Flashcards in Diabetes And The Pancreas Deck (20):
What are the common symptoms of type 1 diabetes and why?
Polyuria - glucose is filtered from the blood but it is not all reabsorbed so remains in the nephron of the kidney tubule. This means there is an extra osmotic pressure on the nephron and water less water is reabsorbed. Excreted as copious amounts of urine
Thirst - due to excess water loss and the osmotic effects of glucose on thirst centres
Weight loss - fat and protein are metabolised by tissues because insulin is absent
What are the markers before someone actually developed diabetes?
Genetic markers HLA DR3 and HLA DR4
What are the symptoms of ketoacidosis?
What causes ketoacidosis in type 1 diabetes?
High rates of beta-oxidation of fatty acids coupled with low insulin leads to the production of huge amounts of ketone bodies.
What are some symptoms of type 2 diabetes?
Lack of energy
Slow healing of minor skin damage
How is diabetes diagnosed?
-Random venous plasma glucose concentration >11.1mmol/L
-Fasting plasma glucose conc >7.0 mmol/L
-Plasma glucose conc >11.1 mmol/L 2 hours after 75g anhydrous glucose
One of these signs plus symptoms or
No symptoms and two of these signs.
Other than insulin, how can type 2 be treated?
Sulphonylureas - increase insulin release from the remaining beta cells and reduce insulin resistance
Metformin - reduces gluconeogenesis
What happens to glucose in persistent hyperglycaemia in some tissues?
Glucose + NADPH + H+ --> sorbitol + NAD+
Catalysed by aldose reductase
What are 3 macrovascular complications of diabetes?
Poor circulation the the peripheries - especially feet
What are micro vascular complications of diabetes?
Diabetic eye disease - changes in the lens due to osmotic effects of glucose (glaucoma), and cataracts. Diabetic retinopathy - damage to blood vessels leading to blindness
Nephropathy - diabetic kidney disease - damage to glomeruli, changes in kidney blood vessels and damage from urinary tract infections
Diabetic neuropathy - changes/loss of sensation, alteration in the function of the autonomic nervous system
Diabetic feet - poor blood supply, damage to nerves and increased risk of infection can contribute
In the pancreas, which cells produce insulin and glucagon?
Alpha cells - glucagon
Beta cells - insulin
What characteristics to cells which synthesise proteins for export have?
Extensive rough endoplasmic reticulum
Well-defined Golgi apparatus
Well-defined system of microtubules and micro filaments
What is the structure of insulin?
Two polypeptide chains - A and B
Held together by two disulphide bridges
Chain A has another disulphide bridge
How is insulin synthesised?
Synthesised on ribosomes associated with RER a pre-proinsulin
Signal peptide (pre) ensures insulin enters cisternal space of ER
Signal peptide then removed
Pro insulin folds
Transported to the TRANS Golgi apparatus and packaged into storage vesicles
C peptide removed by proteolysis from middle of chain
A and B chains held by disulphide bridges
How is insulin stored?
In storage vesicles along with the C peptide
Stored as crystalline zinc-insulin complex
What factors control insulin secretion?
Metabolites (glucose, amino acids, fatty acids)
Neurotransmitters (adrenaline, noradrenaline, Ach)
GI tract hormones (gastrin, secretin, cholecystokinin)
What is the structure of glucagon?
A single polypeptide hormone
Flexible 3D structure
What are the main actions of glucagon?
Increase gluconeogenesis in liver
Increase glycogenolysis and decrease glycogenesis in liver
Increase ketogenesis in liver
Increase lipolysis in adipose tissue
What is the mechanism of action of glucagon?
Binds to glucagon receptors on the cell membrane (GPCR)
This activates adenylate cyclase, increasing cAMP
High cAMP activates protein kinase A (PKA)
This phosphorylates and activates important enzymes