Endocrine Pancreas and Hormones Flashcards
Where is insulin secreted from
B cells
Where is glucagon secreted from
A cells
Where is somatostatin secreted from
D cells
What is insulin made of
A chain of 21 amino acids
B chain of 30 amino acids
2 disulphide bonds between the chains
And one intrasulfide bone on the A chain
What is insulin initially when made
Proinsulin (contains a C peptide as well which has no biological activity)
How is insulin made
1) insulin gene transcription and translation
2) goes to RER
3) proproinsulin synthesis. These send signal sequences which indicates that it needs further processing
4) Proinsulin transfer to Golgi
5) proinsulin turns to insulin by cleavage of C peptide
6) precipitation of insulin with zinc ions. 2 zinc ions: 6 insulin. This makes insulin stored densely. Insulin is stored like this
7) exocytosis (involves Ca2+ and ATP)
How is proinsulin turned to insulin (name the enzymes and their actions)
1) Proconvertase 1 cleaves at aa 32,33
2) Proconvertase 2 cleaves at 65,66
3) Carboxypeptide H removes 31,32. Also removes 64 and 65 of C peptide
PC1- gives us an insulin molecule with an additional 2 amino acids on the B chain
PC2-gives rise to the C peptide which is free from the insulin molecule at a length of 33aa
CarboxyH- removes extra amino acids on B chain and gives rise to the full insulin molecule
What is the ratio of insulin and C peptide packaged in secretory granule
1:1
when is insulin released and why
1) When blood glucose >5mM
- Increase in glucose metabolism inside islet B cell. Leads to a rise in ATP:ADP ratio. This ratio closes the ATP-sensitive K+ channels. Closure of these channels leads to accumulation of positive K+ inside islet B cells. Increase in positive charge leads to membrane depolarisation which leads to opening of voltage gated Ca2+ channels. Allows extracellular ca2+ to move inside B cell which leads to increased exocytosis and stimulated insulin release
2) Amino acids and fatty acids
What are potentiators of insulin release
Gut hormones (GLP-1, GIP) (incretins)
Glucagon (paracrine communication)
What is the neural control of insulin release
ISlet B cells are stimulated by:
Sympathetic: B-adrenoceptors increase insulin release. A2-adrenoceptors decrease insulin release
Parasympathetic: muscarinic receptors increase insulin release
What does stimulation of sympathetic nervous system predominantly do to insulin secretion
More inhibition than stimulation because there are more a2 adrenoceptors on B cells
What does insulin do in body
Promote growth and development
Promote cellular uptake of K+ via Na+-K+ ATPase pump
Promote uptake and utilisation of glucose in skeletal muscle and adipose
(anabolic). Increases rate of synthesis and storage of energy reserves (glycogen and fats) and of protein
Effects of insulin on muscle
Increased glucose uptake via GLUT4
increased protein synthesis
Decrease protein breakdown
Effects of insulin on adipose tissue
Increased glucose uptake via GLUT4
Increased lipogenesis
Decreased lipolysis
