Physiology And Pathophysiology Of Insulin Signalling Flashcards
Most important energy sources in mammals
Glucose and fatty acids
Only fuel source used by the brain
Glucose
Main hormone that lowers blood glucose
Insulin
Main hormone that increases blood glucose
Glucagon
Where is insulin produced?
Pancreas
Exocrine
released into hollow organs
Endocrine
released into bloodstream
What type of cell secretes insulin?
Beta cell
What kind of cell secretes glucagon?
Alpha cell
What do delta cells secrete?
somatostatin
What do F cells secrete?
pancreatic polypeptide
Glucose-induced insulin secretion
Glucose in bloodstream transported into cell on GLUT2
Metabolised to produce ATP
ATP inhibits ATP-sensitive K+ channels
Membrane depolarisation
Voltage-gated Ca2+ channels open & Ca2+ enters the cell
Fusion of pre-formed insulin vesicles with membrane
Releases insulin into bloodstream
Effects of insulin of cells
Increases glucose uptake
Increased conversion of glucose to glycogen
Diabetes mellitus
A group of metabolic diseases in which there are high blood glucose levels over a prolonged period
The disease is caused by the pancreas no longer producing enough insulin or cells becoming insensitive to insulin
2 methods of diagnosis for diabetes
Fasting plasma glucose test
Oral glucose tolerance test
Fasting plasma glucose test
Blood glucose levels tested after fasting for 8 hours -> 126mg/dL and above signal diabetes
Oral glucose tolerance test
After fasting for 8 hours, given a glucose drink. 2 hours later blood glucose levels measured -> 200mg/dL and above signals diabetes
4 main types of diabetes mellitus
Type 1 (insulin-dependent)
Type 2 (non-insulin dependent, maturity-onset, maturity-onset diabetes of the young)
Gestational diabetes
Secondary diabetes
Diabetes mellitus type 1
Insulin is absent or nearly absent because the pancreas either lacks beta-cells or has defective beta-cells
Usually arises from an autoimmune condition that selectively destroys beta cells
Typically develops over several years; symptoms only occur when >80% of beta cells are destroyed
Potential complications of type 1 diabetes due to daily insulin injections include
kidney malfunction
nerve impairment
cardiovascular disease
Potential complications of type 1 diabetes due to hyperglycaemia include
Blindness through retinal degradation and glycosylation of lens proteins, which causes cataracts
Diabetes mellitus type 2
Accounts for >90% of cases and affects ~20% of the population over 65
Complex mode of inheritance with interactions between several different susceptibility genes
Normal or greatly elevated insulin levels and symptoms usually arise as a consequence of insulin receptors not being fully functional. Mutations in insulin receptors are associated with the disease.
Strong link with obesity
Effect of insulin on cells
Increased glucose uptake, conversion of glucose to glycogen (for storage)
Metabolism in diabetes - why do diabetic patients produce large volumes of urine and drink a lot of fluids?
Glucose can’t enter cell due to lack of insulin or non-functional insulin receptors
Increased release of glucose by the liver via glycogenolysis and gluconeogenesis
Hyperglycaemia (high glucose bloodstream levels)
Blood plasma glucose exceeds renal capacity for reabsorption -> glucose present in urine
Glucose is osmotically active -> water loss (osmotic diuresis)
