Biochemistry Flashcards
(27 cards)
What is the normal level of blood glucose?
5mM
Which pancreatic cells are the main insulin producers?
Beta-cells
What is cleaved off proinsulin to yield insulin?
C (connecting) peptide
Insulin lispro has a lysine and a proline residues reversed. It is fast/slow and short/long acting
fast and short acting
Insulin glargine precipitates in the subcutaneous tissue. It is ______ acting. How many doses are required?
ultra-long acting
1 dose /day
What enzyme acts as a glucose sensor? How?
Glucokinase
- A small change in glucose concentration triggers a large increase in glucokinase activity
- Increased glucose metabolism increases ATP levels
- ATP inhibits ATP-sensitive K+ channels (Katp), causing cell membrane depolarisation
- Ca2+ channels open in response to depolarisation
- Ca2+ influx leads to fusion of secretory vesicles and insulin exocytosis
In T2DM the beta cells lose the ability to secrete insulin (T/F)
False
- insulin is produced
- hyperglycaemia means that glucokinase loses ability to respond to fluctuations in glucose concentrations
Release of insulin is biphasic. Why are there 2 phases of insulin release?
There are two insulin pools:
- Readily releasable pool (5%)
- Reserve pool - preparatory reactions are required for its release
Beta cells (in pancreas) only secrete insulin when they detect a fall in glucose below 5mM (T/F)
False
Beta cells produce insulin in response to high glucose levels, >5mM
T1DM results in the loss of beta cells (T/F)
True
-autoimmune destruction of beta cells
Sulphonylurea drugs (e.g. Tolbutamide) are used in T2DM treatment. What is their mode of action?
Katp channel inhibitors
- mimic action of ATP to depolarise beta cells
- depolarisation triggers insulin secretion
MODY (maturity-onset diabetes of the young) is a form of early onset _______ diabetes, characterised by defects in ______ ______ function and/or loss of _____ _____
Type II diabetes
defects in Beta cell function
and / or
loss of insulin secretion
What is impaired in MODY2? What are the implications?
Glucokinase mutations cause diminished sensitivity to rising glucose levels
-insulin is secreted at higher glucose levels
What are the glucose uptake channels in Beta cells?
GLUT2 channels
HNF Transcirption factors mutations are present in MODY 1 and 3. These TFs regulate differentiation and function of…
Beta cells
What is the purpose of genetic screening in diabetes?
Differentiate between MODY and Type 1 diabetes
1st line treatment for MODY is insulin injections (T/F)
False
-Sulfonylurea (induces secretion of insulin)
Insulin is ______ hormone. It therefore elicits what metabolic effects?
an Anabolic hormone
Induces:
- protein and DNA synthesis
- glucose and amino acid uptake in muscle
- lipogenesis in adipose and liver
- glycogen synthesis in liver and muscle
Inhibits:
- lipolysis
- gluconeogenesis
What type of receptor does insulin bind to?
What does insulin binding induce in the receptor?
Receptor tyrosine kinase
- Dimerisation of Beta subunits, which autophosphorylate themselves
- Activation of relay proteins (via phosphorylation)
Donohue syndrome (Leprechaunism) is associated with severe insulin resistance. It arises due to defects in _____ _____ or_____ ______ signalling
insulin binding or
insulin receptor signalling
List the symptoms of diabetic ketoacidosis.
Vomiting
Dehydration (thirst)
Increased HR
Ketone smell on breath
How are ketone bodies formed?
In liver mitochondria from acetyl-CoA - from Beta oxidation of fats
What effects does insulin have on ketone body production?
Decreases it by promoting glucose uptake by cells and inhibiting lypolysis
In what type of diabetes is Diabetic Ketoacidosis a possible complication?
T1DM
-insulin is low, thus there is a drive for lipolysis
