Insulin Secretion and Signalling Flashcards
What type of cells are in found i the pancreas
Alpha
Beta
S cells
PP cells
What do the beta cells do
Secrete insulin
What do alpha cells do
Secrete glucagon
What do the S cells do
Secrete somatostatin
What do the PP cells do
Secrete pancreatic polypeptide
Where and how is the insulin peptide structure synthesised
Int he RER of pancreatic beta cells as a larger single chain preprohormone - preproinsulin
Insulin peptide structure is cleaved to form what
Insulin
What does the insulin peptide structure contain
2 polypeptide chains linked by disulphide bonds
What type of product is the c peptide
A waste product with no known physiological function
Describe the variation in insulin amino acid sequence from species to species
Very little variation
What is used to avoid the problem of antibody formation
Human insulin instead of other animal insulin
How does Glucose enter the beta cells
Throughout he GLUT2 glucose transporter
What happens to the glucose when it enters the cell
it is phosphorylated by glucokinase
What cells sense the glucose levels in the blood
beta cells
Describe the relationship between the intracellular concentration to the extracellular concentration of glucose
Directly proportional
What will phosphorylate glucose at low concentrations
Hexokinase
What does a change of glucose concentration lead to
A dramatic change in glucokinase activity
An increased metabolism of glucose leads to what
An increase in intracellular ATP concentration
How many ATP molecules are produced per glucose molecule
36
What does ATP inhibit
The ATP sensitive K+ channel (KATP)
If the KATP is inhibited, what does this do to the levels of K+ in the cells
It increases it and causes depolarisaiton which will then result in the opening of the voltage gated claim channels.
If calcium is coming into the cell, what will be allowed
A release of insulin into the blood.
Inhibition of what leads to depolarisation of the cell membrane
Inhibition of KATP
What results in the opening of voltage-gated Ca2+ channels
Depolarisaiton of the cell membrane
What does an increase in internal Ca2+ concentration lead to
fusion of secretory vesicles within the cell membrane and release of insulin
what is the term used to describe the release of insulin
Biphasic
What is the RRP
Readily releasable pool of insulin
How much insulin granules are immediately available for release
5%
What 2 proteins do KATP channels consist of
Kir6.1 (inward rectifier subunit
SUR1 (a sulphonylurea receptor)
What are both Kir6.1 and SUR1 required for
To form a functional channel
How does intracellular ATP elicit depolarisation
By inhibiting KATP
KATP is directly inhibited by what class of drug
Sulphonylurea e.g tolbutamide or glibenclamide
KATP is stimulated by what? What does this do to insulin secretion
Diazoxide - it inhibits insulin secretion
If a patient has an overactive KATP channel, what are they most likely to have
Profound neonatal diabetes
If a patient has an inactive KATP channel, what are they most likely to be
Hyperinsulinaemic
What does MODY stand for
Mature onset Diabetes of the Young
What causes MODY
Mutations in at least 6 different genes
What play key roles in pancreas foetus development and neogenesis
HNF transcription factors
What else do HNF transcription factors do
Regulate beta cell differentiation and function
what is the main difference in treatment between MODY and type 1
Type 1 is treated with insulin
MODY is treated with sulphonylurea
What is the main problem in MODY
defective gluose sensing in the pancreas and/or loss of insulin secretion
What is the main problem in Type 1 diabetes
Loss of insulin secreting beta cells
What is the main problem in type 2 diabetes
Initially hyperglycemia with hyperinsulinaemia so primary problem is reduced insulin sensitivity in tissues
What is one of the major functions that regulates protein function in the cell
Protein phosphyorylation
this provides a reversible method for altering protein function
Where can proteins get phosphorylated
On any hydroxyl group
Insulin receptor is a what
Dimeric tyrosine kinase
Binding of insulin to the alpha subunits causes what
Beta subunits to phosphorylate themselves, thus activating the catalytic activity of the receptor
What is done through eh GLUT 4 pathway
Glucose transport into muscle and into fat
In what patients does the GLUT4 pathway not occur
Those with diabetes
What 7 different things does insulin effect
Amino acid uptake in muscle DNA synthesis Protein synthesis Growth responses Glucose uptake in muscle and adipose tissue Lipogenesis in adipose tissue and liver Glycogen synthesis in liver and muscle
Where are ketone bodies formed
In liver mitochondria
What are ketone bodies derived from
Acetyl-coA from beta oxidation
Why are ketone bodies important physiologically
They are molecules of energy metabolism for heart muscle and renal cortex
What are oxidised when glucose is not available
Fatty acids
What is converted to ketone bodies
Excess acetyl co-A
What can lead to acidosis
Accumulation of ketone bodies
What does a high glucose excretion cause
Dehydration and exacerbates acidosis
What can ketosis result in
Coma or death
What type of diabetes is ketoacidosis most associated with
type 1
