Pancreas and Insulin: Hyperglycaemia and Hypoglycaemia Flashcards
What is glucose?
Ubiquitous energy source used by all tissues
What is excess glucose converted into?
Glycogen - ‘stored reservoir of glucose’ in the liver
Can the CNS substitute glucose?
NO - therefore delivery is critical
What level defines Hypoglycaemia?
<2.5mmol/L
blood glucose levels
What levels define Normoglycaemia? (fasted and fed)
3-5mmol/L (healthy fasting value)
7-8mmol/L healthy post-prandial (fed)
What levels define Hyperglycaemia?
> 10mmol/L sustained
diagnostic feature of people with diabetes
What is the principle hormone detected when blood sugar levels rise?
Insulin (released from pancreatic Beta cells)
What does insulin do?
Acts on numerous tissues to bring sugar levels down and to restore homeostasis (negative feedback)
What causes the rise of blood glucose?
- food intake
- converting of fatty acids and amino acids into glucose precursors in the liver
- converting glycogen into glucose
What causes the fall of blood glucose?
fasting/overnight fast
What does the fall of blood glucose levels stimulate the release of?
Stimulates the release of glucagon from the islets of langerhans)
What does the release of glucagon do?
Stimulates processes mainly in the liver to increase blood glucose levels (also in muscles and adipocytes)
What is insulin?
A protein hormone (long chains of amino acids)
What is insulin derived from?
Proinsulin gene
Where is insulin synthesised?
Beta cells of the pancreas (islets of langerhans) in b cell secretory granules
What does insulin form a complex with and what effect does this have?
Forms complex with zinc - more zinc in insulin complex prolongs insulin action (used in the pharmaceutical industry)
What is the half life of insulin?
3-5 minutes
Where is insulin metabolised?
liver
Where are the islets of langerhans located?
In the pancreas (only compose 1% of the mass of the pancreas)
What cells make up the islets of langerhans?
β-cells (beta) α-cell (alpha) δ-cells (delta/D) ε-cells (epsilon) PP-cells
What do β-cells release?
Insulin
What do α-cells release?
Glucagon
What do δ-cells release?
somatostatin
What do ε-cells release?
ghrelin (seeks out food stuffs)
What do PP cells release?
Pancreatic polypeptide
When digestion increases blood sugar levels, where is glucose taken up and what happens to it afterwards?
Islet Beta cells. - then metabolised and cells depolarise because K channels close
What does depolarisation of islet beta cells cause an influx of?
Calcium, this causes insulin to be released (triggered by exocytosis)
What does insulin release directly correlate with?
Blood sugar levels
What do blood sugars stimulate the release of in the gut?
Hormones, such as GLP-1 (this pathway requires the Glucose uptake into B cells pathway to be active)
Where do the GLP-1 hormones act and what does it cause?
Act on the GLP-1 receptor on islet Beta cells which turns on cell signalling mechanisms ti release insulin
Where does insulin bind?
To insulin receptors in the liver
What happens when insulin binds to its receptor?
Insulin receptor when bound has kinase activity - sets off a cascade of other cell signalling mechanisms -one of those switches on transporters in the cell membrane and also causes the appearance of new transporters - Glut4 transporters - glucose enters the cell by facilitated diffusion down a concentration gradient and LOWERS blood glucose levels
What do insulin sensitizers do?
Help to facilitate the process of getting new glucose transporters at the cell membrane
Name the ways in which insulin lowers blood sugar (6)
- promotes hypoglycaemia
- increases transport of glucose into cells
- converts glucose to glycogen
- decreases glycogen breakdown
- increase fat stores
- increase protein production
What induces hyperglycaemia in diabetics?
Glucagon
What induces hypoglycaemia in diaebetics?
insulin
What is Diabetes Mellitus?
“Diabetes is a chronic disease, which occurs when the pancreas does not produce enough insulin, or when the body cannot effectively use the insulin it produces. This leads to an increased concentration of glucose in the blood (hyperglycaemia)”.
What happens to B cells in type 1 diabetes?
B cells are destroyed in type 1 diabetes - so therefore they cannot produce insulin
What is the problem in type 2 diabetes?
Insulin doesn’t act in the way it should - tissues aren’t sensitive to it.
What are the non-medical causes of hypoglycaemia?
inadequate, irregular food intake; insulin overdose; sulphonylurea overdose
What are the medical causes of hypoglycaemia?
insulinoma; hyperinsulinism; T1DM (nocturnal); post gastric-bypass hypoglycaemia; transient neonatal hypoglycaemia
What are the autonomic symptoms of hypoglycaemia?
hunger sweating shaking increased heart rate headache nausea
What are the neuroglycopaenic symptoms of hypoglycaemia?
confusion drowsiness odd behaviour incoherent speech poor co-ordination
What is glucagon therapy?
First aid treatment for severe hypoglycaemia when oral glucose is not possible or desired.
- injection
- must be reconstituted prior to use
- raises plasma glucose levels
What is Diazoxide therapy?
Oral administration, used in people with insulinomas.
Reverses the action of glucose on the Beta cell
used in hypos
Stops calcium coming in and stops insulin being released - causes massive hair growth
Why are hypoglycaemic events less likely in people taking an incretin agonist compared to sulphonylureas?
Incretins requires a rise in blood sugar for their actions to be medicated
Could an insulin sensitizer be co-administered with a secretagogue?
Yes
