Main hormones regulating blood glucose levels Flashcards
Explain the MoA of insulin secretion from B cells
Glucose enters the β-cells
Glucokinase acts as the glucose sensor
Increased ATP/ADP ratio closes the ATP-sensitive potassium channel leading to depolarisation of the plasma membrane
This opens the voltage-gated calcium channel. The increase of intracellular calcium triggers secretion of insulin-containing granules
Name other signals that can potentiate the insulin other than last slide [6]
- Intracellular catobolsim of amino acids increases cellular ATP / ADP ratio (leucine, arginine)
- Fatty acids
- Glucagon like peptide 1 (GLP-1)
- Glucose-dependent insulinotropic
peptide (GIP) - PNS release of Ach
- CCK
(most require glucose for activation)
Name & explain the roles of insulin in the
a) liver [3]
b) adipocytes [3]
c) skeletal muscles [3]
Skeletal Muscles:
* Glucose uptake in muscles via GLUT 4 translocation
* Glycogen synthesis in muscles (activates glycogen synthase)
* Inhibits protein catabolism
Adipocytes:
* Stimulates lipogenesis (activation of AcetylCoA carboxylase)
* Inhibits lipolysis
* Promotes glucose uptake via GLUT 4 translocation
Liver:
* enhances glucose uptake to increase glycogen synthesis
* increases lipogenesis
* inhibits gluconeogenesis
Which cells release glucagon? [1]
Alpha cells of islet of Langerhans
What is glucagon initially synthesised as? [1]
Proglucagon: converted to glucagon
What is glucagon secretion stimulated by? [3]
What is glucagon secretion inhibited by? [5]
Stimulated:
* Low blood glucose conc
* Increased blood A.A (especially alanine and arginine)
* Exercise
Inhibited:
* Hyperglycaemia
* GLP-1
* Somatostatin
* Insulin
* Zinc
Explain MoA of glucagon working
- Which type of receptor does it bind to?
- Glucagon receptor is a GPCR
- Upon ligand bonding, GTP displaces GDP on the a subunit. A subunit binds to the adenyly cyclase protein to activate
- Causes activation of Adenyly Cyclase pathway
(pathway is a key signalling cascade activated by glucagon). - Causes synthesis of cAMP as a second messenger (v important!) which actiavtes protein kinase A causes phosphorylation of enzymes used for reactions to make glucose
How does insulin switch off glucagon dependent signaliing?
Phosphodiesterase
Glucagon acts mainly on which organ? [1]
Liver
Effect of glucagon on [4]
glycogenlysis
glycogensis
At the liver: gluconeogenesis
glycolysis
Glucagon increases glycogenolysis
Glucagon inhibits glycogenesis
AND
At the liver: Inhibits glycolysis and increases GNG
What is the effect of glucagon on precursors for GNG?
COME BACK
Glucagon increases amino acids, lactate, and glycerol intake by hepatic cells
Which other hormones (in addition to glucagon) regulate glucose levels? [5]
Other counter-regulatory hormones:
* Catecholamines (adrenaline / noradrenalone) produced in adrenal medulla
* Glucocorticoids (cortisol)
* Growth hormone
Other hormones;
* Thyroid hormones
* GLP-1
*
Role of catecholamines (in particular adrenaline) with regards to hypoglycaemia
Fight or flight x
E.g. Adrenaline:
It also acts as an insulin counter-regulatory hormone in response to hypoglycaemia
It signals via a G protein-coupled receptor: produces cAMP and causes activation of PKA
What is the effect of adrenaline with regards to insulin when someone is hypoglycaemic?
Adrenaline: acts as insulin counter-regulatory hormone when hypoglycaemic by producing cAMP and activating PKA in liver and skeletal muscle.
Causes glycogenlysis so that glucose can be released in the blood and used in muscle to produce ATP or lactate
Catecholamines monoamines (Dopamine, norepinephrine, and epinephrine) are synthesised from which two molecules? [2]
Where? [1]
Adrenaline synthesised from Phenylalanine and Tyrosine
At: chromaffin cells of the adrenal medulla
Which glucocorticoid do u need to know? [1]
Which molecule are glucorticoids derived from? [1]
Cortisol
Derived from cholesterol
Which pathway is cortisol regulated through? [1]
When is cortisol released? [1]
What is the overall effect of cortisol being released? [2]
Corticol is regulated via Hypothalamus/Pituitary/Adrenal axis
Cortisol is important to resist stress and inflammation
HOW: maintaining blood pressure and suppressing inflammation
What is cortisol associated with? [1]
Cortisol is important to resist stress and inflammation
What is cortisol associated with? [1]
Cortisol is important to resist stress and inflammation
Effect of cortisol in:
a) the liver [2]
b) the muscle [2]
c) adipocytes [2]
(opposite of insulin; similar to glucagon)
In the liver:
* enhances gluconeogenesis
* inhibits glycogen synthesis
In muscle:
* inhibits glucose uptake/utilisation
* stimulates protein degradation
In adipocytes:
* it stimulates lipolysis
* Rapid mobilisation of glucogenic amino acids and glycerol/fatty acids from cellular stores
Growth hormone acts by activating which two receptors?
GH acts via Growth Hormone receptor [1] and Prolactin receptor [1]
Growth Hormone receptor is what type of specific receptor? [1]
GHR is a type I cytokine receptor that lacks intrinsic kinase activity and requires recruitment of Tyrosine kinases to signal
Growth hormone is stimulated by the release of which hormone? [1]
Growth hormone is inhibited by the release of which hormone? [1]
Growth hormone:
- stimulated by growth hormone-releasing hormone (GHRH)
- inhibited by somatostatin (SSTN)
What are the metabolic effects of growth hormone at:
a) liver [2]
b) sk. muscle
c) adipose tissue
What are the metabolic effects of growth hormone at:
a) adipose tissue:
* reduces lipogenesis
* Increases lipolysis
* Overall effect: reduces body fat mass
b) sk. muscle
* Reduces glucose uptake
* Increases b oxidation
c) liver:
* increases production and uptake of IDL, LDL and HDL