Pathophysiology of diabetes Flashcards
How do GLUT transporters work?
Facilitated diffusion, not energy dependent
Where are GLUT transporters found?
GLUT 1: Everywhere, provide basal glucose to all cells
GLUT 2: Beta-islet cells
GLUT 3: Mainly in neurons
GLUT 4: Adipose tissue and muscles
Which GLUT transporters work independently of insulin?
GLUT 1, 2 and 3
Which GLUT transporter is dependent on insulin?
GLUT 4, responsible for insulin dependent response in fat and muscles
How do the SLGT transporters work?
Sodium dependent glucose transporter, requires ATP.
Where are SLGT 1 transporters found? What is their role?
Intestines: responsible for uptake of dietary glucose
Where are SLGT 2 transporters found? What is their role?
Kidneys: responsible for glucose reabsorption
What substrates are used for gluconeogenesis?Where does it occur?
Production of glucose from molecules: lactate (non-oxidative metabolism), glycerol (from fats), glutamine and alanine (from protein)
Occurs in liver and kidneys
Where is glycogen stored?
Liver and muscles cells primarily
What are the functions of insulin?
Decrease glucose production and lipolysis, increase glucose utilisation
What are the functions of glucagon?
Increase glucose production and lipolysis, decrease glucose utilisation
What are the effects of adrenaline on glucose?
Increases glucose production and lipolysis, decreases glucose utilisation
What are the effects of cortisol on glucose?
Increases glucose production and lipolysis, decreases glucose utilisation
What are the effects of free fatty acids (FFAs) on glucose?
Increases glucose utilisation, decreases glucose production
What are the effects of growth hormone on glucose?
Increases glucose production and lipolysis, decreases utilisation
Where is insulin produced?
Beta cells of Islets of Langerhans within the pancreas
What are the functions of the Islets of Langherhans?
Provide pancreatic endocrine function 3 major cell types: -Alpha- glucagon -Beta- insulin -Delta- somatostatin (inhibitor of insulin and glucagon)
Describe the process of insulin secretion
Glucose enters the pancreatic Beta-cell via GLUT-2 and is metabolised to ATP increasing ATP:ADP ratio within the cell. This causes K+ channel to close leading to cell membrane depolarisation which activates calcium channels causing an influx of calcium into the cell which triggers release of insulin vesicles by exocytosis.
Describe the phases of insulin release
First phase: rapid onset, lasts approx 10 mins.
Release of pre-docked, primed insulin vesicles.
Second phase: prolonged, lasts as long as hyperglycaemia persists. Transport, docking, priming, fusion.
Describe the actions of insulin
Anabolic
Activates insulin receptor on target cell membrane- outcome depends on secondary pathway.
Facilitates glucose transport into cells by promoting the fusion of GLUT-4 intracellular vesicles into cell membranes.
Increases glycogen synthesis by promoting activation of glycogen synthase.
Promotes protein synthesis and inhibits breakdown
Promites lipogenesis and prevents lipolysis via hormone sensitive lipase.
Promotes mitogenesis- insulin like growth factor homology.
What regulates the secretion of glucagon?
Hypoglycaemia increases and hyperglycaemia inhibits.
Levels rise with fasting, exercise and physiological stresses (trauma, infection)
Suppressed by insulin secretion.
Describe the actions of glucagon
Stimulates gluconeogenesis and glycogenolysis
Increases fatty acid oxidation and ketone formation.
Stimulates lipolysis in adipose cells which increases circulation free fatty acids and reduces adipocyte glucose uptake.
How are blood glucose levels maintained in the fasted state? (14-16 hours fasting)
Catabolic state
80% of glucose provided by liver:
-50% from glycogenolysis, 50% gluconeogenesis
As fasting progresses this shifts: 90% gluconeogenesis by 48 hours.
Kidneys contribute by gluconeogenesis, amount is comparable to liver.
Describe the post-prandial state
Increased insulin and decreased glucagon.
Anabolic state
Acute exposure to FFAs increases basal and stimulated insulin production
