)
sex steroid-binding globulin (SSBG)
43
what are the two **general** carrier proteins?
**albumin**- binds many steroids and thyroxine
**tranthyretin**- binds thyroxine and some steroids
44
which hormones are souluble in plasma and do not require carrier proteins?
proteins and peptides
45
which molecules act as a buffer and reservoir in the blood?
carrier proteins
46
free and bound hormone are in equilibrium in the blood true/false
**true**- carrier proteins maintain relatively constant conc of free _lipophilic_ hormone in the blood
47
only ____ hormone can cross the capillary wall
**free**
48
free hormones activate receptors where?
target tissues
49
how are surges in hormone secretion controlled?
buffered by binding to carriers
note: free conc doesnt rise abruptly
50
how is free hormone removed from plasma?
elimination
51
what happens when free hormone is removed from the plasma?
replaced by bound hormone dissociating from carrier protein
52
what mechanism controls the synthesis and concentraon of cortisol?
negatiev feedback
53
what is short range negative feedback of cortisol?
cortisol carried back to the pituitary where it supresses release of ACTH
54
what is long range negative feedback control of cortisol?
cortisol carried back to hypothalmus to prevent further synthesis of cortisol
55
what does the hypothalmus release in the cortisol synthesis pathway?
secretes corticotropin releasing hormone
56
what does corticotropin releasing hormone from the hypothalmus act on?
anterior pituitary
57
what does the anterior pituitary secrete in the cortisol synthesis pathway?
adrenocorticotropic hormone
58
what does adrenocorticotropic hormone act on in the cortisol synthesis pathway?
adrenal cortex
59
what structure secretes cortisol
adrenal cortex
60
what is the name given to the fluctuation of cortisol secretion rate over time?
diurnal (circadian) rhythm
61
when is the plasma concentration greatest during hte day?
12.00pm before decreasign until 24.00am and then increasing again
62
how does elimination of cortisol occur?
metabolism by the liver
excretion by the kidneys
63
plasma conc of hormone= ?
rate of secretion- rate of elimination
64
what is the half life of amines e.g adrenaline?
seconds
65
what is the half life of proteisn and peptides?
minutes
66
what is the half life of steroids and thyroid hormones?
hours- days
67
what are the two groups of hormone receptors?
cell surface receptors
intracellular receptors
68
which hormone receptor is hydrophilic and which is lipophilic?
cell surface- ligand is **hydro****philic**
intracellular receptor- ligand is **lipophilic**
69
what are the two kinds of cell surface hormone receptor?
G-protein coupled
Receptor kinases
70
what activates G-protein coupled receptors?
amines
some proteins/peptides
71
what activates receptor kinases?
some proteins/peptides
72
intracellular receptors are what kind of receptors?
nuclear receptors
73
nuclear receptors can be subdivede into what?
class 1
class 2
hybrid class
74
what activates class 1 nuclear receptors?
many steroid hormones
75
what activates class 2 receptors?
mostly by lipids
76
what activates hybrid class nuclear recpetors?
thyroid hormone (T3)
77
where are nuclear receptors found?
in the nucleus or in the cytoplasm
78
which type of hormone receptors are ligand-gated transcription factors?
nuclear receptors
79
steroid hormones are lipophilic and enter cells by _____ across teh plasma membrane
diffusion
80
what do steroid hormones combine with in the cell producing dissociation of inhibitory HSP proteins?
intracellular receptor
81
in nuclear reeptor signalling the receptor steroid complex forms a dimer and binds to what?
hormone response elements in DNA
82
what is the final step in nuclear receptor signalling?
transcription of specific genes is either 'swithced-on' or 'swithced-off' to alter the rate of synthesis of **mediator proteins**
83
what are the cells of pancreatic islets?
beta cells
alpha cells
s cells
PP cells
84
what do islet beta cells secrete?
insulin
85
what do alpha islet cells secrete?
glucagon
86
what do s islet cells secrete?
somatostatin
87
what do PP islet cells secrete?
pancreatic polypepetide
88
glucose homeostasis controls what?
blood sugar concentration
89
what is the normal blood gluocse concentration?
