Regulation of glucose Flashcards
1
Q
what are the 2 types of glucose transport?
A
passive and active
2
Q
which passive glucose transporter is found on the basolateral membrane of ileum?
A
GLUT2
3
Q
which passive glucose transporter is responsive to insulin?
A
GLUT4
4
Q
which passive insulin transporter has a high affinity for glucose?
A
GLUT4
5
Q
which sodium glucose symporter is found on the apical surface of the ileum?
A
SGLT1
6
Q
which sodium symporter has a high affinity for glucose?
A
SGLT1
7
Q
which organ produces insulin and glucagon?
A
pancreas
8
Q
where are the b cells located in islets of langerhans and which hormone do they produce?
A
core (more central)
9
Q
what do delta cells in the islets of langerhan produce?
A
SST
10
Q
which hormone do a cells produce?
A
glucagon
11
Q
how does glucose enter pancreatic b cells?
A
passively via GLUT2 transporters
12
Q
why does Ca enter the B cells in response to the entry of glucose?
A
glucose –> glycolysis 00> ATP –> inhibits exit of K –> depolarisation –> Ca entry via voltage gated ion channels
13
Q
what are the other modulators of insulin secretion?
A
CCK and Ach
14
Q
how is insulin secreted?
A
exocytosis via vesicles
15
Q
what happens to insulin in golgi bodies?
A
disulphide bridges formed between chains that fold the hormone
16
Q
what happens to insulin in golgi and secretory granules?
A
cleaved into A+B chain and C peptide
17
Q
what clinical role does c peptide have?
A
helps to monitor endogenous insulin levels (clinical marker)
18
Q
in what form is insulin produced?
A
preprohormone –> cleaved –> prohormone –> golgi bodies
19
Q
what are the inhibitors of insulin release and how do they work?
A
SST, sympathetic nervous system via Gi
20
Q
Which part of the ANS drives insulin secretion?
A
parasympathetic nervous system
21
Q
what type of receptor is the insulin receptor?
A
tyrosine kinase receptor
22
Q
which AA is the insulin binding domain rich in?
A
cysteine
23
Q
what happens in the tyrosine kinase domain of insulin receptors?
A
neighbouring domains phosphorylate each other and neraby proteins by adding phosphate to tyrosine AA of proteins
24
Q
what are the 2 main pathways of insulin receptor signalling?
A
P13K and PKB
MAPK
25
what does the MAPK pathway do?
phosphorylates transcription factors --> modifies gene expression --> growth/ mitogenic pathways
26
what do P13K and PKD do?
GLUT4 insertion into membranes by phosphorylating proteins
27
does oral or IV glucose cause a greater response in insulin?
oral
28
is the release of insulin biphasic or monophasic?
biphasic
29
what form is glucagon released in?
proglucagon
30
what effect does glucose have on glucagon release?
inhibits
31
what stimulates glucagon release?
AAs
32
what is GLP1 and where is it secreted?
L cells in small intestine
| incretin like glucagon --> stimulates insulin release
33
which metabolic processes does insulin stimulate in the liver?
glycolysis, lipogenesis, protein and lipid synthesis
34
which metabolic processes does insulin inhibit in the liver?
gluconeogenesis, ketone body formation
35
do liver hepatocytes express GLUT4?
no
36
what happens when there is low insulin?
gluconeogenesis, glycogenolysis
37
which metabolic pathways are stimulated in muscle cells by insulin?
glycogen synthesis, triglyceride synthesis, protein synthesis
38
how does glucose enter muscle and fat cells in response to insulin?
GLUT4
39
which metabolic pathways does insulin stimulate in adipocytes?
triglyceride synthesis
free fatty acids exported
lipogenesis into lipid droplets
LPL extracts free fatty acids from VLDLs
40
what is induced in exercise via adrenaline?
GLUT4 insertion
41
what does somatostatin inhibit?
insulin and glucagon release
42
where does glucagon mainly act?
liver
43
what sort of receptor is the glucagon receptor?
GPCR attached to Gs --> PKA --> phosphorylates key enzymes
44
what does glucagon stimulate in liver cells?
gluconeogenesis, glycogenolysis, fatty acid uptake
45
why does the shift in metabolism occur in muscle cells and adipocytes?
drop in insulin
46
why would glycogen be at very high levels?
pathological reason eg ketoacidosis, sepsis
47
what do very high levels of glycogen stimulate in adipocytes and muscle cells?
lipolysis in adipocytes
| proteolysis in muscle cells
48
where is most glucagon metabolised?
liver
49
what is he cori cycle?
lactate produced in anaerobic respiration in the muscle used in gluconeogenesis in the liver to produce glucose
50
what effect does adrenaline have during exercise?
liver --> enhance glucose production
muscle --> glucogen breakdown and fatty acid breakdown
adipocytes --> fatty acids released into blood
51
which 3 hormones work together to control growth?
thyroid hormone, growth hormone, insulin
52
what are the acute effects of glucocorticoids?
diabetogenic effects (antagonise the effects of insulin)
53
how do glucocorticoids affect growth in the long term?
antagonise growth
54
what happens with an excess of GH in children?
gigantism
55
what happens with an XS GH in adults?
acromegaly
56
what happens with a deficiency of GH in children?
dwarfism
57
what happens with a deficiency of GH in adults?
no obvious disease but more adipose tissue, less muscle bulk, replacement increase vigour
58
What part of the body integrates signals for growth?
hypothalamus
59
where is GH released from?
anterior pituitary
60
what increases GH release from the anterior pituitary?
