Control of glycogen metabolism & diabetes (lecture 29) Flashcards
what happens in the muscle during exercise?
high energy requirement glycolysis increases glucose uptake increase glycogen breakdown increases glycogen synthesis decreases
what happens in the muscle at rest?
low energy requirement glycolysis decreases glucose uptake decrease glycogen breakdown decreases glycogen synthesis increases
what happens in the liver after a meal?
high blood sugar
glucose release decreases
glycogen breakdown decreases
glycogen synthesis increases
what happens in the liver during fasting/exercise?
low blood sugar
glucose release increases
glycogen breakdown increases
glycogen synthesis decreases
what 3 hormones regulate glycogen metabolism?
epinephrine
glucagon
insulin
what does epinephrine do?
stimulates glycogen breakdown to fuel emergencies
glycogen breakdown increases glycogen synthesis decreases acts on muscle and liver cells acts via GPCRs initiates cAMP-dependent phosphorylation cascade
what do beta cells in the pancreas secrete?
insulin
what do alpha cells in the pancreas secrete?
glucagon
why are islet cells in the pancreas highly vascularised?
for glucose sensing
high oxygen and nutrient demand
what does glucagon do?
raises blood sugar levels
glucose release increases glycogen breakdown increases glycogen synthesis decreases gluconeogenesis increases increase in blood sugar levels
what does insulin do?
lowers blood sugar levels
glucose release decreases glycogen breakdown decreases glycogen synthesis increases gluconeogenesis decreases decrease in blood sugar levels
what does phosphorylation do to glycogen phosphorylase?
activates it
what does phosphorylation do to glycogen synthase?
inactivates it
how do epinephrine and glucagon act via GPCRs?
hormone binds
causes alpha subunit to bind GTP
activates adenyl cyclase
ATP converted to cAMP
PKA activated
• inactivates glycogen synthase a to glycogen synthase b to inhibit glycogen production
• activates phosphorylase kinase (b to a) which breaks down glycogen to glucose-1-phosphate
what does insulin act via?
receptor tyrosine kinase (RTK)
how does insulin act via RTK?
insulin binds to RTK
causes activation of insulin response substrate (IRS) by phosphorylation
activates protein kinases
inactivates glycogen synthase kinase
glycogen synthase kinase inactivates glycogen synthase
more active glycogen synthase
more glycogen synthesis
where is GLUT1 located?
all mammalian tissues
where is GLUT2 located?
liver and pancreatic beta cells
where is GLUT3 located?
all mammalian tissues
where is GLUT4 located?
muscle and fat cells
what does GLUT2 do?
mediates secretion of insulin by pancreatic beta cells when blood sugar is high
insulin vesicles are stored inside the beta cells ready to be exocytosed when given the right stimulus (glucose)
How do GLUT2 transporters causes insulin release?
1) glucose enters cell through GLUT2 transporter
2) glucose converted to glucose-6-phosphate
3) glucose-6-phosphate converted to pyruvate
4) ATP made closes ATP dependent K+ channels
5) causes depolarisation which causes the opening of vg Ca++ channels
6) insulin is exocytosed
what does insulin do to GLUT4 transporters?
stimulates transport of GLUT4 transporters to the plasma membrane of muscle and adipose cells
what is diabetes caused by?
problems with insulin signalling
what is type 1 diabetes?
insulin dependent diabetes mellitus (IDDM)
absolute insulin deficiency due to beta cell destruction
usually autoimmune
treatment
• exogenous insulin injection
• pancreas/islet transplant
what is type 2 diabetes?
beta cell hideaway to avoid death
reversible by diet and exercise
