3: Insulin production, secretion and action Flashcards
Insulin helps with homeostasis of what?
Blood glucose concentration
What is the normal blood glucose concentration?
5mmol/L
What cells in the pancreas produce insulin?
Beta cells
What cells in the pancreas produce glucagon?
Alpha cells
The majority of pancreatic cells are acinar cells which secrete ___ enzymes.
digestive enzymes
Where specifically in a beta cell is insulin produced?
Rough ER
The precursor of insulin is a large chain polypeptide called ___.
preproinsulin
What activates insulin?
Cleavage of C peptide which is found in the middle of preproinsulin
Which bonds connect the two polypeptide chains of activated insulin?
Disulphide bonds
Which structure connect the two polypeptide chains for inactive proinsulin?
C peptide
Depending on the position of amino acids, insulin can be ___-acting or ___-acting.
short acting
long acting
Which type of insulin acts ultra-quickly and is injected by T1 diabetics 15 minutes before meals?
Lispro
Which type of insulin acts over an ultra-long period and is injected by diabetics at bedtime to maintain their blood glucose level overnight?
Glargine
What activates the secretion of insulin by beta cells?
Presence of glucose
By which transporter do glucose molecules enter beta cells?
GLUT2
Within beta cells, glucose is phosphorylated by ___ to form what?
glucokinase
Glucose-6-phosphate
In Type 1 diabetes, what happens to beta cells?
Destroyed by immune system
In Type 2 diabetes, why does insulin resistance develop?
Beta cells fail to sense glucose because they are constantly surrounded by it (hyperglycaemia), no longer produce insulin
What is produced by the metabolism of one molecule of glucose?
36 ATP molecules
When ATP is produced in a beta cell, what happens to
a) Potassium channels
b) Calcium channels
K+ channels close
Beta cell depolarises
Ca2+ channels open
Triggers secretion of insulin by exocytosis
Beta cells release insulin in response to blood glucose concentration rising above __ mM.
5 mM
In hyperglycaemia, the blood glucose concentration is (below / above) the KM of glucokinase.
What does this cause?
above KM of glucokinase
Over time, Type 2 diabetes:
hyperglycaemia > hyperinsulinaemia > insulin resistance > hyperglycaemia causing complications via Poyol pathway in a vicious cycle
Release of insulin occurs in ___ phases.
two phases
What percentage of insulin vesicles are immediately available for release from beta cells?
About 5%
The other 95% of insulin is released in the (first / second) phase of insulin release.
second phase
What type of drug mimics ATP to depolarise beta cells and trigger insulin release?
Sulphonylureas
-amides and -azides
What channel do suphonylurea drugs bind to?
Potassium channels
cause them to close - depolarisation due to lack of K efflux - Ca influx - insulin release
What drug has the opposite effect on potassium channels to sulphonylamides and is used to treat functional tumours like insulinomas?
Diazoxide
Mutations in the genes for the potassium channels of beta cells can lead to what type of diabetes?
What drug is used to treat this?
Neonatal / congenital diabetes
Sulphonylureas
What disease is caused by mutations affecting beta cell function and presents like T2 diabetes i.e problems with insulin secretion in young people?
MODY
maturity-onset diabetes of the young
In type 2 diabetes and MODY, what enzyme’s function is rubbish?
Glucokinase
What test allows you to tell MODY apart from Type 1 diabetes?
What is the difference?
How is each treated?
Genetic testing
MODY resembles T2 in that mutation affects K channels and glucokinase doesn’t work due to hyperglycaemia, T1 diabetes is an autoimmune disease destroying beta cells
MODY - sulphonylureas
T1 DM - insulin injections
By what process is insulin’s hormonal signal carried into a cell?
Signal transduction
What type of hormone receptor does insulin bind to?
Receptor tyrosine kinases
What is insulin resistance?
Change in cell sensitivity to insulin
can be caused by hyperinsulinaemia secondary to hyperglycaemia - cells are surrounded by insulin constantly so they stop responding to it
Insulin resistance is a result of problems with insulin ___ and ___.
insulin SENSING and SIGNALLING
What are the two main weight-related causes of insulin resistance?
Obesity (loads of adipose tissue)
Little/no adipose tissue
T2 DM has a multifactorial basis - what are these factors?
Genetic mutations
Obesity
Insulin resistance
What rare, autosomal recessive disease causes growth retardation, a strange facial appearance and absence of subcutaneous fat?
What causes it?
Leprechaunism / Donohue syndrome
Mutations in gene for insulin receptors, causing insulin resistance
What autosomal recessive condition has a stupid name and features acanthosis nigricans (hyperpigmentation)?
Rabson Mendenhall syndrome
Caused again by mutations for insulin receptors, causes insulin resistance
What is a fatal condition caused by uncontrolled diabetes?
Diabetic ketoacidosis
What are the symptoms of diabetic ketoacidosis?
Vomiting
Dehydration
Tachycardia
Sweet-smelling breath
Diabetic ketoacidosis is usually a complication of (Type 1 / Type 2) diabetes.
Type 1 diabetes
What are ketones produced by?
Fatty acid oxidation
What inhibits the oxidation of fat and prevents overload of ketone bodies?
Insulin
Ketones change the ___ of the blood.
pH
Fatty acids are converted into ___ ___.
If cells are “starved” of glucose, this chemical is then converted into ___ ___.
Acetyl CoA > Ketone bodies
Diabetic ketoacidosis usually occurs in Type (1 / 2) diabetes.
Type 1 diabetes
Untreated diabetic ketoacidosis leads to ___ and death.
coma
How is DKA treated?
Insulin
Rehydration
