LECTURE 9 (Insulin & Glucagon) Flashcards
Which 2 parts does the Pancreas consist of?
Exocrine & Endocrine
Describe the Endocrine part of the pancreas
- Secretes hormones
- Made up of “Islets of Langerhans”
- Include Beta cells, Alpha cells and Delta cells
What are the different cell types in the endocrine part of the pancreas?
- Beta cells = secrete insulin (most abundant) & is centrally located
- Alpha cells = secrete glucagon
- Delta cells = secrete somatostatin
What differentiates insulin from glucose?
Unlike glucose, insulin does not cross the placenta
What are the properties of Insulin?
- Protein hormone
- Insulin + C-peptide are increased insulinoma, whereas exogenous insulin lacks C-peptide
- Insulin structure: alpha chain, beta chain, disulphide bridges & C-peptide
What is C-peptide?
“connecting” peptide which has a long half-life and is an indicator of INSULIN PRODUCTION
Describe how insulin in formed
1) Synthesised as “PREPROINSULIN” made by ribosomes of the RER and is then cleaved into “PROINSULIN”
2) Proinsulin is transported to the Golgi apparatus and packaged into secretory granules
3) Proinsulin is cleaved -> exocytosis of INSULIN + C-PEPTIDE equally
Describe Insulin secretion by pancreatic B cells
Glucose enters B cells -> Increased ATP generated from glucose metabolism closes K+ channels (target of SULFONYLUREAS) and depolarises B cell membrane -> Voltage-gated Ca2+ channels open -> Ca2+ influx and stimulation of insulin exocytosis
[more glucose -> more insulin release]
What is insulin also release in response to apart from glucose?
Amino acids
[especially when glucose + amino acids]
Production of insulin is inhibited by ______________
Epinephrine
What increases and decreases insulin release?
- Beta-2-receptors = increase insulin release
- Alpha-2-receptors = decrease insulin release
[alpha effect is the dominant effect in the pancreas]
What is the result of the Fight or flight response?
Increased plasma glucose
Explanation: If you’re feeling stressed, your body releases stress hormones like cortisol and adrenaline. This should give you an energy boost for a ‘fight or flight’ response. But the hormones actually make it harder for insulin to work properly, known as insulin resistance -> decrease use of glucose for insulin release -> increased plasma glucose
Describe GLUT 1
Insulin-dependent
FOUND IN:
- Blood
- Blood-brain barrier
- Heart (lesser extent)
Describe GLUT 2
- Insulin-dependent
- High Km
- Low affinity
FOUND IN:
- Liver
- Pancreas
- Small intestine
Describe GLUT 3
- Insulin-dependent
- Low Km
- High affinity
FOUND IN:
- Brain
- Neurons
- Sperm
Describe GLUT 4
Insulin-dependent
FOUND IN:
- Skeletal muscle
- Adipose tissue
- Heart
What is the GLUT-2 Transporter?
- Bidirectional glucose transporter
- Found in the liver, kidney, intestine and beta cells of pancreas
- Liver & Kidney -> used for gluconeogenesis
- Beta cells in pancreas -> glucose in/out based on plasma levels (glucose pumped out when low levels and insulin release falls)
What is the GLUT-4 Transporter?
- Stored in vesicles in cells, especially muscle and fat
- Insulin -> PIK3 pathway -> GLUT-4 activation
- Major mechanism for increased glucose uptake
- Depends on insulin (no insulin = no GLUT-4)
What can increase GLUT-4 expression?
Exercise
Describe the pathway for Insulin-dependent glucose uptake
- Insulin receptor is a tyrosine kinase receptor
- Receptor is a tetramer: 2 alpha + 2 beta units joined by disulphide bonds
- Insulin binding -> activation of tyrosine kinase domains -> autophosphorylation -> binds substrates (eg Insulin receptor substrates) which mediates downstream effects (PIK3 PATHWAY & RAS/MAP KINASE PATHWAY)
What are the effects of insulin?
- Glucose uptake (skeletal muscle + adipose tissue)
- Glycogen synthesis -> activates glycogen synthase + inhibits glycogen phosphorylase
- Inhibits gluconeogenesis -> increases fructose 2,6 bisphosphate level
- Fatty acid synthesis -> activates acetyl-CoA carboxylase + inhibits hormone-sensitive lipase
- Protein synthesis -> stimulates the entry of amino acids into cells, important for muscle growth (key side effect of insulin therapy -> weight gain)
- Na+ retention -> increases Na+ resorption in the nephron
- Lowers K+
- Inhibits glucagon release
Why is insulin and glucose used in treatment of hyperkalemia?
Insulin lowers K+ -> enhanced activity of Na/K-ATPase pump in skeletal muscle
What is Glucagon?
- Protein hormone
- Structure: single polypeptide chain
- Synthesised by alpha cells
- Opposes actions of insulin
- Main stimulus for release: low plasma glucose
What are the effects of Glucagon?
- Increases liver glycogen breakdown (raises blood glucose level)
- Increases gluconeogenesis
- Increases amino acid uptake in liver (insulin increases uptake in muscles) -> more carbon skeletons for glucose via gluconeogenesis -> plasma amino acid levels fall
- Activated lipolysis (via hormone-sensitive lipase)
