Endocrine Flashcards
1
Q
endocrinology
A
study of biosynthesis, storage, chemistry, + physiological function of hormones secreted from endocrine glands or other tissues
study of hormones, their receptors, the intracellular signaling pathways invoked and the disease + conditions associated
2
Q
endocrine gland
A
lacks duct system
secretions are released into blood
ex. thyroid gland
3
Q
exocrine gland
A
has a duct system
secretions released into duct
ex. salivary gland
4
Q
endocrine + exocrine glands
A
ex. pancreas
has both
5
Q
types of cell communication
A
endocrine = release hormones into blood → target
neuroendocrine = hormone released by neuron
paracrine = effect on proximal cells
autocrine = self-stimulating
6
Q
endocrine signaling
A
hormone secretion by endocrine gland into blood
travels over long distance
slow in response
multiple target cells (less specificity)
7
Q
nervous system signaling (ex. paracrine)
A
NTs released by diffusion from secretory cell
acts locally (short distance)
fast in action
more target specific
8
Q
path for every hormone
A
- synthesis
- cell secretion
- storage/release + transport
- detection by receptors
- signal transduction + amplification of response
- changes in cellular response of target cell
9
Q
classification of hormones
A
based on structure:
→ site of receptor + mechanism of action
- solubility → water or lipid soluble
10
Q
proteins
A
water soluble
- small peptides ex. TRH, oxytocin, ADH
- polypeptides ex. insulin, glucagon, GH
- glycoproteins (CHO added) ex. FSH, LH, TSH
11
Q
lipids
A
lipid soluble
- steroids (from cholesterol) ex. cortisol, aldosterone, sex hormones
- eicosanoids (from arachidonic acid) ex. prostaglandings, leukotrienes
12
Q
monoamines
A
made from tyrosine
- catecholamines = water soluble ex. DA, NE, E
- thyroid hormones = lipid soluble ex. T3, T4
13
Q
protein hormone synthesis
A
- synthesis: preprohormone → prohormone
- packaging: prohormone → hormone
- storage
- secretion: hormone + any “pro” fragments
stored after synthesis + secreted when needed
14
Q
steroid hormone synthesis
A
cholesterol → pregnenolone → testosterone → estrogen
pregnenolone → progesterone → testosterone → estrogen
progesterone → aldosterone + cortisol
not stored, synthesized as needed
15
Q
water soluble hormones
A
peptide hormones + catecholamines
active after synthesis/secretion = quick acting
metabolism = inactivation
bind to cell surface receptors
16
Q
lipid soluble hormones
A
steroids + thyroid hormones
move through body bound to plasma proteins (inactive)
synthesis + metabolism control activity
bind to intracellular receptors
17
Q
target cell receptors
A
selectively recognize + bind specific hormones
binding of hormone = formation of hormone receptor complex → changes in target cell responses
cellular localization: cell surface or intracellular
18
Q
cell surface receptors
A
found in plasma membrane
fast metabolism
classified according to activation mechanism
- GPCR
- catalytic receptors
19
Q
GPCR
A
ex. adrenaline, glucagon
hormone = 1st messenger → carried by blood to receptor on cell surface
binding = form complex → activation of G proteins + membrane-bound enzyme
→ 2nd messenger → protein kinase → protein phosphorylation → response
amplification of signal: one hormone causes large response
20
Q
GPCR ex. vasopressin
A
G-protein cascade
membrane bound enzyme = Adenyl Cyclase
2nd messenger = cAMP
protein kinase = PKA
21
Q
GPCR ex. **
A
G-protein cascade
membrane bound enzyme = phospholipase C
2nd messenger = DAG
protein kinase = PKC
22
Q
GPCR ex. **2
A
G-protein cascade
membrane bound enzyme = ***
2nd messenger = Ca2+
intermediate = Ca2+/calmodulin complex
protein kinase = Ca2+/calmodulin dependent kinase
