Receptor Insulin

8/14/2019 Receptor Insulin

1/10

Hormone Location stimulation inhibition Mode of action effects Times of

secretion

Corticotr

opin

releasing

hormone

Paraventric

ular nuclei

of

hypothala

mus

Stress -secreted into the primary capillary plexus of

the hypophyseal portal system in the

median eminence of the hypothalamus

ACTH -anterior

pituitary

CRH -ACTH binds to receptor; g protein alpha

subunit activates adenylyl cyclaseincrease levels of cAMP

-cAMP activates protein kinase

-protein kinase activates cholesteryl ester

hydrolase which converts cholesteryl esters

(from LDL) into cholesterol

-cAMP also activates steroidogenic acute

regulatory protein which mediates the

transport of newly liberated cholesterol into

the mitochondria

-in the mitochondria and ER cholesterol is

converted into the steroid hormones

-steriodogenesis


2/10

Cortisol Adrenal

cortex:

zona

fasciculate

and zona

reticularis

-ACTH (produced

from cleavage of

POMC)

-stress

-in circulation, cortisolis bound to CBG

-disassociates from protein and diffuses

across cell membrane

-binds to cytoplasmic receptor causing

receptor disassociation from HSP70, HSP90,

and IP

-horome-receptor complex diffuses intonucleus and activates or inhibits

transcription

-time delay because mechanism of action

affects transcription

- CRH, and ADH

- in appetite

-maintain sensitivity to vasoconstrictors

- gluconeogenesis in liver

-fetal lung development

-ACTH

-GFR

- bone reabsorption

- insulin sensitivity

-immune system suppression

-collagen synthesis

Muscles

protein degradation

protein synthesis

glucose utilization

sensitivity to insulin

Liver

glycogen storage

gluconeo by activity and amount of

enzymes

Fat

glucose utilization

sensitivity to insulin

lipolysis (oxidation of fatty acids)

-high in

early

morning

-low in

late

evening

-when

change

sleeping

habits,

the cycle

changes


3/10

fat mobilization which their utilization

for energy

GHRH Ventomedi

al nucleus

of

hypothala

mus

GH

glucocorticoi

ds

-binds to receptor activating adenylyl

cyclase causing an increase in cAMP which

increases transcription to make new GH and

causes an influx of Ca to cause fusion of GH

secretory vesicle with membraneGH Anterior

pituitary

-amino acids

-starvation

-hypoglycemia

-exercise

-stage sleep

-gonadal

steroids/thyroid

hormone

-glucose

-GH

-IGF-1

-cortisol

-somatostati

n

-causes growth of almost all tissues

-promotes increased size of cell and

increased mitosis with devo of greater

number of cells

Adipose tissue

glucose uptake

lypolysis

adiposity

Fat used instead of carbs for E

-pulsatile

pattern


4/10

Liver

gluconeogenesis

IGF-1

Muscle

glucose uptake

amino acid uptake

protein synthesis

lean body mass

catabolism of proteins

IGF-1 liver GH Muscle

glucose uptake

amino acid uptake

protein synthesis

lean body mass

catabolism of proteins

Bone, heart, lung

protein synthesis

DNA, RNA expression

cell size/number

organ size

organ function


5/10

Chondrocytes

amino acid uptake

protein synthesis

DNA, RNA expression

collagen

chondroitin sulfate

cell size/number

linear growth

somatost

atin

hypothala

mus

IGF-1

glucocorticoids

-inhibits release of GH from pituitary

TRH Hypothala

mus

Stimulates release of TSH from pituitary

-activates phospholipase second messenger

system in pituitary to produce large amountsof phospholipase C, Ca2+, and DAG leading

