Endocrine pancreas Flashcards
Cells pancreas
A - glucagon
B - insulin - centre of islet
D - somatostatin
F - polypeptide
Insulin formation
polypeptide with disulphide bridges
made in rER and packaged in golgi
prepro
folded with disulphide bridges
proinsulin
c peptide detaches
insulin - then enters golgi and packaged into membrane bound granules
(c peptide measure of endogenous insulin production)
Insulin effects
seconds - K, glucose and AAs go intracelllar
Minutes - inhibits protein degradation, and gluconeogenic enzymes, activates protein synthesis and glycogen synthesis and glycolytic enzymes
hours - increases mRNA for lipogenic enzymes
Glucose transport
cells - fascilitated diffusion GLUT 1-7
intestines - secondary actie transport with Na (SGLT 1+2)
n.b. glut 4 mobilised to cell membranes by excercise - independent of insulin
Glucose receptor
extra cellular alpha
intracellular beta
TK domain activated
Glucose tolerance
decreased glut 4 expression
same glucose from GIT
same output from liver as no negative feedback
Normal glucose where it goes
50% CO2 and H2O
5% glycogen
40% fat
diabetes same glycogen, reduced everything else
hypoglycaemia –>
inhibits insulin secretion
glycogenolysis due to glucagon and adr
decreased peripheral use glucose due to growth hormone and cortisol (negligible)
Regulation insulin secretion
40 units/ day
glucose to b cell via glut2
broken to pyruvate via glucokinase
pyrvate to citric acid in mitochondria
oxidative phosphorylation
ATP reduces K efflux
B cell depolorised and exocytosis insulin
Sulphonylurea
blocks K channels B cells
therefore more depolarised and insulin release
e.g. gliclazide
SE hypoglycaemia
Biguanides
decrease gluconeogenesis in liver
SE lactic acidosis
e.g. metformin
Thiazolidinediones
increase peripheral glucose disposal (insulin mediated)
reduce insulin resistance
e.g. pioglitazone
cAMP
increased -> increased insulin
e.g. beta agonists and glucagon and throphyline
beta increases insulin, alpha decreases, overal decrease
Mechanism glucagon
in liver acts on GPCRs
adenyl cyclase -> cAMP -> pKA -> phophrylase -> glycogenolysis
also works via phospholipase C activation
Glucagon causes release of
GH and somatostatin release (an insulin)