Liver and metabolism L10 Flashcards
Type 1 insulin dependent diabetes
Cannot survive without insulin
Mainly young, but increasingly observed later in life
Ketosis may lead to death
Autoimmune destruction of B cells of islets of Langerhans
Sometimes follows viral infections (mumps, rubella, measles)
Treatment: insulin injections
Classical symptoms of type 1 diabetes
Thirst, tiredness, weight loss
Polyuria
Hyperglycaemic coma
Metabolic consequences of type 1 diabetes
Blood insulin levels low despite high blood glucose, whereas glucagon levels are raised
Insulin: glucagon ration cannot increase even when dietary glucose enters from the gut
Low insulin: glucagon ration leads to induction of catabolic enzymes and repression of anabolic enzymes
Type 1 diabetes- the liver
Liver remains gluconeogenic because of high glucagon
Lactate and amino acids such as alanine from protein breakdown are main substrates for glucose production hence muscle wasting
Glycogen synthesis and glycolysis inhibited
Fatty acids from lipolysis enter liver and provide energy for gluconeogenesis
Excess acetyl CoA from fatty acid oxidation converted to ketone bodes and if not used sufficiently can rapidly lead to ketoacidosis due to accumulation of ketone bodies and H+ in blood
Type 1 diabetes- the muscles
Relatively little glucose entry into muscle and peripheral tissues because of insulin lack- hyperglycaemia
Fatty acid and ketone body oxidation used as major source of fuel
Proteolysis occurs to provide carbon skeletons for gluconeogenesis leading to muscle wasting
Type 1 diabetes- adipose tissue
High glucose concentrations in plasma but uptake of glucose diminished by loss of insulin
Low insulin: glucagon ration enhances lipolysis leading to continuous breakdown of triacylglycerol and release of fatty acids and glycerol into blood stream to support energy production in peripheral tissues and gluconeogenesis in the liver
Type 1 diabetes- plasma and urine
Constant production excess glucose while utilising less leads to hyperglycaemia
Glucose concentration exceeds renal threshold, excreted in urine with loss of water and development of thirst
Fatty acid synthesis greatly diminished; VLDL secreted by liver and chylomicrons entering from gut cannot be metabolised properly as expression of lipoprotein lipase is regulated by insulin
Results in hypertriglyceridaemia and hyperchylomicronaemia and susceptibility to cv event
Short term consequences
Hyperglycaemia and ketoacidosis characteristics of type 1 diabetes
Hyperosmolar hyperglycaemic state (non ketotic hyperosmolar coma) characteristc of type 2 diabetes
Long term life threatening consequences of diabetes
Predisposition to CV disease and organ damage
Retinopathy- cataracts, glaucoma and blindness
Nephropathy
Neuropathy
High concentration of glucose results in
Generation of ROS
Osmotic damage to cells
Glycosylation leading to alterations in protein function
Formation of advanced glycation end products which increase ROS and inflammatory protein
Two major tests for diagnosing diabetes
Fasting blood glucose levels
Glucose tolerance test
Fasting blood glucose levels test
After overnight fast a blood glucose value of 126mg/dl and above on at least two occasions indicates diabetes
Glucose tolerance test
Performed in morning after and overnight fast
Fasting blood sample is removed and subject drinks ‘glucola’ drink containing 75g glucose
Blood glucose then sampled at 20 min, 1 hour and 2 hour
Treating type 1 diabetes
Aim: Mimic normal daily insulin secretion
Endogenous insulin secretion normally peaks within one hour after a meal with insulin secretion and plasma glucose levels returning to basal levels within two hours of the end of the meal induced hyperglycaemia
Insulin treatment regimes
Premixed insulin
- requires less injecting
- timing of meals may be critical
Insulin and food taken at the same time
- greater flexibility for those doing shift work
- potential nocturnal hypoglycaemia
Rapid acting with short half life
- reduces potential for nocturnal hypoglycaemia
- more expensive
