Regulation of glucose Flashcards
what are the 2 types of glucose transport?
passive and active
which passive glucose transporter is found on the basolateral membrane of ileum?
GLUT2
which passive glucose transporter is responsive to insulin?
GLUT4
which passive insulin transporter has a high affinity for glucose?
GLUT4
which sodium glucose symporter is found on the apical surface of the ileum?
SGLT1
which sodium symporter has a high affinity for glucose?
SGLT1
which organ produces insulin and glucagon?
pancreas
where are the b cells located in islets of langerhans and which hormone do they produce?
core (more central)
what do delta cells in the islets of langerhan produce?
SST
which hormone do a cells produce?
glucagon
how does glucose enter pancreatic b cells?
passively via GLUT2 transporters
why does Ca enter the B cells in response to the entry of glucose?
glucose –> glycolysis 00> ATP –> inhibits exit of K –> depolarisation –> Ca entry via voltage gated ion channels
what are the other modulators of insulin secretion?
CCK and Ach
how is insulin secreted?
exocytosis via vesicles
what happens to insulin in golgi bodies?
disulphide bridges formed between chains that fold the hormone
what happens to insulin in golgi and secretory granules?
cleaved into A+B chain and C peptide
what clinical role does c peptide have?
helps to monitor endogenous insulin levels (clinical marker)
in what form is insulin produced?
preprohormone –> cleaved –> prohormone –> golgi bodies
what are the inhibitors of insulin release and how do they work?
SST, sympathetic nervous system via Gi
Which part of the ANS drives insulin secretion?
parasympathetic nervous system
what type of receptor is the insulin receptor?
tyrosine kinase receptor
which AA is the insulin binding domain rich in?
cysteine
what happens in the tyrosine kinase domain of insulin receptors?
neighbouring domains phosphorylate each other and neraby proteins by adding phosphate to tyrosine AA of proteins
what are the 2 main pathways of insulin receptor signalling?
P13K and PKB
MAPK
what does the MAPK pathway do?
phosphorylates transcription factors –> modifies gene expression –> growth/ mitogenic pathways
what do P13K and PKD do?
GLUT4 insertion into membranes by phosphorylating proteins
does oral or IV glucose cause a greater response in insulin?
oral
is the release of insulin biphasic or monophasic?
biphasic
what form is glucagon released in?
proglucagon
what effect does glucose have on glucagon release?
inhibits
what stimulates glucagon release?
AAs
what is GLP1 and where is it secreted?
L cells in small intestine
incretin like glucagon –> stimulates insulin release
which metabolic processes does insulin stimulate in the liver?
glycolysis, lipogenesis, protein and lipid synthesis
which metabolic processes does insulin inhibit in the liver?
gluconeogenesis, ketone body formation
do liver hepatocytes express GLUT4?
no
what happens when there is low insulin?
gluconeogenesis, glycogenolysis
which metabolic pathways are stimulated in muscle cells by insulin?
glycogen synthesis, triglyceride synthesis, protein synthesis
how does glucose enter muscle and fat cells in response to insulin?
GLUT4
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
what is induced in exercise via adrenaline?
GLUT4 insertion
what does somatostatin inhibit?
insulin and glucagon release
where does glucagon mainly act?
liver
what sort of receptor is the glucagon receptor?
GPCR attached to Gs –> PKA –> phosphorylates key enzymes
what does glucagon stimulate in liver cells?
gluconeogenesis, glycogenolysis, fatty acid uptake
why does the shift in metabolism occur in muscle cells and adipocytes?
drop in insulin
why would glycogen be at very high levels?
pathological reason eg ketoacidosis, sepsis
what do very high levels of glycogen stimulate in adipocytes and muscle cells?
lipolysis in adipocytes
proteolysis in muscle cells
where is most glucagon metabolised?
liver
what is he cori cycle?
lactate produced in anaerobic respiration in the muscle used in gluconeogenesis in the liver to produce glucose
what effect does adrenaline have during exercise?
liver –> enhance glucose production
muscle –> glucogen breakdown and fatty acid breakdown
adipocytes –> fatty acids released into blood
which 3 hormones work together to control growth?
thyroid hormone, growth hormone, insulin
what are the acute effects of glucocorticoids?
diabetogenic effects (antagonise the effects of insulin)
how do glucocorticoids affect growth in the long term?
antagonise growth
what happens with an excess of GH in children?
gigantism
what happens with an XS GH in adults?
acromegaly
what happens with a deficiency of GH in children?
dwarfism
what happens with a deficiency of GH in adults?
no obvious disease but more adipose tissue, less muscle bulk, replacement increase vigour
What part of the body integrates signals for growth?
hypothalamus
where is GH released from?
anterior pituitary
what increases GH release from the anterior pituitary?
