endo Flashcards
steps of insulin synthesis?
1) RER: preproinsulin synth
2) presignal cleaved –> proinsulin
3) storage in secretory granules
4) proinsulin cleaved –> exocytosis of insulin + C peptide
insulin intracellular signalling pathway?
1) binds tyr-kinase receptors –> tyr phosphorylation
2a) activates PI3 kinase pathway –> glucose uptake through GLUT-4, glycogen/lipid/protein synth
2b) activates RAS/MAP kinase pathway –> cell growth, DNA synthesis
how does insulin affect the kidneys?
causes increased Na retention
where do you find GLUT4 receptors?
adipose tissue striated muscle (exercise also increases GLUT4)
** ONLY insulin dependent glucose transporter
where do you find GLUT1?
brain, RBCs, cornea
where do you find GLUT2?
beta cells, liver, kidney, SI
** bi-directional
where do you find GLUT3?
brain
where do you find GLUT5?
spermatocytes
GI tract
** FRUCTOSE transport
regulators of insulin release?
1 = glucose
GH causes insulin resistance –> increased insulin release
beta2-agonists –> increased insulin release
glucose –> insulin release pathway in pancreas?
1) enters via GLUT2
2) glycolysis –> increased ATP
3) ATP-sensitive K channels close
4) depolarization –> voltage-gated Ca channels open
5) intracellular Ca –> insulin exocytosis
CRH has what downstream effects?
ACTH secretion
MSH secretion
beta-endorphin secretion
** CRH decreased in chronic exogenous steroid use
dopa/prolactin/GnRH/TRH interaction?
dopa inhibits prolactin
prolactin inhibits GnRH, stimulates dopa
TRH stimulates prolactin (and TSH)
what is tesamorelin?
GHRH analog
used to tx HIV-associated lipodystrophy
GH functions?
stimulates IGF-1 secretion –> linear growth and muscle mass
increases insulin resistance
GH regulation?
pulsatile release in response to GHRH
increased secretion in exercise and sleep
inhibited by glucose and somatostatin release
stimulates hunger and GH release?
ghrelin
made in stomach
** increased with sleep loss and Prader Willi
stimulates satiety?
leptin
made in adipose
- decreased in starvation and sleep deprivation
- mutation –> congenital obesity
V1 vs V2 receptors?
V2: ADH receptor for regulation of serum osmolarity
V1: ADH receptor for regulation of BP
** V2 mutation can cause nephrogenic DI
cholesterol desmolase fn?
conversion of cholesterol –> pregnenolone
first step in mineralocorticoid/glucocorticoid/sex hormone synthesis pathway
- inhibited by ketoconazole
- stimulated by ACTH
increased mineralocorticoids, decreased cortisol and sex hormones, hyperT, decreased androstenedione?
17-alpha hydroxylase deficiency
XY: pseudohermaphroditic
XX: no 2ary sex characteristics
increased sex hormones, decreased mineralocorticoids and cortisol, hypoT, increased K, increased renin and 17OHP?
21-hydroxylase deficiency - MC CAH
salt wasting or precocious puberty
XX: virilization
decreased aldo and increased 11-deoxycorticosterone, decreased cortisol, increased sex hormone, hyperT, decreased renin?
11beta hydroxylase deficiency
XX: virilization
** 11-deoxycorticosterone is cause of hyperT
cortisol immune functions?
inhibits leukotriene and PG production inhibits WBC adhesion --> neutrophilia inhibits mast cell histamine release reduces eos blocks IL-2 production --> reactivation of TB and candidiasis
pH and calcium levels?
increased pH –> increased albumin affinity for Ca –> hypocalcemic sx
D3 vs D2?
D3 from sun
D2 from plants
where is active form of vit D made, and what enzyme?
proximal tubule of kidney
1 alpha hydroxylase
vit D functions?
increased dietary Ca and P absorption
increased bone resorption –> Ca and P release
regulation of vit D production?
PTH stimulates
low Ca and low P stimulate
active vit D exhibits negative feedback
what is 24,25-OH2-D3?
an inactive form of vitamin D
where is PTH made?
chief cells of parathyroid gland
function of PTH?
increased bone resorption –> increased Ca and P
increased kidney Ca reabsorption (DCT)
decreased kidney P reabsorption (PCT)
increased active vit D conversion
mechanism of PTH stimulation of bone resorption?
increased production of macrophage CSF and RANKL
RANKL (made by OBs and osteocytes) –> RANK on OCs –> stimulates bone resorption
what does intermittend PTH release do?
stimulates bone formation
how does Mg affect PTH?
low Mg –> increased PTH release
VERY low Mg –> decreased PTH release
** causes of low Mg: diarrhea, aminoglycosides, diuretics, alcohol
where is calcitonin made?
parafollicular cells (C cells) of thyroid
which endocrine hormones signal via cAMP?
FSH LH ACTH TSH CRH hCG ADH (V2) MSH PTH calcitonin GHRH glucagon
** FLATChAMP (cgg)
which endocrine hormones signal via cGMP?
ANP
BNP
NO
** vasodilators!
which endocrine hormones signal via IP3?
GnRH oxytocin ADH (V1) TRH histamine (H1) angiotensin II gastrin
** GOATHAG
which endocrine hormones signal via intracellular receptors?
estrogen testosterone cortisol aldosterone progesterone vit D T3/T4
** adrenals + thyroid + vit D
which endocrine hormones signal via intrinsic tyrosine kinases?
insulin IGF1 FGF PDGF EGF
- activate MAP kinase pathway
- growth factors!
which endocrine hormones signal via receptor-associated tyrosine kinases?
prolactin immunomodulators GH G-CSF EPO thrombopoietin
- activate JAK/STAT pathway
- acidophils and cytokines
T3/T4 effects on heart?
increase B1 receptors –> increased CO, HR, SV, contractility
T3/T4 effects on BMR?
increase BMR via increased Na/K ATPase activity
what increases SHBG or TBG?
pregnancy, OCP use
what is the Wolff Chaikoff effect?
excess iodine temporarily inhibits thyroid peroxidase –> decreased iodine organification –> decreased T3/T4 production
what enzyme oxidizes/organifies iodide, couples MIT and DIT?
peroxidase
what drugs inhibit peroxidase?
PTU
methimazole
what converts T4 to T3?
5’ deiodinase
what drugs inhibit 5’ deiodinase?
PTU