5mmol
90
where is insulin originally formed before being cleaved?
rough ER of B cells as a large chain
91
what is the byproduct of cleavage of insulin
Connecting (C) peptide- no physiological function
92
what is the name given to the insulin preparation given to diabetcis at nightitme to control their blood sugar while they sleep?
glargine
93
how does glucose enter B cells?
enters through **GLUT2** glucose transporter
94
what is the name of the enzyme that phosphorylates glucise once in the B cells?
phosphorylated by **glucokinase**
95
a change in _glucose conc_ leads to dramatic change in _glucokinase activity_ true/false
True
96
increased metabolism of glucose leads to an increase/decrease in intraclellular ATP concentraion
increase
97
how many ATP are produced per glucose in glycolysis?
36ATP
98
ATP inhibits what within the secretion of insulin?
ATP sensitive K+ channel (KATP)
99
what does the inhibition of KATP lead to within the secretion of insulin?
**depolaristion** of the cell membrane
100
in the secretion of insulin depolaristion of he cell membrane results in what?
opeing of voltage gated Ca2+ channels
101
in insulin secretion an increase in internal Ca2+ conc results inthe release of what?
insulin
102
what is the only cell in the body capable of synthesisng and releasign insulin?
B cells
103
when will B cells release insulin?
when blood glucose rises above 5mmol
104
what happens ot the B cells in T1DM
they are mostly lost
105
what happens to the B cells in other types of diabetes than T1DM?
B cells lose the abiloity to sense changes in glucose
106
describe the pattern of release of insulin?
release of insulin is **biphasic**
107
what % of insulin granules are availale for immediate release?
5%
108
what does RRP stand for in insulin secretion?
Readily Releasable Pool
109
what is used in the second phase of insulin release?
reservoir pool
110
in poorly controlled T2DM what happens to insulin secretion?
it weakens and flattens
111
Which drugs mimic the action of ATP to depolarise B cells in T2DM?
sulphonylurea drugs
112
KATP channels consist of which two proteins?
Kir6
SUR1
113
KATP channels exist as an _______ structure?
**octomeric** structure
114
the **sulphonylurea** class of drugs directly inhibits what?
KATP
115
KATP is stimulated by _______ which inhibtis insulin secretion?
diazoxide
116
what is the second line therapy for T2DM
sulphonylurea drugs
117
which type of mutation can lead to **neonatal** diabetes
mutation in the potassium channels of B cells
118
some Kir6 or SUR1 mutations can lead to what?
congenital hyperinsulinism
119
what does MODY stand for?
Maturity-onset diabetes of the young
120
what is the treatment for MODY1 rather than type 1
SUlphonylurea rather than insulin
121
describe the defect in MODY
defective glucose sensing in the pancreas and/or loss of insulin secretion
122
describe the insulin signalling pathway
1. **reception**- signal molecule acts on receptor
2. **transduction**
3. **response**
123
binding of insulin to the alpha subunits causes the beta subunits ot do what?
dimerise and phosphorylatr themselves
124
what activates the catalytic activity of the insulin receptor?
phosphorylation of the beta subunits
125
describe insulin resistance?
reduced ability to respond to physiological insulin levels
126
insuin is the key hormone in preventing what?
hyperglycemia
127
Developmental abnormalities, growth retardation and the absence of subcutaneous fat with decreased muscle mass is seen in which severe insulin resistance syndrome?
donohue syndrome
128
developmentl abnormalities, acanthosis nigricans (hyperpigmentation) and diabetic ketoacidosis is seen in which severe insulin resistance syndrome?
Rabson Mendenhall syndrome
129
what are the symptoms of diabetic ketoacidosis (DKA)?
vomiting
dehydration
inc heart rate
distinctive smell on breath
130
where are ketone bodies formed?
liver mitochondria
131
what are ketone bodies derived from?
acetyl-CoA from the B oxidation of fats
132
ketone bodies are important molecules of energy metabolism for what?
heart muscle
renal cortex
133
what happens to ketone bodies once they have been used for enrgy metabolism?
converted back to acetyl-CoA which then enters the TCA cycle
134
low levels of insulin inhibit _______ preventing ketone body overload
lipolysis
135
in the TCA cycle low levels of which molecule will result in acetyl-CoA being converted to ketones?
oxaloacetate
136
oxaloacetate is consumed for which process?
gluconeogenesis
137
how would you treat DKA?
insulin and rehydration
138
what are the greek meanings for **mellitus** and **insulin**?
mellitus- sweet (urine was sweet smelling due to high sugar content)
insulin- island (islet cells looked liek islands under microscope)
139
which of the insulin hexamer and the insulin monomer is the active form?
insulin hexamer- inactive
## Footnote
**insulin monomer- active**
140
T1DM is not diagnosable before what age?
1 yr- neonatal can be transient
141