GHRH
61
what increases GRH release from the hypothalamus?
amino acids, low glucose, stress, exercise, sleep, TRH, ghrelin
62
what inhibits GH release?
Somatostatin
63
by what mechanism does GHRH increase GH secretion?
coupled to Gs which increases cAMP
64
describe the secretion of GH
pulsatile, more during the night
65
what are the acute effects of GH release?
diabetogenic, enhancing gluconeogenesis
66
how does GH bring about acute reponses?
tyrosine kinase associated receptor causes protein phosphorylation
67
what is the benefit of the diabetogenic effects of GH?
more glucose available for the brain
68
what mediates the long term effects of GH?
Insulin-like growth factor 1 (somatomedin) released from many tissues in response to GH
69
How do IGFs (somatomedin) increase protein synthesis?
cross reactivity with insulin increases growth
70
how does insulin effect growth in utero?
enhances growth (growth stimulus as suggests plenty of food)
71
how do sex steroids effect growth?
increase growth but premature puberty
72
is glucocorticoid a type of steroid?
yes
73
what is the thyroid gland anchored to?
thyroid cartilage
74
What do C cells of the thyroid hormone release?
calcitonin
75
what stimulates the release of thyroid hormones?
TSH (thyroid stimulating hormone) released from the anterior pituitary)
76
what does the parathyroid gland secrete?
parathyroid hormones
77
what are thyroid hormones essential for?
essential for normal growth and development
78
what does TH signal there is enough of?
energy
79
what are the effects of TH?
increases metabolic rate, heat production
80
How are TH carried in the blood?
bound to proteins predominantly thyroid binding globulin and transthyretin
81
Which form of TH is more active?
T3
82
what does TSH stimulate?
nearly all processes in thyroid hormone production
83
what is thyroglobulin and where is it found in the thyroid gland?
is is a long AA chain with tyr sticking off the end found in the lumen
84
which enzyme is involved in adding iodine to thyroglobulin?
iodinase
85
what is iodine added on to?
2 tyr AAs on thyroglobulin
86
what happens after iodine has been added to thyroglobulin?
endocytosis and cleaved
87
Which 3 types of TH are produced?
T3 T4 rT3
88
what happens to T4?
deiodinated into T3
89
which 2 enzymes are involved in deiodinating T4?
type 1 and type 2
90
where is type 1 enzyme found?
liver kidneys thyroid
91
what is the type 1 enzyme inhibited by?
stress and caloric restriction
92
where is type II found?
pituitary CNS placenta
93
what initiates gene transcription?
nuclear receptors
94
what are the acute effects of TH?
wasting energy, heat production, increasing basal metabolic rate, mitochondrial decoupling
95
What does TH stimulate in the liver?
gluconeogeneis and glycogenolysis
96
How do THs affect lipid metabolism?
lipogenesis and lipolysis (free glycerol available for gluconeogenesis)
97
how do THs affect protein metabolism?
proteolysis and synthesis, net muscle wasting (increase AAs for gluconeogenesis)
98
how do THs affect B receptor?
increase B receptor expression which increases sensitivity to SNS
99
what is the chronic effect of TH and what is it crucial for?
brain development and growth crucial in infancy
100
what does infant TH deficiency lead to?
cretinism and dwarfism
101
what does TH deficiency in later childhood lead to?
stunted growth
102
What happens to the thyroid gland if TH levels are very low?
goitre because high levels of TSH
103
what are the symptoms of hypothyroidism?
weight gain, cold, bradycardia, tiredness, constipation, hair loss, decreased sweating
104
why might primary thyroid failure occur?
autoimmune or drug induced
105
how is hypothyroidism diagnosed and what is the treatment?
static tests --> low TH and high TSH (if primary)
| T4 replacement
106
What are the symptoms of hyperthyroidism?
sweating, overeating but weight loss, taccycardia, tremor
107
what are the main causes of hyperthyroidism?
Graves disease = 80% (autoimmune) toxic nodule = 15% thyroiditis = 1%
108
what are the clinical signs of grave's disease?
eye swelling and eye ball protrusion, muscle paralysis
109
what would be found on examination of someone with hyperthyroidism?
sweating, lid lag, tender thyroid, big goitre, sweaty palms, hand tremor
110
what are the treatment options for hyperthyroidism?
anti-thyroid drug and supplement 6-18 months 50% --> remission block and replace T4 levels
radioactive iodine to destroy gland --> NOT FOR EYE PROBLEMS
surgery --> risky not 1st option
111
what is the main glucocorticoid?
cortisol
112
what is the role of the hypothalamus in glucocorticoid release?
integrates stress factors and diurnal rhythm
113
what does corticotrophin releasing hormone stimulate?
anterior pituitary to release ACRH adrenocorticotrophin releasing hormone
114
where is cortisol produced?
adrenal glands
115
which disease results from adrenocorticoid deficiency?
Addison's disease
116
what do iatrogenic steroids do?
strong negative feedback inhibiting production of ACTH so adrenal atrophy
117
what are the acute effects of glucocorticoids?
diabetogenic, inhibit insulin responses, increase lipolysis, glucose targetted to brain, gluconeogenesis and glycogenolysis
118
what are the chronic effects of glucocorticoids?
immunosuppression, decrease in inflammation and decrease in cytokine production, fat redistribution --> central obesity, skin thinning, muscle wasting, osteoporosis
119
what happens with excess glucocorticoids?
cushings disease
120
what are the symptoms of cushings disease?
truncal obesity, growth arrest in children, moonlike face in adults, acne, poor wound healing, thin skin, easy bruising, striae on abdomen