GHRH
what increases GRH release from the hypothalamus?
amino acids, low glucose, stress, exercise, sleep, TRH, ghrelin
what inhibits GH release?
Somatostatin
by what mechanism does GHRH increase GH secretion?
coupled to Gs which increases cAMP
describe the secretion of GH
pulsatile, more during the night
what are the acute effects of GH release?
diabetogenic, enhancing gluconeogenesis
how does GH bring about acute reponses?
tyrosine kinase associated receptor causes protein phosphorylation
what is the benefit of the diabetogenic effects of GH?
more glucose available for the brain
what mediates the long term effects of GH?
Insulin-like growth factor 1 (somatomedin) released from many tissues in response to GH
How do IGFs (somatomedin) increase protein synthesis?
cross reactivity with insulin increases growth
how does insulin effect growth in utero?
enhances growth (growth stimulus as suggests plenty of food)
how do sex steroids effect growth?
increase growth but premature puberty
is glucocorticoid a type of steroid?
yes
what is the thyroid gland anchored to?
thyroid cartilage
What do C cells of the thyroid hormone release?
calcitonin
what stimulates the release of thyroid hormones?
TSH (thyroid stimulating hormone) released from the anterior pituitary)
what does the parathyroid gland secrete?
parathyroid hormones
what are thyroid hormones essential for?
essential for normal growth and development
what does TH signal there is enough of?
energy
what are the effects of TH?
increases metabolic rate, heat production
How are TH carried in the blood?
bound to proteins predominantly thyroid binding globulin and transthyretin
Which form of TH is more active?
T3
what does TSH stimulate?
nearly all processes in thyroid hormone production
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
which enzyme is involved in adding iodine to thyroglobulin?
iodinase
what is iodine added on to?
2 tyr AAs on thyroglobulin
what happens after iodine has been added to thyroglobulin?
endocytosis and cleaved
Which 3 types of TH are produced?
T3 T4 rT3
what happens to T4?
deiodinated into T3
which 2 enzymes are involved in deiodinating T4?
type 1 and type 2
where is type 1 enzyme found?
liver kidneys thyroid
what is the type 1 enzyme inhibited by?
stress and caloric restriction
where is type II found?
pituitary CNS placenta
what initiates gene transcription?
nuclear receptors
what are the acute effects of TH?
wasting energy, heat production, increasing basal metabolic rate, mitochondrial decoupling
What does TH stimulate in the liver?
gluconeogeneis and glycogenolysis
How do THs affect lipid metabolism?
lipogenesis and lipolysis (free glycerol available for gluconeogenesis)
how do THs affect protein metabolism?
proteolysis and synthesis, net muscle wasting (increase AAs for gluconeogenesis)
how do THs affect B receptor?
increase B receptor expression which increases sensitivity to SNS
what is the chronic effect of TH and what is it crucial for?
brain development and growth crucial in infancy
what does infant TH deficiency lead to?
cretinism and dwarfism
what does TH deficiency in later childhood lead to?
stunted growth
What happens to the thyroid gland if TH levels are very low?
goitre because high levels of TSH
what are the symptoms of hypothyroidism?
weight gain, cold, bradycardia, tiredness, constipation, hair loss, decreased sweating
why might primary thyroid failure occur?
autoimmune or drug induced
how is hypothyroidism diagnosed and what is the treatment?
static tests –> low TH and high TSH (if primary)
T4 replacement
What are the symptoms of hyperthyroidism?
sweating, overeating but weight loss, taccycardia, tremor
what are the main causes of hyperthyroidism?
Graves disease = 80% (autoimmune) toxic nodule = 15% thyroiditis = 1%
what are the clinical signs of grave’s disease?
eye swelling and eye ball protrusion, muscle paralysis
what would be found on examination of someone with hyperthyroidism?
sweating, lid lag, tender thyroid, big goitre, sweaty palms, hand tremor
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
what is the main glucocorticoid?
cortisol
what is the role of the hypothalamus in glucocorticoid release?
integrates stress factors and diurnal rhythm
what does corticotrophin releasing hormone stimulate?
anterior pituitary to release ACRH adrenocorticotrophin releasing hormone
where is cortisol produced?
adrenal glands
which disease results from adrenocorticoid deficiency?
Addison’s disease
what do iatrogenic steroids do?
strong negative feedback inhibiting production of ACTH so adrenal atrophy
what are the acute effects of glucocorticoids?
diabetogenic, inhibit insulin responses, increase lipolysis, glucose targetted to brain, gluconeogenesis and glycogenolysis
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
what happens with excess glucocorticoids?
cushings disease
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
