Week 1/2 - A - Biochemistry of insulin Flashcards
Which hormone promotes the conversion of glucose to glycogen? Where is glucagon stored?
Insulin promotes the conversion of glucose to glycogen
Glucagon is stored in the liver, skeletal tissue and adipose tissue
What is the normal range for blood glucose?
Normal range is between 4 and 6
What cells of the pancreas are the endocrine pancreas? Which cells are the exocrine part of the pancreas?
Islets of langerhans - endocrine pancreas
Acinar cells - exocrine pancreas
What are the 4 cells of the endocrine pancreas and what do they secrete?
a cells - secrete glucagon
b cells - secrete insulin
delta (fancy S) cells - secrete somatostatin
PP cells - secrete pancreatic polypeptide
Which of the 4 pancreatic cells is the most abundant?
The beta cells secreting insulin
Where in the pancreatic B cells is insulin synthesised?
In the rough endoplasmic reticulum
Insulin is synthesised as a preprohormone in the rough ER of the beta cells, what is the name of this? What is preproinsulin cleaved to form?
Preproinsulin
Cleaved to form proinsulin + signal peptide
What is proinsulin cleaved to form?
Cleaved to form insulin and C-peptide in a one to one ratio
Insulin contains two polypeptide chains linked by what type of bonds?
Disulphide bonds
What chemical can often be used to measure the endogenous insulin levels? This can be done so though exogenous insulin, does not interfere with the insulin reading
Measure the C-peptide levels as they are form in a one to one ratio with endogenous insulin production
When glucose enters the pancreatic B cells, what transporter takes up the glucose?
GLUT2 - glucose transporter 2
When glucose is taken up by the GLUT 2 transporter, what is the enzyme that phosphorylates glucose to glucose-6-phosphate to make glucose ready for the process of respiration?
Glucokinase or hexokinase phosphorylates the glucose
Does glucokinase or hexokinase have a greater affinity for glucose?
Hexokinase has a greater affinity
Glucokinase only works at high glucose concentrations however has a greater Vmax
Once glucose enters the respiratory cycle, what does this increase the intracellular concentration of and what effect does this have?
Produces ATP which inhibits the ATP sensitive potassium channels
How does the inhibition of the ATP sensitive potassium channels lead to the release of glucose? (what fuses with cell membrane)
This leads to depolarization of the cell membrane causing the influx of calcium via the voltage gated calcium channels
The intracellular increase in Calcium concentration causing the fusion of secretory vesicles with the cell membrane and release of insulin
What two proteins does the Katp channel consist of?
An inward rectifier potassium subunit (Kir) - pore subunit – Kir6
A sulphonylurea receptor - regulatory subunit - SUR1
What type of structure does the Katp channel exist as?
It exists as an octomeric structure
(4xSUR & 4xKIR)
What effect does the sulphonylurea class of drugs have on the KATP channel?
KATP is directly inhibited by the sulphonylurea class of drugs, e.g. tolbutamide or glibenclamide
What class of drugs can inhibit insulin secretion by stimulating the Katp channels of the beta cells?
The diazoxides
What can cause congenital hyperinsulinaemia? What class of drugs can help here?
Mutations in the SUR1 subunit or the Kir6.2 subunits can cause this
Diazoxides can help decrease the insulin secretion
How does insulin control its own action of release via the negative feedback loop?
The secretion of insulin will lower the plasma glucose conecentration causing less glucose to enter the Bcells and therefore less secretion of insulin will occur
Insulin is important in controlling the storage of carbohydrates as a way of reducing blood glucose, How does it stimulate the uptake of glucose into cells? (what transporter)
Facilitates glucose transport into cells via glucose transporter 4 (GLUT4)
What are the other 3 ways in which insulin decreases plasma glucose concentration?
Stimulates glycogenesis (synthesis of glycogen from glucose)
Inhibits glycogenolysis (stops breakdown of glycogen into glucose)
Inhibits gluconeogenesis (stops the synthesis of glucose from non-carbohydrate precursors)
What is the insulin receptor?
Tyrosine kinase receptor
The insulin receptor is a dimeric tyrosine kinase What are the two subunits? What unit does insulin bind to? WHat links the two subunits?
Has two extracellular alpha subunits with insulin binding sites
Has two transmembrane beta subunits
The subunits are linked 4 disulphide bonds
What does the binding of insulin to the alpha subunit of the tyrosine kinase receptors cause?
causes the b subunits to phosphorylate themselves - autophosphorylation
Once the b subunits autophosphrylates itself, Insulin receptor substrates are phosphorylated Which pathway does this activate for glycogen synthesis?
IRS activate PI3K pathway for glycogen synthesis
What does PKB in the P13K pathway stimulate?
Stimulates GLUT4 translocation leading to the uptake of glucose by the cell - causes cell growth
when insulin not injected, cells fail to receive enough glucose and switch to fat breakdown What does this lead to a build up of and what condition can it cause?
Leads to a build up of ketones (by product of fat breakdown)
Leads to a condiiton called diabetic ketoacidosis
Is diabetic ketoacidosis normally associate with type 1 or type II diabetes?
Normally associated with type 1
