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41 Cards in this Set

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Insulin receptor (4 steps)
tyrosine kinase
phosphorylates IRS
which activates PI3-kinase
and Shc activated the Ras-MAP kinase pathway
PI3-K reaction
leads to phozs of downstream kinases
Akt leads to...
increased Glut4 in plasma membrane
some cases insulin can....
activate phosphateses which de-phos metabolic enzymes
Glucagon and epinephrine receptors...
are GPCR
increase cAMP levels
Insulin is a
prepro enzyme
pre is cleaved in ER
C-peptide removed by proteases.
Secretion of insulin (5)
1- Glu goes to beta cell by Glut2 and the phozsed by glucokinase.
2- Glucose metabolism increases ATP
3- ATP closes K channel
4 Opens voltage gated Ca++ channels
5- Influx of Ca activates kinases which phozs stuff leading to release of insulin
Insulin causes
tyrosine kinase to phosphorylate IRS and Shc
IRS binds
phosphatidylionsitol 3-kinase PI3-kinase
PI3- kinase consists
of p110 catalytic subunit and p85 reg subunit
p85 reg does
binds to phosphotyrosine of IRS which activates the p110 subunit
p110 products
are inositol lipids
the inositol lipids
activate enzymes including Akt.
Akt increase
movement of Glut 4 transporter to surface of adipose and muscle cells
insulin signaling ALSO activates
PP-1 which de phozs Gsk-3
GSK-3
blocks glycogen synthesis, and is inhibited by insulin so glycogen synthesis goes up
Akt ALSO activates
p70 which promotes protein synthesis
Shc...
activates mitogen activated protein kinase pathway that starts cell growth and differentiation MAP K pathway
Target organs for insulin
Liver
Adipose tissue
Muscle
Insulin in the liver...
INCREASES- Glycolysis, fatty acid synthesis, TAG synthesis, VLDL synthesis, glycogen synthesis, protein synthesis
DECREASES- gluconeogenesis, fatty acid oxidation, glycogen breakdown
Insulin in adipose tissue....
INCREASES glycolysis, fatty acid synthesis, TAG, TAG uptake from chylomicrons, VLDL
DECREASES- TAG hydrolysis
Insulin in the muscle
INCREASES- glycolysis, glycogen synthesis, protein synthesis
DECREASES- glycogen breakdown
Glucagon is
29 AA long peptide
released from pancreatic alpha cells
goes to liver and fat tissue
glucagon receptor
is 7 transmembrane G coupled (GPCR)
alpha subunit of G protein
coupled to GPCR and glucagon receptor GalphaS. It catalyzes dissociation of GDP from GalphaS and binds GTP
GTP bound GalphaS
dissociates from beta and gamma and stimulates adenylate cyclase.
adenylate cyclase
ATP to cAMP
cAMP binds to
protein kinase A PKA
PKA
phozs transcription factor called cAMP response element binding protein CREB
CREB
regulates expression of metabolic enzyme genes.
Metabolic effects of glucagon in liver
INCREASE- gluconeogenesis glycogenolysis fatty acid oxidation
DECREASE- glycolysis glycogen synthesis fatty acid synthesis
met effects of glucagon in adipose tissue
INCREASES TAG hydrolysis
Adrenal cortex
cortisol
adrenal medulla
epinephrine
Epinephrine binds ALSO
to GalphaS and increases cAMP levels(overlap with glucagon)
NOTE: they do not bind to each other's receptors and and EPI receptors on muscle and they are similar but not the same to glucagon in liver
Met effects of epi in muscle
increase glycogenolysis and glycolysis
Singulair
Montelukast

mon-te-LOO-kast
Cortisol in fat
TAG hydrolysis
cortisol in muscle
proteolysis
cortisol deficiency
addison's disease
chronic stress
decrease in muscle loss
redistribution of fat to abdomen
FFA not oxidized but deposited as visceral fat