, PHYSIOLOGY
Neuroendocrine cells hypothalamus have axons up to posterior pituitary: secrete oxytocin,
ADH, hypophysiotropic hormones (control release anterior pituitary)
Hormone types:
Proteins and peptides hormones: hormones of anterior pituitary, parathyroid, glucagon and
insulin
o As preprohormones to RER become prohormones to golgi packaged as hormones in
vesicles till exocytosis
o Bind to receptor on membrane
o Freely carried in circulation, unbound so removed fast, short t1/2, by kidneys to
urine or by liver to bile
Steroids: by adrenal cortex (cortisol, aldosterone), estrogen, progesterone, testosterone
o Produced from cholestrol, not stored in vesicles but simple diffusion across
membrane
o Receptors in cytoplasm
o Carried in cirulation bound to proteins = longer t1/2, clearance by conjugation in liver
to bile
Derivatives from A.A tyrosine: thyroid hormone and adrenal medulla (epi and norepi)
o Receptors in nucleus
o Freely carried in circulation, unbound so removed fast, short t1/2, by kidneys to
urine or by liver to bile
Usually downregulation of receptors on target cell by high concentration hormone or hormone
binding; sometimes upregulation
Intracellular signaling:
Ion channel linked receptors
G-protein coupled: stimulatory or inhibitory (inhibits adenyl cyclase)
Enzyme linked hormone receptor: bijv. with leptin and insulin
o Receptor is enzyme itself: adenyl cyclae -> cAMP
o Receptor associated with enzyme (bijv. leptin receptor with enzyme binding site
inside cell -> tyrosine kinase JAK -> STAT)
Intracellular hormone receptor: steroid & thyroid -> hormone-receptor complex binds to
promoter DNA = hormone response element -> protein synthesis
o Thyroid hormone into nucleus to receptor = activate transcription factor itself ->
controls promoter gene in chromosomal complex
Second messenger mechanisms: bijv. with glucagon
cAMP: hormone binds to receptor, changes conformation -> activates G=protein -> adenyl
cyclase -> cAMP -> cAMP dependent protein kinase -> causes powerful amplifying cascade of
enzymes; so very little glucagon bijv needed for strong reaction
Receptor associated with phospholipase C -> catalyzes breakdown of phospholipid
membrane = 2nd messenger
Ca into cell binds to calmodulin
, DIABETES - PHYSIOLOGY
Islets of langerhans:
Alpha cells: glucagon -> 25%
Beta cells: insuline and amylin (inhibits insulin) -> 60%
o Insulin: 2 A.A. chains bound by di-S link, rest = C-peptides
o In ER: preproinsulin -> proinsulin, cleaved in golgi to become insuline
o Receptor: 2 alpha outside membrane, bound to 2 beta inside membrane associated
to enzyme --> tyrosin kinase -> phosphorylates IRS (insuline receptor substrate)
Delta cells: somatostatin
PP cells: pancreatic polypeptide
Insulin deficiency
abnormalities fat, synthesis protein problems (=tissue wasting), abnormalities carbohydrate
metabolism
Increase v.z -> cholestrol and phospholipids -> atherosclerosis
Increase beta-oxidation -> ketoacidosis
A.A stay in blood, urea increases
Insulin functions:
Uptake glucose from blood into cells
Inactiveert lever phosphorylase (dus geen glycogenolyse)
Activeert glucokinase: glucose -> G6P stored
Activeert glycogeen synthase
Inhibits gluconeogenese
Fat formation from glucose: glucose -> pyruvaat -> acetyl coA -> amlenyl coA -> v.z ->
itriglycerides packed into VLDLs to adipose tissue by lipoprotein lipase near tissue
o Citrate and isocitrate of czsnincrease amount of acetyl coA carboxylase which
convert acetyl coA to melanyl coA
o Increase lipoprotein lipase in capillaries around adipose tissue to take of fat
o Decrease hormone sensitive lipase which is inside fat tissue, hydrolyses triglycerides
already in fat cells to go back to blood
o Glucose uptake for v.z synthesis or for alpha-glycerophosphate -> glycerol
Insulin increases protein synthesis
Increases permeability of cells to A.A, K+, po4 3-
Insuline clearance: 50% by liver, 50% by kidneys
C-peptide: very little by liver, so stays in blood longer -> can be used to estimate rate of
insulin secretion, mainly by kidneys
Insulin reacts better on oral glucose than I.V because incretin effect -> GLP-1 and GIP incetins
in G.I cause anticipatory increase of insuline when oral glucose taken in + slow gastric
emptying + satiety
o Incretins are normally responsible for 60% of insulin secretion
o Incretins also stimulate lipogenesis (like insuline)
o Brief response b/c very short t1/2
Glucose utlization is 90% from glycogen liver and gluconeogensisi and 10% from
gluconeogensis kidneys; brain uses most glucose
Muscles:
Always use fat over glucose for metabolism between meals because no insulin between
meals so not enough glucose to take up except during:
