Normal insulin signalling Flashcards
What does insulin secretion stop?
Gluconeogenesis Glucogenolysis Lipolysis Ketogenesis Proteolysis
What does insulin secretion promote?
Glucose uptake Glycolysis Glycogen synthesis Protein synthesis Uptake of ions (K+, PO43-)
How is insulin produced?
Preproinsulin Loss of signal sequence Proinsulin Loss of C chain Insulin
What happens to the C chain?
Exported with no known physiological effect
Where is insulin processed?
In the endoplasmic reticulum of the beta cell
Has high number of ER
What is basal blood glucose?
5.5mM
Any higher stimulates insulin
How is insulin secreted in response to glucose?
Glucose enters the beta cell Enters glycolysis and Krebs Produces ATP Membrane depolarisation Ca2+ influx Signal to release insulin
How does glucose enter the beta cell?
Via Glut2 transporter
What enzyme first acts on glucose?
Glucokinase phosphorylates glucose to glucose-6-phosphate
What is the effect on ATP production in the beta cell?
ATP has a negative effect on the ATP-sensitive K+ channel
Closes it
Causes depolarisation
How does Ca2+ enter the beta cell?
Via the Ca2+ voltage gated channel
What are the phases of insulin release?
First phase - stored granules released in response to glucose
Second phase - stores depleted and insulin must be synthesised
Describe rare diabetes study 1
20 week scan identified complex congenital heart disease
Mother had previous miscarriages
Birth weight: 1.8kg
ECG: transposition off great arteries, cyanotic
Had cardiac surgery
Day 8: developed jaundice
Day 11: hyperglycaemia, metabolic acidosis
Insulin infusion
What was the diagnosis of rare diabetes study 1?
GATA6 mutation
A transcription factor
Why are transcription factors important?
Necessary for beta cell development