to TSH release

TSH Pituitary TRH thyroid

hormone

1. TSH stimulates iodide pump on basal

membrane of follicular cell resulting in iodide

trapping

2. peroxidase on apical membrane oxidizes

iodide to iodine so it can readily bind to

tyrosine of thyroglobulin in the colloid

3.ER and golgi synthesize and secrete

thyroglobulin

4.in colloid, iodine binds with the aid of

iodinase to tyrosine residues of

thyroglobulin

5.T3 ad T4 are cleaved from thyroglobulin,

pinocytic vesicles grab chunks of colloids

6. lysosomes with proteases digest TG

releasing T3 and T4 that diffuse across the

base of the cell into capillaries

7. everything else is recycled back to the

-causes proliferation of thyroid gland

proteolysis of thyroglobulin stored in

follicles

activity of iodide pump

iodination of tyrosine t form thyroid

hormone

size and activity of thyroid cells

number of thyroid cells and change from

cuboidal to columnar


6/10

colloid

T4 and

T3

Thyroid

gland

TSH -circulates bound to proteins

-T3 binds thyroxine binding globulin and

albumin

-T4 binds thyrozine binding globulin,

albumin, and thyroxine pre-albumin

(transyrethin)

--slow onset and long duration of action

because tightly bound and acts through

transcription and translation

-at target T3 and T4 diffuse across

membrane

-T4 is deiodinated to T3 which is morebiologically active

-T3 diffuses into nucleus where it binds to

receptor which is bound as a heterodimer to

retinoid X receptor

-hormone bound receptor binds to hormone

response element

-results in increase or decrease in

transcription of genes

cardiac output, tissue blood flow, HR,

respiration, contractility

basal metabolic rate

mitochondria ( rate of formation of ATP

to energize cellular function)

Na/K ATPase (active transport of ions)

O2 consumption

glucose absorption/uptake

gluconeogenesis

glycogenolysis

lipolysis

protein synthesis

adrenergic responses (sensitivity to

sympathetic; beta receptor activity;

receptor numbers in

heart,liver,muscle,adipocytes, G alpha

expression)

-promote growth and devo of fetal brainInsulin Beta cells

of

pancreas

Glucose

Amino acids

Fatty acids

GH/cortisol

(indirect)

GI hormones

(amplifier)

somatostatin -synthesize as a preprohormone by RER and

then cleaved in ER to form proinsulinand

cleaved again in Golgi to form insulin and c

peptide

-insulin binds to receptor (4 subunits help

together by disulfide bonds)

-binding causes beta subunits to undergo

glucose transport by GLUT4 receptors

on membrane

protein synthesis (more permeable to

amino acid)

fat synthesis and storage

gluconeogenesis in liver

glycogen storage (inactivates liverphospholipase so no splitting of glycogen

-during

meals


7/10

Fed state autophosphorylation which activates

tyrosine kinase

-tyrosine kinase p-lates insulin receptor

substrates (intracellular enzymes)

glycolysis

growth and gene expression

Plasma

glucose

FFA

ketoacids

amino acids

Glucagon Alpha cells

of

pancreas

Amino acids

Acetycholine

Ep/NE

VIP

CCK

Fasting state

Glucose

Insulin

Somatostatin

Ketones

FFA

-activates adenylyl cyclase in hepatic cell

membrane

-increase in cAMP

-activates protein kinase which leads to de

p-lation and degradation of glycogen

releasing glucose

blood glucose

break down of glycogen

gluconeogenesis from a.a.