Ca2+ signaling via one of 2 ways:
- enters cell through Ca2+ channels during cell activation
- mobilized from storage by IP3 (activated by phospholipase C)
23
Q
amplification of signal
A
24
Q
catalytic receptors
A
ex. insulin, GH
hormone binds to transmembrane receptor = activation of tyrosine kinase
→ protein phosphorylation → response of target cell
25
catalytic receptors ex. insulin
receptor has TK domain in cytosol
autophosphorylation of tyrosine → phosphorylation of proteins
26
catalytic receptors ex. GH
binding of hormone to receptor = recruitment of activated TK
translocation of TK to receptor → phosphorylation of proteins
27
protein phosphorylation
important in cell signaling
protein kinase = either activation or inactivation of protein to turn on/turn off
protein phosphatase = hydrolysis (reverse phosphorylation) to either activate or inactivate protein
28
intracellular receptors
hormone binds receptor = ends up in nucleus + acts as transcription factors (bound to DNA)
alter gene transcription → synthesis of new proteins = response of target cell
slow metabolism
29
intracellular receptors in cytoplasm
ex. steroid hormone receptors in adrenal cortex
30
intracellular receptors in nucleus
ex. sex steroid receptors
31
intracellular receptors bound to DNA
ex. thyroid hormone receptors
32
up regulation
increase in number of receptors for a hormone
low amounts of hormone = use all to maximize response
33
down regulation
decrease in number of receptors for a hormone
prevent continuous activation
34
permissive action
hormone A must be present for full action of hormone B to occur (small effect in absence of A)
A may upregulate receptors for B on target cell
ex. thyroid hormone permits maximum effect of epinephrine
35
tropic (trophic) hormone
hormone that controls the secretion of another hormone
- hormone A signals release of hormone B from target cell
- hormone X signals increase secretion of hormone Y + stimulates growth of target cell Y
36
negative feedback control
dampen response
ex. PTH secretion + blood Ca2+
low Ca2+ triggers PTH release from endocrine cell → PTH targets bone/GI to ↑ Ca2+
→ negative feedback = ↓ PTH release
homeostasis = dampen significant changes in blood Ca2+
37
positive feedback control
amplify response
ex. small contraction/stretch in uterus initiates posterior pituitary secretion of oxytocin → signals uterine muscles to ↑ contraction + cervical stretch
= ↑ stimulation of posterior pituitary to ↑ oxytocin
amplify uterine contraction
38
hyposecretion
secretion of too little hormone
39
hypersecretion
secretion of too much hormone
40
hypo-responsiveness
reduced responsiveness of target cells due to:
- abnormal receptors ex. Laron dwarfism
- defective cell signaling
- defective enzyme function
ex. diabetes incepitus
41
hyper-responsiveness
increased responsiveness of target cells
42
pituitary gland
in midbrain
inferior to hypothalamus
contained in bony space
43
anatomy of hypothalamus + pituitary
hypothalamus → median eminence → pituitary stalk → posterior pituitary (anterior pituitary)
44
anterior pituitary
adnenohypophysis
frontal lobe of gland
neurosecretory neurons in hypot synthesize + release protein hormones into primary plexus (capillary bed fed by arterial blood) → hypothalamic-hypophyseal portal system (single blood vessel) → secondary plexus in ant. pituitary
hormone released → signals to endocrine cell = release hormone back into venous blood
45
posterior pituitary
neurohypophysis
posterior lobe of gland
neurosecretory neurons in hypothalamus extend through hypothalamic-posterior pituitary stalk to posterior pituitary = release of hormone into blood
46
hormones
ADH (39)
oxytocin (39)
GH (ant. pit.)
