28. Insulin Counter-Regulatory Hormones Flashcards
What releases glucagon?
Describe the structure of glucagon. How is it synthesised?
What 3 things stimulate glucagon secretion?
Alpha cells of Islets of Langerhans in pancreas, when blood glucose is low
29aa peptide. Synthesised as preproglucagon -> cleaved to proglucagon and can then be cleaved to give glucagon or a number of different products e.g. GLP-1.
Low BG (normal = 80-90mg/100ml), increase in blood AAs (esp alanine and arginine - glucagon promotes rapid converion of AA -> glucose), exercise (exhaustive)
What is the glucagon receptor and how does this differ from the insulin receptor?
How does the glucagon receptor work?
Which molecules are used by the liver to synthesise glucose?
What 2 things stimulate GNG?
GPCR (7 transmembrane domain); insulin receptor = tyrosine kinase receptor that gets phosphorylated.
Glucagon -> GPCR -> activates G protein -> activates adenylate cyclase -> cAMP produced -> activates PKA -> increases glycogenolysis and reduces glycogen and TGL synthesis. Promotes liver GNG (releases glucose to blood for brain) and lypolysis. Opposite to insulin!
AA, glycerol, and lactate (Cori cycle)
Lack of insulin and presence of glucagon.
What effect does glucagon have in the liver?
What effect does glucagon have on lipids?
Increaes GNG and inhibits glycolysis. Increased AA uptake by liver cells. Inhibition of PFK-1 via modulation of fructose-2,6-bisphosphate, inhibition of pyruvate kinase (both mediated by PKA) (2 key glycolysis steps inhibited!)
Activates lypolysis via HSL (previously inhibited by insulin) -> glycerol (to make glucose -> send to brain) and FA -> beta oxidation -> Acetyl CoA (to produce energy for other tissues). NB: glucagon activates carnitine shuttle (CPT-1)that insulin inhibited, so FA can enter mitochondria and be used to produce ATP
What mechanisms does the liver use to prevent protein loss/muslce wasting?
How is glucagon regulated?
Use Glyerol insead of AAs. FA can be used in most tissues to generate ATP via beta oxidation. Beta oxidation requires certain amount of oxaloacetate for TCA, if imbalance -> Acetyl CoA accumulates -> converted to ketone bodies (ketogenesis) e.g acetoacetate and beta-hydroxybutyrate (KB also synthesised during fasting/after prolonged exercise) BRAIN can use KB!
Secretion inhibited by insulin and somatostatin. Insulin regulates cAMP levels via phosphodiesterase (cleaves cAMP so PKA inactivated); thus insulin stops signalling AND secretion of glucagon.
What are adrenocortical (counter-regulatory) hormones and where are they produced?
Glucocorticoids (longer-acting)produced by adrenal cortex - e.g. cortisol. Catecholamines (shorter-acting), monoamines synthesised from phenylalanine and tyrosine, produced by adrenal medulla - e.g. adrenaline and noradrenaline. Help control BG.
What causes catecholamine release?
What are the metabolic actions of epinephrine (adrenaline)?
What is cotisol and how is it regulated?
What causes its release?
Released in response to stress and hypoglycaemia.
Inhibits insulin and increases glucagon secretion, stimulates glycogenolysis. Increases lypolysis in adipose tissues. Leads to increased BG and FA levels. (Works like glucagon but diff receptor - end point = cAMP activation -> PKA activation so can potentiate activation of glucagon)
Steroid hormone. Adrenal cortex cells have LDL receptors = take up cholestrol to make steroid hormones. Self-regulated: once a certain amount is secreted = stops its further secretion.
Released in response to ACTH (adenocorticotropic hormone) from the pituitary with a negative feedback loop.
What are the metabolic actions of cortisol?
How does it’s intracellular activities differ from adrenaline?
What other functions does cortisol have?
Enhances GNG, inhibits glucose uptake and utilisation, stimulates muscle proteolysis and adipose-tissue lipolysis. Leads to rapid mobilisation of AAs and FAs from cellular stores. (NB: doesn’t usually mobilise basic functional proteins such as muscle contractile proteins and neuron proteins).
Rather than activating PKA, it binds nuclear receptor, enters nucleus and induces gene transcription. Hence longer-acting than catecholamines.
Important in resisting stress (helps maintain BP) and supressing inflammation.
What are the metabolic actions of growth hormones?
Are thyroid hormones counter-regulatory?
What are thyroid hormones?
How are they regulated?
Increases lipolysis (via HSL), reuces glucose uptake and lipogenesis, increases VLDL secretion from liver, increases beta oxidation etc. direct (receptor) and indirect (e.g induces IGF-1 sysnthesis) effects
No - increases basal metabolism rather than oppose action of another hormone.
Iodinated thyronine: tetraiodothyroine, thyroxine (T4)(most abundant), triiodothyronine (T3)(active, only small amount present). TSH -> releases T4 and T3 -> activate nuclear receptors and transcription of a large number of genes.
Controlling conversion of T4 into T3 in target tissues (T3 about 4x more potent than T4). Self regulated - if T4 and T3 conc too high = stops own release.
What are the metabolic actions of thyroid hormones?
What are incretins?
Increase number and activity of mitochondria, stimulate carbohydrate metabolism (glucose uptake, insulin secretion, GNG and glycolysis enhanced), stimulates fat metabolism (lipid mobilied rapidly, increase FA plasma conc). Leads to increased basal metabolic rate.
Group of GI hormones. The most studied: GLP-1 (glucagon-like peptid) and GIP (gastric inhibitory peptide).
Name the kind of cell that produces, and the function of:
a) GIP
b) GLP-1
How is GLP-1 synthesised?
a) K-cell (in proximal intestine), enhances insulin secretion
b) L-cell (in distal intestine and colon), enhances insulin and inhibits glucagon secretion, increase beta cell proliferation/differentiation, increases intracellular Ca2+; inhibits food intake = promotes satiety, secretion and motility
From same precursor as glucagon - cleavage of proglucagon produces it.
Good for treating T2 glucose!