Glucagon

like

peptide

Gut Feeding insulin response to glucose; amplifier

beta cell mass

Leptin Released

from

adipocytes

Increased fat -acts on hypothalamus

-causes production of NPY and AGRP

-activation of POMC and alpha MSH

-CRH to food intake

-sympathetic activity

- insulin

satiety

hunger

Ghrelin Released

from GI

tract

fasting -acts within hypothalamus hunger Peak just

before

eating

and falls

after

meal

PTH Chief cells

of

parathyroid

Low plasma Ca High plasma

Ca

Ca binds to receptor which activates an

inhibitory g protein that decreases activity of

adenylyl cyclase and cAMP which decreasesPTH released

-Ca and PO4 resorption from bone

-Ca excretion from the kidneys


8/10

renal phosphate excretion that overrides

the resorption from bone

-stimulates formation of 1,25 OH2D3

GnRH Hypothala

mus

Progesterone

-possible

estrogen

-testosterone

-stimulates pituitary to release FSH and LH puslatile

LH Released

from

pituitary

-GnRH

Midcycle

-estrogen

Follicular

phase

-estrogen

Luteal

Phase

Progesterone

-hCG

-testosterone

-use cAMP messenger system

-acts on Theca cells resulting in the

production of androgens

-stimulates ovulation of ripe follicles and

formation of corpus luteum

-stimulates leydig cells to synthesize and

secrete Testosterone

-peak in

utero for

oogonia

devo

-surge

prior to

ovulation

FSH Released

from

pituitary

-GnRH

Midcycle

-estrogen

Follicular

phase

-estrogen

Luteal

Phase

Progesterone

-hCG

-inhibin

-uses cAMP messenger system

-acts on the granulose cells resulting in

synthesis of pregnenolone which is give to

theca cells and production of aromatse to

convert androgens that the theca produce to

make estradiol and estrone

-stimulates growth of follicle and estrogen

in females

-acts on sertoli cells to promote maturation

of sperm

-peak in

utero for

oogonia

devo

-peak 6

months

for final

sexualdifferenti

ation

Estrogen

s: -

estradiol;

estrone;

estriol

Ovaries,

corpus

luteum

FSH/LH -promotes proliferation and growth of

specific cells in the body responsible for

devo of secondary sex characteristics


9/10

-cause autocrine affects to first increase

sensitivity to FSH by increase receptors

and then icnreaseing LH receptos

cilia formation and activity of the oviduct

lining

contractility of muscular wall

proliferation of the endometrium

growth and contractility of the

myometrium

epithelial proliferation and glucogen

deposition in vagina

-watery secretion of cervical glands

-inhibits osteoclastic activity to promote

bone growth preventing osteoporesisprogester

one

secretion of oviduct lining

contractility of muscular wall

differentiation and secretion of

endometrium

contractility of myometrium

epithelial differentiation of vagina

epithelial proliferation of vagina

-dense, viscous secretion from cervical

glandshCG Placenta

(syncytial

trophoblast

cells)

-causes persistent corpus luteum to

prevent menstruation by continuing to

secrete estrogen and progesterone

-causes endometrium to continue to grow

and store large amounts of nutrients

Peaks

first

trimester

HCS/HPL Palcenta -partial development of breast and maybe

lactation in animals

-similar to GH but need lots of HPL to

promote growth

- insulin sensitivity and utilization of


10/10

glucose in mother making more available

for the baby (hyperglycemia)

-promotoes release of FFA from mom to

baby

Oxytocin Posterior

pituitary

Hypothalamus

-cervical stretch

receptors

-increases uterine contractions

-causes contraction of mammary gland

alveoli for milk let down

Prolactin Anteriorpituitary

Suckling

pregnancy

Dopamine -promotes milk production and secretioninto alveoli

Testoster

one

Leydig

cells

LH -enters cell, 5 alpha reductase converts to

DHT

-circulates bound to sex hormone binding

globulin

-causes transcription

-acts on sertoli cells to cause synthesis of

androgen binding protein which causes a

local testosterone sink that sucks up hugenumbers preventing it from escaping and

bathing developing sperm with huge

amounts of T because increasing bound T

increases free T so always in equilibrium

-secondary sex characteristics; external

genitalia, pigmentation, facial and body

hair, prostate, voice, libido, linear growth,

epiphyseal fusion

-fetal development of epididymis, vas

deferens, seminal vesicles

-pubertal growth of penis, seminalvesicles, musculature, skeleton, larynx

-spermatogenesis

Peaks 8

weeks,

one year,

and

puberty

DHT -activates transcription -fetal development of penis, penile

urethra, scrotum, prostate

-pubertal growth of scrotum, prostate,

sexual hair sebaceous glands

-prostatic secretion

Receptor Insulin

Documents

Transcript of Receptor Insulin