Insulin Flashcards
Outline the structure of insulin
- Made up of two polypeptide chains joined by 2 disulfide bridges
- 1 internal disulfide bridge on the α chain
Outline the formation of mature insulin
- Preproinsulin produced in RER
- Signal sequence is cleaved in the golgi to produce proinsulin
- Prosinsulin cleaves off the C peptide by proteases to produce mature insulin
Where is insulin secreted from?
Insulin is secreted from β cells in the pancreas
Outline secretion of insulin
- Biphasic
- First a release of preformed insulin
- Synthesis and release of new insulin
What hormone can inhibit insulin secretion?
Adrenaline
What factors stimulate insulin secretion?
- Amino acids
- Fatty acids
Through what transporter does glucose enter β cells?
GLUT2
What is the advantage of the GLUT2 transporter having a low affinity for glucose?
So β cells don’t take up as much glucose when [glucose] is low
How many subunits is the insulin receptor made up of?
4
What is stimulated when insulin binds to the insulin receptor?
Intrinsic tyrosine kinase activity of β subunits
What molecule is an important mediator in insulin signalling?
PIP3
What reverses phosphorylation of PIP3?
PTEN
What is the other role of PTEN?
An important tumour receptor
Where are GLUT4 transporters found?
Specifically in muscle and adipose tissue
How does insulin stimuate glucose uptake in muscle and adipose tissue?
Insulin stimulates movement of vesicles to plasma membrane and delivers GLUT4 transporters to the cell surface so glucose can be moved into the cell
What are the 3 ways of diagnosis of diabetes?
- Oral glucose tolerance test
- Measurement of Plasma Insulin Levels
- Urine analysis
What is the renal threshold?
The [blood glucose] above which glucose can be detected in the urine
How is an oral glucose tolerance test completed?
- Patient is given a drink contaning a known high [glucose]
- Blood glucose is measured ar regular intervals
How are plasma insulin levels tested?
- Competition radioimmunoassays or
- ELISA
Whys is measurement of plasma insulin levels useful?
What is the effect of decreased insulin/glucagon ratio on triglyceride metabolism?
- Increased lipolysis
- Increased fatty acid oxidation
- Increased ketone body formation
How can diabetes be monitored?
- Glucose meter
- Measurement of glycosylated Hb
What is measurement of glycosylated Hb also a measurement of?
Hyperglycaemia
What are the effects of a decreased insulin/glucagon ratio on carbohydrate metabolism?
- decreased gluose uptake by muscle and adipose
- Increased glycogen breakdown
- Increased gluconeogenesis
