Diabetes Flashcards
Define diabetes
Metabolic disorder characterised by elevated blood glucose concentration either due to insulin resistance, insufficient insulin secretion, or both
What is the difference between Type 1 and Type 2 diabetes?
Type 1 = Insufficient secretion due to autoimmune destruction of Beta cells
Type 2 = Insulin resistance (loss of first phase insulin response and beta cell exhaustion)
What is the main metabolic fuel for the brain?
Glucose
Requires continuous supply due to inability to store or synthesise glucose in the brain
Where do we get our glucose supplies from?
Diet
Glycogenolysis (breakdown of glycogen)
Gluconeogenesis (formation of glucose)
Where does gluconeogenesis occur?
Liver and kidneys
What substrates form glucose in gluconeogenesis?
Glycerol (from fats)
Lactate (produced from non-oxidative metabolism of glucose - process reversed in liver in gluconeogenesis)
Glutamine and Alanine (from proteins)
What is glycogen?
Multi-branched polysaccharide
Energy storage molecule
Stored in liver and muscle cells
What are the main hormones that maintain glucose homeostasis?
Insulin
Glucagon
Where is insulin produced?
Beta cells (Islets of Langerhans within Pancreas)
What cells are found in Islets of Langerhans and what does each produce?
Alpha cells (produce glucagon) Beta cells (produce insulin) Delta cells (produce somatostatin)
What is the role of Somatostatin?
Inhibits action of insulin and glucagon
What are the phases of insulin secretion?
First phase = rapid onset, lasting approx. 10 minutes
Second phase = prolonged plateau lasting as long as necessary (e.g. whilst body is in hyperglycaemic state)
What occurs during the first phase of insulin secretion?
Release of pre-docked and primed vesicles
What occurs during the second phase of insulin secretion?
Release of insulin from granules - a complex process involving a process of transport, docking, priming and fusion
How do actions of insulin come about?
Activation of insulin receptors on target cell membrane which activates secondary pathway
What are the actions of insulin?
- Glucose transport
- Glycogen synthesis
- Protein synthesis and inhibition of protein breakdown
- Lipogenesis and inhibition of lipolysis
- Promotes mitogenesis (induces cell division)
How does insulin facilitate glucose transport?
Promotes fusion of vesicles containing GLUT-4 and insertion into cell walls to facilitate glucose transport into cells (by facilitated diffusion)
How does insulin facilitate glycogen synthesis?
Promotes activation of Glycogen Synthase
What regulates Glucagon secretion?
- Blood glucose levels - low blood glucose increases secretion and high blood glucose inhibits secretion
- Insulin secretion
What are the actions of Glucagon?
Stimulates gluconeogenesis and glycogenolysis
Increases hepatic fatty acid (beta) oxidation and therefore ketone formation
Stimulates lipolysis in adipose cells, increasing circulating free fatty acids and reduces adipocyte glucose uptake
What hormone is primarily responsible for responding to drop in blood glucose levels?
Glucagon
At what state is insulin favoured?
Post-pandrial (fed) state - insulin responding to increased glucose levels
How does the sympathetic nervous system alter insulin and glucagon levels?
Activation of sympathetic nervous system increases Adrenaline (and noradrenaline) release which inhibits insulin and promotes glucagon secretion
How does cortisol and growth hormones impact insulin and glucagon levels?
Promote gluconeogenesis
Inhibits glucose transport
Inhibits insullin secretion