PTH
47
FSH
follicle stimulating hormone
released by anterior pituitary
targets ovaries and testes
stimulated by GnRH
48
LH
luteinizing hormone
released by anterior pituitary
targets ovaries and testes
stimulated by GnRH
49
ACTH
adrenocorticotropic hormone
released by anterior pituitary
targets adrenal cortex
stimulated by CRH
50
TSH
thyroid stimulating hormone
released by anterior pituitary
targets thyroid gland
stimulated by TRH
51
PRL
prolactin
released by anterior pituitary
targets mammary gland
inhibited by PIH
52
GH
growth hormone
released by anterior pituitary
targets most tissues
stimulated by GHRH + inhibited by SS
53
GnRH
gonadotropin releasing hormone
released by hypothalamus
targets anterior pituitary
↑ LH + FSH secretion
54
CRH
corticotropin releasing hormone
released by hypothalamus
targets anterior pituitary
↑ ACTH secretion
55
TRH
thyrotropin releasing hormone
released by hypothalamus
targets anterior pituitary
↑ TSH secretion
56
GHRH
growth hormone releasing hormone
released by hypothalamus
targets anterior pituitary
↑ GH secretion
57
GHIH
growth hormone inhibiting hormone (somatostatin)
released by hypothalamus
targets anterior pituitary
↓ GH secretion
58
PIH
prolactin inhibiting hormone (dopamine)
released by hypothalamus
targets anterior pituitary
↓ PRL secretion
59
hormones released by hypothalamus
peptide hormones
(exception: Dopamine)
60
hypothalamus-pituitary-target gland axis
input → hypothalamus = release of neurohormones → anterior pituitary = release of hormones → target gland = release of hormones
→ feedback systems
61
long-loop feedback system
negative
most body mechanisms
hormones released from target gland travel to anterior pituitary or hypothalamus + inhibit hormone release or the responsiveness of secretory cells
62
short loop feedback system
negative
anterior pituitary hormones signal target gland but do not cause other hormone release → also travel to hypothalamus to inhibit neurohormone release
ex. prolactin
63
posterior pituitary hormones
oxytocin + ADH
produced in the cell bodies of hypothalamus: paraventricular + supraoptic nucleus
carried by axons to posterior pituitary → released
64
growth hormone
most abundant anterior pituitary hormone
protein hormone
acts on cell surface receptors and is associated with protein kinase activity
secreted throughout life but slows with age
promotes growth mainly after birth
not secreted linearly (pulsatile)
follows circadian rhythm
65
GH effect on tissue growth
in vitro = no growth → doesn't cause tissue growth alone, works with other hormones
reproductive organs ↑ growth at puberty
brain growth occurs most between 0-8yo
total body height → two growth spurts ~after birth + 14 yo
66
bone growth
especially in long bones
growth in length = proliferation of cartilage cells at epiphyseal growth plates
fibroblasts differentiate into chondrocytes → proliferation in response to GH = cells build up layers (growth)
ossification as minerals are added → strength = bone
stops once growth plates seal
66
fibroblasts
progenitor cells (stem cells)
differentiate into chondrocytes
66
GH effect on metabolism
↑ aa uptake into cells → ↑ protein synthesis = ↑ growth of most tissues (cell hypertrophy + hyperplasia)
↑ lipolysis = ↑ free fatty acids (energy source)
↓ glucose uptake from blood into muscles (anti-insulin effects) = hyperglycemia
↑ gluconeogenesis by liver
66
chondrocytes
cartilage cells
proliferate during growth
deposition of minerals = ossification
67
hyperplasia
↑ cell division = ↑ number of cells in tissue
68
hormonal control of GH secretion
↑ by GHRH
↓ by somatostatin, GH (autocrine), IGF-1 (released from liver)
69
metabolic control of GH secretion
↑ by hypoglycemia, ↑ aas in blood
↓ by hyperglycemia, ↑ fatty acids
70
other controls of GH secretion
↑ by deep sleep, acute stress (ex. exercise)
↓ by prolonged malnutrition, chronic stress
71
gigantism
too much GH
onset in children
increased linear growth
72
acromegaly
too much GH
onset in adults
thickening of bone, large hands + feet + joints, coarse features
metabolic effects → hyperglycemia
73
dwarfism
too little GH
onset in children
caused by ↓ GHRH release from hypot or ↓ GH synthesis + secretion from pituitary
= no linear growth; metabolism effects → suppression of GH effect on blood glucose levels, lipolysis
74
Laron dwarfism
mutation of GH receptor
levels are normal but cells don't respond to hormone
75
ADH
antidiuretic hormone (vasopressin)
major source: supraoptic nucleus in hypot.
