Cell Signaling Pathways Insulin Flashcards
what does insulin do
reduce glucose levels
what does glucagon do
raises glucose levels
what is the most common form of carbohydrates ingested through diet
starch
what is the brains main source of energy
glucose
what are the types of carbohydrates in nature
polysaccharides, disaccharides, and monosccharides
what type of cells release insulin
beta cells
what type of cells release glucagon
alpha cells
what does phosphrylation do
reversibly turn an enzyme or receptor on or off altering its function
where does phosphorylation occur on enzymes or receptors
serine, threonine, tyrosine, and histidine
what is a kinase
an enzyme that phosphorylations by adding phosphate residues, uses ATP
what is a phosphatase
an enzyme that removes phosphate residues (desphosphorylates)
what does insulin do to glycogen synthase
activates protein phosphatase which dephosphorylates glycogen synthase and activates it
what does insulin do to glycogen phosphorylase
it activates protein phosphatase and dephosphorylates glycogen phosphorylase which inhibits it
what does glucagon do to glycogen synthase
it uses cAMP to activate protein kinase A which phosphorylates glycogen synthase which inactivates it
what does glucagon do to glycogen phosphorylase
it uses cAMP to activate phosphorylase kinase which phosphorylates glycogen phosphorylase which activates it
what happens in insulin biosynthesis
proinsulin is cleaved into insulin and C peptide
describe how insulin is released by the pancreas
-glucose is transported into beta cells by GLUT 2
-glucose goes into the glycolytic pathway to make ATP
- an increase ATP: ADP ration closes K+ channel causing depolarization
-this causes Ca2+ channels to open and Ca2+ stimulates the exocytosis of stored insulin. it also actives insulin gene expression via CREB
what is normal fasting blood glucose
70-130 mg/dL
describe the insulin receptor
a transmembrane receptor composed of alpha and beta subunits that belong to the family of tyrosine kinase receptors
what binds to and activates insulin receptors
IGF 1, IGF 2, and insulin
what happens when a ligand binds to the alpha chains of the insulin receptor
causes a conformational change that leads to autophosphorylation of tyrosine residues within the intracellular domain of the beta chain
what is the affinity of insulin receptors for insulin
high
what does the beta isoform of the insulin receptor bind
only insulin
what does the alpha isoform of the insulin receptor bind
IGF and insulin
what happens to GLUT4 when insulin binds to a receptor
GLUT4 secretory vesicles move GLUT4 receptors to the membrane
what does SGLT1 do
-mediates intestinal absorption of glucose from the diet on the luminal side of the intestinal enterocyte
- important in the glucose mediated secretion of incretin hormones, GIP and GLP 1
what does the GLUT2 receptor do
important for basolateral efflux of glucose into the blood stream
what are incretin hormones
gut hormones released after eating that stimulate the secretion of insulin by the beta cells of the pancreas
what are the major incretin hormones
GLP 1 and GIP
what are GLP 1 and GIP inactivated by
DPP 4 which is released from endothelial cells of blood vessels
what type of enzyme is the DPP 4 inhibitor
serine protease
what do DPP 4 inhibitors do
lead to increased insulin secretion and decreased glucagon levels and consequently improvement in hyperglycemia
describe the mechanism of action of GLP 1RAs and DPP4 inhibitors
oral intake of glucose get absorbed by the small intestine brush border. this increases GLP 1 and GIP. this binds to GLP 1RA in the beta cell which triggers the release of insulin and glucose uptake in fat and muscle . DPP4 also binds to GLP 1 and GIP in alpha cells to decrease glucagon and glucose production in the liver
how does insulin regulate lipolysis (lipid metabolism)
- glucose enters the beta cell which causes insulin release. insulin then binds to a receptor on an adipocyte. this causes a kinase cascade that causes phosphodiesterase to convert cAMP to AMP so fatty acids are not created and released
what happens to glucose levels when fatty acid levels are high
glucose levels are low and vice versa
how does acetyl- CoA carboxylase regulate FA metabolism
dephosphorylation of ACC stimulates production of precursors for fatty acid synthesis and one of these precursors, Malonyl CoA inhibits fatty acid beta oxidation
what adpator proteins does signaling via the insulin receptor involve
IRS 1 and IRS2 which transduce the signal via AKT and MAP kinases to effect changes in metabolic enzyme activity and gene expression
what is the effect of persistent hyperglycemia
damages number of tissues and organs
aside from blood glucose levels, what else does insulin affct
increases the rate of lipogenesis and glycogen synthesis to store glucose as glycogen or fatty acids
why does the brain use glucose as an energy source instead of fatty acids
- ATP generation from beta oxidation of fatty acids uses more oxygen than glucose which increases the risk of the cells becoming hypoxic
- beta oxidation of fatty acids generates superoxide which puts neurons under severe oxidative stress
- ATP generation from fatty acids stored in fat is slower than using blood glucose for fuel
