Diabetes Flashcards
Is insulin and anabolic or catabolic hormone? Describe what this means.
Anabolic This means it is an “add up” hormone - i.e. stimulates growth or development within a tissue
Which cells secrete insulin?
beta cells of Islet cells (islets of Langerhans) of the pancreas
What is the major action of insulin?
Insulin causes the up-regulation of GLUT-4 transport protein
Define: mitotic pathway
Mitotic pathways = encourage cell differentiation and growth. Insulin does this
At what stages of glycolysis does insulin work?
Reaction 1 (glucose –> glucose-6-phosphate)
Reaction 3 (fructose-6-phosphate –> fructose-1,6-bisphosphate)
Reaction 10 (phosphoinolpyruvate –> pyruvate)
What is the main function of insulin?
To drive glucose into cells and drives glycolysis
List the minor/alternative functions of insulin
- Inhibits nutrient breakdown (i.e. catabolism)
- Stimulates FA synthesis and esterification
- “store cupboard hormone” – storage of energy, repair and growth
Physiological effects of insulin - list the major stimulatory and inhibitory effects of the hormones
- Stimulatory*
- Glucose uptake into skeletal muscle and adipose tissue (GLUT-4 mediated)
- Amino acid uptake and protein synthesis (in muscle)
- Lipogenesis
- Glycogen synthesis
- Activity of Na/K ATPase pump
- NO synthesis & Renal Na reabsorption
- Inhibitory*
- Gluconeogenesis
- Proteolysis
- Lipolysis and ketogenesis
- Glycogenolysis
- Glucagon secretion
When are levels of insulin at their highest?
Post-prandially (i.e. after a meal)
Define hyperglycaemia
High blood glucose levels
- Normal ranges = 4-6 mmol/L during fasting*
- Diabetic ranges = >7 mmol/L during fasting *
What is a common cause of hyperglycaemia
Insulin deficiency (this is Type I diabetes)
List the osmotic symptoms of hyperglycaemia
- Polyuria – excessive urine
- Nocturia – urination at night
- Polydypsia – increased thirst
- Dehydration
- Pre-renal failure – acute kidney injury
How does the endothelium get damaged as a result of hyperglycaemia?
Oxidative stress occurs due to increases in glucose resulting in ROS.
ROS build up causes endothelial damage (most problematic in the glomerulus, eye and nerves)
How does hyperglycaemia affect ATP levels?
There is extracellular hyperglycaemia, but intracellular hypoglycaemia resulting in low ATP - consequence is that the cell must find alternative energy sources (eg: fats and ketones)
What are the consequences of mobilising fat stores and ketones?
- Mobilisation of adipose tissue to use fats (first triglycerides then free fatty acids)
- Eventually, amino acids will be used (substrate of gluconeogenesis – however, there is an insulin deficiency therefore it cannot be absorbed)
- Ketoacids are eventually used
- Utilised by CNS, synthesised in the liver (ketoacids –> actyl coA –> mitochondrial ATP)
- However in excess causes acidosis (specifically ketoacidosis) due to the production and build up of acetone and b-hydoxybutyrate
How does diabetes cause hyperkalaemia? What are the consequences?
Potassium enters the cell 1:1 with glucose
A lack of insulin = extracellular hyperkalaemia –> cardiac instability (action potentials) & muscle weakness
What is the link between insulin & cholesterol?
Insulin stimulates HMG CoA reductase activity –> increase de novo synthesis
How does having Type I diabetes affect cholesterol levels and overal CV health?
- Important in managing macrovascular risks
- Insulin deficiency leads to fall in cholesterol synthesis & LDL levels
- Treatment of Type I often leads to increase in HDL
- Mobilise cholesterol from peripheral cell membranes
- This appears healthy however, type I diabetics have increased CV risk
What is Type I diabetes
T cell mediated autoimmune destruction of beta cells resulting in absolute insulin deficiency
List the major epidemiological factors of Type I diabetes
- More likely to have it, if you have a pre-existing autoimmune condition (the converse is also true)
- Occurs mostly in younger people
- Degree of family history
List the short term effects of Type I diabetes
- Weight loss
- Osmotic symptoms
- Dehydration
List the long term effects of Type I Diabetes
- Blindness
- Renal failure
- Neuropathy (autonomic & peripheral)
What are the potential complications associated with type I diabetes?
- Untreated metabolic effects = hyperglycaemia, elevated free fatty acids, ketosis, hyperkalaemia, acidosis
- Elevated total cholesterol
- Retinopathy leading to blindness if left untreated
- Nephropathy (requiring dialysis)
- Neruopathy causing foot ulceration
- Disordered blood supply to lower limbs
- Large vessel disease (eg: atherosclerosis)
