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Insulin signaling
When insulin binds, the insulin receptor phosphorylates itself and then
cytoplasmic proteins including the IRS family bind and the receptor
also phosphorylates the IRS tyrosine residues.
IRS proteins are docking proteins to which cytosolic SH2 containing
proteins bind to their phosphorylated tyrosine residues. These cyrosolic
proteins are often kinases and phosphatases and they are activated
upon binding to IRS
Insulin also activates the SOS/RAS pathway which activates the MAPK
pathway which is involved in the growth effects of insulin
Insulin also results in the upregulation of GLUT 4 transporters to the
membrane through IRS phosphorylation of kinase proteins that
activate GLUT4
Insulin also inhibits glycogen synthase kinase 3 (GSK3 normally
inhbibits glycogen synthase) thereby activating glycogen synthase
Effect of insulin on myocytes
GLUT 4 transporters to membrane to increase glucose uptake
Activates glycogen synthesis
Production of TAGs (lipogenesis)
Inhibits fatty acid breakdown
Uptake of amino acids and promotes protein formation
Inhbits protein breakdown
Oxidative metabolism
PEP CK
Insulin binds to receptor activates IRS -2 activates AKT (a kinase)
phosphorylates transcription factor Foxo thereby causing its
dissociation from DNA DECREASED transcription of PEPCK which is an
important enxyme in gluconegoen INHIBIT GLUCONEOGEN
Regulation of insulin
(+)Glucose, amino acids, and Ketones (remember ketone bodies are a
source of energy and in times of starvation the body will use them as
energy, insulin will also promote their uptake into muscle cells)
(+)GH (estrogens, ACTH , perhaps by increasing blood glucose thus
causing an indirect effect)
(+)Incretins (from GI)
(-) somatostatin
(+) acetylcholine
(-)NE/E
(+) calcium, sodium, potassium
(-) magnesium
Metabolism of insulin:
Degradation in liver/ kidneys by gluthione trans-hydrogenase and
proteases
Glucagon
Alpha cells
GLP-1 and 2 are formed in the alternative processing of proglucagon
molecule
Regulation
Glucose (-)
Fattty acids (-)
Amino Acids potentially stimulate? ?
Neuronal signals both parasympathetic and sympathetic (alpha 2 or
Beta 1) both (+) and berntal medial nuclei of hypothalamus
Nerve endings near alpha cells may stimulate thorugh epinephrine and
inhibit through seratonin
Hormones GLP-1 (-) and Cortisol STIMULATES (+)
Glucagon degradation
Proteolysis rapidly in many tissues
Short half life
Biliary and urinary excretion as well
Somatostatin
Delta cells, 14 aa peptide that inhibits both glucagon and insulin
Remember blood flows from center to periphery
Diabetes:
Negative nitrogen balance
Ketoacidocis
Osmotic diuresis