released in posterior pituitary
targets kidneys, blood vessels
stimulated by ↑ osmolarity in ECF or ↓ ECF/bp (hemorrhage)
76
↑ ADH release
changes detected by osmoreceptors in hypot or baroreceptors in hypot.
↑ production in hypot → ↑ release by post. pituitary
carried to kidney duct cells = ↑ water reabsorption + urine concentration
= ↓ ECF osmolarity or ↑ ECF vol/bp
77
SIADH
syndrome of inappropriate ADH secretion
too much ADH = ↑ water retention + blood vol
78
central diabetes insipidus
too little ADH due to problem in hypot.
large vol of dilute urine
79
nephroenic diabetes insipidus
too little ADH due to abnormal ADH receptors in collecting duct cells
do not respond to hormone signaling
large vol of dilute urine
80
oxytocin
major source: paraventricular nucleus in hypot.
released in posterior pituitary
targets uterus, mammary glands
stimulated by cervical stretch + suckling
81
adrenal glands
sits on top of kidneys
cortex (outside) + medulla (inside)
3 zones in cortex = each release different hormones
82
zona glomerulosa
releases mineralocorticoids = aldosterone
regulation of salt
83
zona fasciculata
releases glucocorticoids = cortisol
regulation of sugar
84
zona reticularis
releases androgens = DHEA and androstenedione
regulation of sex
85
adrenal androgens
sex hormones
less potent than testosterone
have no role in adult males
role in adult females, fetal development, puberty onset
86
synthesis of corticosteroids
cholesterol → progesterone → aldosterone + cortisol + adrenal androgens
87
aldosterone
↑ Na+ and water (second) reabsorption by kidneys
= increased retention by body
↑ K+ and H+ secretion by kidneys
= loss in urine
88
control of aldosterone secretion
↓ ECF blood vol/ ↓ bp / ↓ Na+
= kidney releases renin → cleaves angiotensinogen (from liver) into ATI = converted to ATII by ACE
ATII is carried to adrenal cortex = secretion of aldosterone
↑ K+ in ECF also signals cortex to ↑ aldosterone release
↑ K+ secretion = ↓ K+ in ECF → negative feedback to ↓ aldosterone release from cortex
= not under control of anterior pituitary tropic hormone
89
cortisol
affects metabolism of glucose
↑ secretion during stress conditions → maintain + protect body
permissive action on E and NE → exert control on vasc tone
= helps maintain blood pressure
90
actions of cortisol
1. vascular tone
2. metabolism
3. immune system
also effects during fetal + neonatal life
= development of CNS, GIT, adrenal gland, and surfactant in lungs
91
metabolic effects of cortisol
↑ blood glucose = ↑ availability for CNS
↓ glucose uptake in liver = prevent use by peripheral tissues
↑ gluconeogenesis in liver
↑ conversion of glucose → glycogen = storage
↑ protein + fat breakdown
92
immune system effects of cortisol
normal = suppression to prevent over activation → auto immune disease
too much = over-suppression
↓ lymphocytes, lymph node size
↓ humoral + cellular immunity
↓ production of inflammatory substances (ex. leukotrienes + prostaglandins)
↓ capillary permeability + prevention of neutrophil diapedesis to site of infection + edema
↓ proteolytic content release from lysosomes
= ↑ susceptibility to infection
93
pharmacological use of cortisol
suppress organ rejection after transplant
94
control of cortisol secretion
stress factors
diurnal rhythm affects hypot. release of CRH → stimulates ant. pituitary to release ACTH → stimulates adrenal cortex release of cortisol (fasciculata)
negative feedback on pituitary + hypot.