Neuroendocrine cells hypothalamus have axons up to posterior pituitary: secrete oxytocin,
ADH, hypophysiotropic hormones (control release anterior pituitary)
Hormone types:
Proteins and peptides hormones: hormones of anterior pituitary, parathyroid, glucagon and
insulin
o As preprohormones to RER become prohormones to golgi packaged as hormones in
vesicles till exocytosis
o Bind to receptor on membrane
o Freely carried in circulation, unbound so removed fast, short t1/2, by kidneys to
urine or by liver to bile
Steroids: by adrenal cortex (cortisol, aldosterone), estrogen, progesterone, testosterone
o Produced from cholestrol, not stored in vesicles but simple diffusion across
membrane
o Receptors in cytoplasm
o Carried in cirulation bound to proteins = longer t1/2, clearance by conjugation in liver
to bile
Derivatives from A.A tyrosine: thyroid hormone and adrenal medulla (epi and norepi)
o Receptors in nucleus
o Freely carried in circulation, unbound so removed fast, short t1/2, by kidneys to
urine or by liver to bile
Usually downregulation of receptors on target cell by high concentration hormone or hormone
binding; sometimes upregulation
Intracellular signaling:
Ion channel linked receptors
G-protein coupled: stimulatory or inhibitory (inhibits adenyl cyclase)
Enzyme linked hormone receptor: bijv. with leptin and insulin
o Receptor is enzyme itself: adenyl cyclae -> cAMP
o Receptor associated with enzyme (bijv. leptin receptor with enzyme binding site
inside cell -> tyrosine kinase JAK -> STAT)
Intracellular hormone receptor: steroid & thyroid -> hormone-receptor complex binds to
promoter DNA = hormone response element -> protein synthesis
o Thyroid hormone into nucleus to receptor = activate transcription factor itself ->
controls promoter gene in chromosomal complex
Second messenger mechanisms: bijv. with glucagon
cAMP: hormone binds to receptor, changes conformation -> activates G=protein -> adenyl
cyclase -> cAMP -> cAMP dependent protein kinase -> causes powerful amplifying cascade of
enzymes; so very little glucagon bijv needed for strong reaction
Receptor associated with phospholipase C -> catalyzes breakdown of phospholipid
membrane = 2nd messenger
Ca into cell binds to calmodulin
, DIABETES - PHYSIOLOGY
Islets of langerhans:
Alpha cells: glucagon -> 25%
Beta cells: insuline and amylin (inhibits insulin) -> 60%
o Insulin: 2 A.A. chains bound by di-S link, rest = C-peptides
o In ER: preproinsulin -> proinsulin, cleaved in golgi to become insuline
o Receptor: 2 alpha outside membrane, bound to 2 beta inside membrane associated
to enzyme --> tyrosin kinase -> phosphorylates IRS (insuline receptor substrate)
Delta cells: somatostatin
PP cells: pancreatic polypeptide
Insulin deficiency
abnormalities fat, synthesis protein problems (=tissue wasting), abnormalities carbohydrate
metabolism
Increase v.z -> cholestrol and phospholipids -> atherosclerosis
Increase beta-oxidation -> ketoacidosis
A.A stay in blood, urea increases
Insulin functions:
Uptake glucose from blood into cells
Inactiveert lever phosphorylase (dus geen glycogenolyse)
Activeert glucokinase: glucose -> G6P stored
Activeert glycogeen synthase
Inhibits gluconeogenese
Fat formation from glucose: glucose -> pyruvaat -> acetyl coA -> amlenyl coA -> v.z ->
itriglycerides packed into VLDLs to adipose tissue by lipoprotein lipase near tissue
o Citrate and isocitrate of czsnincrease amount of acetyl coA carboxylase which
convert acetyl coA to melanyl coA
o Increase lipoprotein lipase in capillaries around adipose tissue to take of fat
o Decrease hormone sensitive lipase which is inside fat tissue, hydrolyses triglycerides
already in fat cells to go back to blood
o Glucose uptake for v.z synthesis or for alpha-glycerophosphate -> glycerol
Insulin increases protein synthesis
Increases permeability of cells to A.A, K+, po4 3-
Insuline clearance: 50% by liver, 50% by kidneys
C-peptide: very little by liver, so stays in blood longer -> can be used to estimate rate of
insulin secretion, mainly by kidneys
Insulin reacts better on oral glucose than I.V because incretin effect -> GLP-1 and GIP incetins
in G.I cause anticipatory increase of insuline when oral glucose taken in + slow gastric
emptying + satiety
o Incretins are normally responsible for 60% of insulin secretion
o Incretins also stimulate lipogenesis (like insuline)
o Brief response b/c very short t1/2
Glucose utlization is 90% from glycogen liver and gluconeogensisi and 10% from
gluconeogensis kidneys; brain uses most glucose
Muscles:
Always use fat over glucose for metabolism between meals because no insulin between
meals so not enough glucose to take up except during:
