Diabetes Flashcards
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?
GLUT 4
Which glucose transporter is present on beta-islet cells?
GLUT 2
Which glucose transporter is responsible for dietary uptake in intestines?
SGLT1
Which glucose transporter is found in the kidneys?
SGLT2
Are the GLUT transporters energy dependent?
No
Promote facilitated diffusion, not energy dependent
Are the SGLT transporter energy dependent?
Yes
Use sodium to move glucose against concentration gradient.
What are the substrates for gluconeogenesis?
Production of glucose from molecules (not carbohydrates)
Substrates are:
- 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
Glucose transport
GLUT 4 predominantly stored in intracellular vesicles
Insulin promotes fusion of vesicles and transporter insertion into cell walls
Thus facilitates glucose transport into cells
Glycogen synthesis Insulin promotes activation of glycogen synthase Other actions: Inhibit gluconeogenesis Glycogen synthesis Protein synthesis Lipogenesis Suppress ketogenesis
What are the actions of glucagon?
Promote gluconeogenesis Glycogenolysis Proteolysis Lipolysis Ketogenesis
