Pancreatic Endocrine Hormones Flashcards
delta cells =
somatostatin and gastrin
PP cells =
pancreatic polypeptide
which is more important…the ratio between insulin and glucago or their absolute concentrations?
ratio
insulin structure
2 polypeptide chains A and B
A chain = 21 aa
B chain = 30 aa
connected by 2 disulfide rings
insulin gene
3 exons and 2 introns
direct synthesis of preproinsulin
preproinsulin –> prosinsulin
cleaving N terminal signal peptide in RER
proinsulsin = A and B chains and C peptide
processing of proinsulin
in golgi (99%)…the rest is secreted
folds so A and B chains can link with disulfide bonds
remove C peptide and package into secretory granules
glucose transporter on beta cells
GLUT2
always expressed
glucokinase
phosphorylation of glucose in cytoplasm of beta cells
rate limiting step
oxidation of glucose –> how does it result in insulin release from beta cells?
ATP build up –> ATP-sensitive K+ channel closes –> K+ efflux is inhibited –> depolarization
–> VG Ca2+ channels open and influx of Ca2+ –> insulin release
relationship between plasma insulin and plasma glucose (graph)
sigmoidal
no insulin when below 50mg/dL
half max at 150
max insulin response = 300
property of insulin secretion
biphasic to a continuous glucose stimulus
within seconds of glucose exposure…immediate pulse of insulin that peaks at 1min and then returns to base
after 10min…second phase of secretion…which insulin increases more slowly then plateaus for many hours in normal people
which amino acids stimulate insulin secretion
Lys
Arg
prolonged exercise on insulin levels
decrease
circulation of insulin
unbound to any carrier protein
most important target tissues for insulin
adipose, liver, muscle
insulin receptor
2 alpha and 2 beta subunits
beta = transmembrane alpha = EC domains...alpha subunits are the ones that are connected (disulfide)
tyrosine kinase receptor***
steps once insulin comes in contact with its receptor?
- activate tyrosine kinase activity in beta subunit
- auto-phosphorylates the beta subunit
- phosphorylates tyrosine residues on insulin receptor substrates (IRS)
- IRS-1 and 2 = muscle, adipose, and liver
- IRS-3 = brain - IRS serve as docking and activating sites for other enzymes
- specifically PI-3 kinase –> creates PI-3 phosphates
- glucose transporters (GLUT4) are translocated to membrane….via action of Akt (called PKB or PKC too)
which key enzyme in adipose is inhibited by insulin
hormone sensitive lipase
glucagon structure
29 aa
residues 1-6 at amino terminus end are important biologically
precursor molecule for glucagon
preproglucagon
glucose and insulin effects on glucagon transcription
decrease
stress on glucagon release
increase synthesis and secretion
glucagon receptor
7 transmembrane G protein coupled receptor
acts through stimulatory G proteins (Gs) and therefore functions by increasing cAMP levels
in a normal state, insulin:glucagon a few hours a meal
2.0
in a fasted state or after prolonged exercise
insulin:glucagon
0.5 or less
effect of a high protein meal
increase both insulin and glucagon
insulin inceases uptake of amino acids into muscle and inhibits proteolysis
glucagon inhibits effects of insulin by increasing hepatic glucose output and decrease tissue glucose uptake…thus preventing hypogylcemia
regulation of synthesis of somatostain from delta cells
glucose, amino acids, fFAs, glucagons, various GI hormones
inhibited by insulin
somatostatin (-) secretion of what hormones
insulin and glucagon
and inhibits uptake of all nutrients from GI tract through inhibition of motility and secretion of most other GI hormones
