Flashcards in Diabetes Deck (20)
Define diabetes mellitus
a heterogeneous complex metabolic disorder characterized by elevated blood glucose concentration secondary to either resistance to the action of insulin, insufficient insulin secretion, or both
What are the sources of glucose?
1) From dietary sources
2) From the breakdown of glycogen stores (glycogenolysis)
3) From formation of glucose (gluconeogenesis)
Which glucose transporters allow movement at low (basal) glucose levels?
GLUT 1, 3 and 4
Which glucose transporter is responsible for insulin dependent response in fat and muscles?
Which glucose transporter is present on beta-islet cells?
Which glucose transporter is responsible for dietary uptake in intestines?
Which glucose transporter is found in the kidneys?
Are the GLUT transporters energy dependent?
Promote facilitated diffusion, not energy dependent
Are the SGLT transporter energy dependent?
Use sodium to move glucose against concentration gradient.
What are the substrates for gluconeogenesis?
Production of glucose from molecules (not carbohydrates)
- Lactate (from non-oxidative metabolism – Cori cycle)
- Glycerol (from fats)
- Glutamine and alanine (from protein)
Where does gluconeogenesis occur?
Occurs in both liver and kidneys
How is insulin secreted?
Extracellular glucose is transported into the β -cell via GLUT-2.
Glucose is metabolised which increases adenosine triphosphate to diphosphate (ATP:ADP) ratio within the cell.
This leads to closure of ATP-dependent K+ channels
Closure of K+ channels leads to cell membrane depolarisation
Membrane depolarisation leads to opening of voltage dependent Ca2+ channels and Ca2+ influx
Ca2+ influx leads to exocytosis of stored insulin vesicles
What are the two phases of insulin secretion?
Insulin secretion occurs in two phases (biphasic):
- First phase has rapid onset and lasts ~ 10 minutes
- Second phase is prolonged plateau lasting as long as hyperglycaemia persists.
What are the actions of insulin?
Predominantly anabolic in action
Action via activation of insulin receptor on target cell membrane
Outcome depends on which secondary pathway is activated
GLUT 4 predominantly stored in intracellular vesicles
Insulin promotes fusion of vesicles and transporter insertion into cell walls
Thus facilitates glucose transport into cells
Insulin promotes activation of glycogen synthase
What are the actions of glucagon?
What happens in the post-absorptive state?
Post-absorptive (fasted) state
14-16 hours fast
Glucose levels relatively stable
Insulin : Glucagon ratio favours glucagon
Primarily catabolic state
Loss of insulin action to suppress lipolysis and proteolysis
Production of precursors for gluconeogenesis and production of other fuels (e.g. ketones)
What happens in the post-prandial state?
Post-prandial (fed) state
Insulin response to rising glucose levels
Acute exposure to free fatty acids also increases basal and glucose stimulated insulin production
Insulin : Glucagon ratio favours insulin
Primarily anabolic state
What do the L-cells of the small intestine produce?
L-cells of small intestine produce gastrointestinal insulinotropic polypeptides
- Glucagon-Like Peptides (GLP)
- Gastric inhibitory peptide (GIP)
Augment insulin secretion in response to oral glucose load.
What are the symptoms of Type 1 diabetes?