Metabolic effect of Insulin / Glucagon Flashcards
Structure of Insulin
51 AAs in 2 polypeptide chains, A and B
2 disulfide bridges
intramolecular sulfide bridge between AA residues in the A chain
Insulin synthesis location
beta cells of islets of Langerhans
Pathway of insulin maturation
Preproinsulin ->ER -> Proinsulin -> Glogi -> Insulin + Cpeptide
Insulin degradation
in liver, kidney
by INSULINASE
halflife 6 min
Regulation of Insulin secretion
increased by: glucose, AAs, gastrointestinal hormones (CCK, gastric inhibitory polypeptide)
decreased by: epinephrine
Metabolic effects of insulin
glucose metabolism: -storage in muscle, liver, adipocytes -glycogen synthesis in liver, muscle -inhibits glycogenolysis, gluconeogenesis in liver lipid metabolism: -decrease TAG degeneration -increase TAG synthesis protein synthesis
Insulin receptor
alpha and beta subunits- tetramer
B: hydrophobic domain spans plasma membrane
A: extracellular- insulin binding site
B: cytosolic domain - tyrosine kinase
Signal transduction of Insulin
insulin binds to alpha subunit
conformational change to beta subunits
autophosphorylation
phosphorylation of insulin receptor subunits
Structure of Glucagon
29AAs in single polypeptide chain
Glucagon synthesis location
alpha cells of islets of Langerhans
preproglucagon -> glucagon
Regulation of Glucagon secretion
Increased by:low blood glucose, AAs, epinephrine
Decreased by: high blood glucose
Metabolic effects of Glucagon
Carbohydrate metabolism: breakdown in liver
Lipid metabolism: lipolyis
Protein metabolism: uptake of AA in liver
Mechanism of Glucogon
bind to G protein coupled receptor activation of adenylyl cyclase rise of cAMP activates cAMP dependent protein kinase phosphorylation