Glucagon and Insulin Flashcards
What is the pancreas divided into ?
An exocrine portion (acinar and duct tissue) and an endocrine portion (islets of Langerhans)
What does the exocrine glands and endocrine glands produce?
Exocrine glands: digestive enzymes, etc
Endocrine glands: hormones
What is the structure of pancreatic islets of Langerhans?
The beta-cells are situated in the centre of the islets with the other cells in the periphery
What stimulates islets of langerhans ?
The islets are highly innervated by the sympathetic and parasympathetic nervous system and have a high blood flow so the cells are ideally placed to sense the nutrient composition of the
blood
What do beta cells and alpha cells secrete ?
- Beta cells secrete insulin
- Alpha cells secrete glucagon
What chain is Glucagon and where is it made in ?
Glucagon is a single chain peptide (29aa) made in the pancreatic α cells
What are both Glucagon and glucagon-like peptides derived from ?
Proglucagon: tissue-specific proteases determine which product is produced by which cells
Besides insulin and glucagon, there are many other other signals that regulate food
intake, including a complex range of peptides secreted from the GI tract such as ?
- Cholecystokinin
- Glucagon-like peptide 1 (GLP-1)
What is Cholecystokinin (CCK)?
This is a family of small peptide hormones secreted by cells of the intestine following a meal. CCK binds to its receptor in nerve cells,
causing increased feelings of satiety via the brain
What is Glucagon-like peptide 1 (GLP-1) ?
This is a 30 amino acid
hormone secreted by the L cells of the intestine. Once bound to its receptor, GLP-1 induces feelings of satiety in the brain and potentiates insulin secretion while inhibiting glucagon secretion
What is low-high blood glucose a major factor in ?
Stimulating/inhibiting glucagon secretion
What also has an affect on secretion of glucagon secretion ?
A range of gut peptides and hormones, notably adrenaline
What is the mechanism of glucagon action via cAMP ?
- Glucagon binds to the glucagon receptor in liver and
adipose tissue (only) - This activates the Gαs G protein, which in turn activates adenylate cyclase
- AC synthesises cAMP
- cAMP activates protein kinase A (PKA)
- PKA phosphorylates on ser/thr residues:
Synthesis: OFF
Breakdown: ON
What pathways does the metabolic effect of glucagon generally inhibit and stimulate?
- Inhibits anabolic pathways (build larger molecules from smaller oner, which requires energy)
- Stimulates catabolic pathways (release energy by breaking down larger molecules)
What does glucagon inhibit ?
Inhibits glycolysis in most tissues
What is the effect of glucagon on cardiac stimulation ?
Increases contractility, little effect on rate
What is the effect of glucagon on insulin ?
To stimulate insulin secretion from the islet beta cells
Why does glucagon not function in the skeletal muscle?
As there are no glucagon receptors
What is the key regulatory enzyme in glycolysis ?
Phosphofructokinase-1
What is the key regulatory enzyme in gluconeogenesis?
Fructose-2,6-bisphosphatase
What is used for glycogen regulation ?
Phosphorylase kinase and glycogen synthase
What is downstream of insulin (so antagonising insulin-induced effects) ?
Protein Phosphatase (PP1)
Explain the steps of Insulin biosynthesis ?
- Insulin mRNA goes to ribosomes where it is processed into preproinsulin (11.5kDa)
- Preproinsulin contains A and B chains and a signal peptide
which allows it to be secreted into the cisternae of the rER. - Preproinsulin moves from ER to Golgi where signal peptide
cleaved off, producing pro-insulin (9kDA): has to fold
precisely due to disulphide bridges - Dipeptide sites between A and B chain cleaved and
connecting C peptide is cut out - This reduces solubility: forms microcrystals with zinc and
packaged into vesicles for secretion
How do you stain immature secretory vesicles ?
Stain with the proinsulin
antibody, but not with the
insulin antibody
How do you stain mature secretory vesicles ?
Stain with insulin antibody,
but not with proinsulin
antibody
What inhibits Insulin release?
- Mannoheptulose
- Respiratory chain inhibitors
Explain glucose regulation of insulin secretion ?
- Glucose (>7mM) enters β cells via GLUT2
- Glucose enters glycolysis, resulting in a rise in ATP
- ATP binds to ATP-gated K+ channels.
- K+ channels close, depolarise the plasma membrane
- Depolarisation triggers opening of voltage-gated Ca2+ channels
- Increased Ca2+ in cytosol triggers release of insulin by exocytosis
Explain the metabolic actions of insulin (via RTK) ?
- Many effects mediated by dephosphorylation of key enzymes by PP1, and increased
breakdown of cAMP by stimulating phosphodiesterase - Generally stimulating anabolic pathways and inhibiting catabolic ones
What is the key role of increasing GLUT4 transporters on muscle and adipose cell
membranes to ?
Increase glucose uptake
What is Glucokinase used for?
- Glucose sensor
- Enables glycolysis
What catalyses the key
conversion of pyruvate to acetyl-CoA ?
Pyruvate dehydrogenase
