Lecture 4 - Diabetes & Insulin secretion and intermediary metabolism Flashcards
What are the hormones that induce a reduction of glucose in the blood?
Insulin
Which hormones increase blood glucose levels?
Glucagon Catecholamines Somatotrophins Cortisol
What is the average value of glucose in the blood?
4-6 mmol/litre
What is the definition of T1DM?
Elevated glucose where insulin is required to prevent ketoacidosis
What is the definition of T2DM?
In terms of glucose but also related to hypertension and dyslipidaemia (elevated LDLs and decreased HDLs)
Which type of DM is more common?
T2
What type of diabetes are there?
T1, T2, Maturity onset of diabetes of the Young (MODY)
How do we treat diabetes?
Symptomatically, to avoid complications and mortality
Treatment for T1DM
Diet is important Insulin can be given physiologically Capillary glucose monitoring - as no physiological feedback loop
Hypoglycaemia is caused by..?
An imbalance of diet, exercise and insulin
Why is glucose important?
Acts as an energy substrate, especially for CNS (only uses glucose under normal conditions)
Definition of hypoglycaemia:
A blood glucose level of less than 4 mmol/litre
At what concentration can BGL cause unconciousness, coma and death?
> 2mmol/litre
What is most of the pancreas associated with?
Exocrine secretions via ducts
What cells are present in the Islets of Langerhans?
Alpha, Beta and Delta cells
How are the IoL set out?
3 adjacent cells all have tight junctions - form small intracellular spaces And gap junctions - allowing small molecules to pass between cells
What do the alpha cells release?
GLUCAGON
What do the beta cells release?
INSULIN
What do the delta cells release?
SOMATOSTATIN (all purpose -ve hormone)
How does somatostatin influence Growth and Development and BGL?
SS inhibits the release of glucagon and insulin, hence means that growth and development is inhibited and bgl would increase (if insulin inhibited) and bgl would decrease (if glucagon inhibited)
How is insulin production regulated by the beta cell’s influences?
What is the function of Insulin?
Increases a.a. transport and protein synthesis
Decreases lipolysis Increases lipogenesis
*Increases glycogenesis, glycolysis and glucose transport into cells via GLUT4*
DECREASES BLOOD GLUCOSE
How is glucagon release regulated by the alpha cells’s stimulation?
What is the function of Glucagon?
Increases lipolysis, a.a. transport into liver
Increased gluconeogenesis and hepatic glycogenolysis
INCREASES BLOOD GLUCOSE
What is the mechanism for insulin release?
Glucose enter into cytoplasm via GLUT2 receptor Glucose is phosphorylated via Glucokinase and turned to G6P G6P causes ATP release, closing ATP sensitive K+ channels This causes VGCC to open, causing influx of Ca2+ Ca2+ causes vesicles to move to the membrane surface releasing the insulin out of the beta cell
How is insulin synthesised?
Insulin is formed from Proinsulin, which is looks like a C C-peptide insulin is the precursor, and when insulin is formed the C-peptide is cleaved, releasing the A and B chain which forms the insulin molecule
The chains are joined by sulphur bridges
What is Glucagon-Like Peptide-1?
Gut hormone which is secreted in response to nutrients in gut Transcription product of proglucagon gene, mostly from L cell Stimulates insulin, inhibits glucagon Increases satiety SHORT HALF LIFE - rapid degradation from dipeptidyl peptidase-4
What is the First Phase Insulin Release?
It switches off hepatic output It is a peak at the very beginning, which increases very rapidly and decreases rapidly and then plateaus
What kind of energy source is best for diabetics?
Complex carbs are best as it gives them enough time to break it down - 3 hours Diabetics have problems with refined carbs
What is the insulin receptor made up of?
It has alpha subunits above the membrane Beta subunits under the membrane The beta subunits have Tyrosine Kinase domains (can auto and cross-phosphorylate) - where phosphorylation of cell protein substrates
For glucose to enter RBCs…
No insulin is needed
How does T2DM work? - in relation to receptors
The actual receptor is normal in most diabetics The fault is with post-receptor signalling