95
Conn's syndrome
too much aldosterone
hypernatremia (Na+ retention) → water retention = ↑ ECF vol = hypertension
hypokalemia (K+ secretion) → metabolic alkalosis
96
Addison's disease
too little aldosterone + cortisol
hypotension, metabolic acidosis, hyperkalemia
↓ blood glucose, ↑ skin pigmentation (↑ melanin)
97
Cushing's disease
too much cortisol
endogenous cause: overproduction bc of pituitary tumor, adrenal tumor, other cause
exogenous cause: too much glucocorticoid-containing medicine
↑ blood glucose, muscle wasting, ↓ resistance to infection
"moon face" = fluid accumulation causes round + puffy face
"buffalo hump" = fat deposition at back of neck
98
virilization
too much androgens
masculinization in females
99
too little androgens
↓ hair growth, ↓ sexual response in females
100
adrenal medulla
release catecholamines
E (80%) + NE
secretion regulated by sympathetic innervation of medulla - splanchnic nerve (preG) releases ACh onto chromaffin cells (postG) = release E + NE into blood
101
synthesis of catecholamines
tyrosine → DOPA → dopamine → NE → E
102
action of catecholamines
sympathetic response: short term stress
CV = ↑ hr, ↑ force of contraction, ↑ cardiac output, ↑ bp
smooth muscle = pupil dilation, bronchodilation, ↓ GI motility
metabolism = ↑ glycogenolysis, ↑ lipolysis, ↑ gluconeogenesis
103
thyroid gland
in front of trachea, butterfly shaped
follicular cells (thyrocytes) make up follicles → contain colloid
parafollicular cells sit in between follicles
104
follicle
resting (no stimulation) = thin, flat cells; filled with colloid
active = TSH trophic action → cells swell + secrete thyroid hormones
105
thyroid hormones
T3 and T4 (secreted from follicles)
synthesized from tyrosine and iodine
transported in blood mainly bound to TBP (small amount = free)
T3 is more potent (biologically active)
calcitonin (secreted from parafollicular cells)
106
thyroid hormone synthesis
1. thyroglobulin in synthesized in follicle cell + secreted to colloid = backbone for attachment of tyrosine rings
2. iodide is contransported with Na+ from blood into cell → diffuses across cell; moved into lumen by pendrin (transporter)
3. I- is oxidized + attached to tyrosine rings (1 I- = MIT; 2 I- = DIT)
4. iodotyronsines are coupled = T3 + T4 attached to TG backbone
5. when body needs T3/T4, molecule is endocytosed
6. lysosomal enzymes release T3 + T4 from TG backbone
7. hormones = lipid soluble → released into ISF → blood
107
TPO
thyroperoxidase = enzyme
under control of TSH
acts in oxidation of I- and coupling of MIT/DIT to DITs
108
T3 + T4
T3 = MIT + DIT
T4 = DIT + DIT
MIT = 1 I-
DIT = 2 I-
109
thyroid hormone secretion
neural inputs = ↑ TRH secretion from hypothalamus→ ↑ TSH secretion from ant. pituitary → ↑ thyroid hormone secretion from thyroid gland → target cells
= T4 (prohormone) converted to T3 in peripheral cells and liver
T3 binds to nuclear receptors
negative feedback of thyroid hormone on pituitary + hypothalamus
110
thyroid hormone actions
act on most tissues = changes in transcription + translation processes to synthesize new proteins
increase metabolism
required from growth and development
111
catabolic effect of T3
↑ breakdown of protein (muscles) + fat
↑ cholesterol metabolism
↓ serum cholesterol
112
anabolic effect of T3
↑ basal metabolic rate (=↑ O2 consumption + ↑ heat production)
↑ CHO absorption + utilization
113
TH actions: growth + development
act as tissue growth factors
small amounts stimulate protein synthesis
↑ GH/IGF-1 production
needed for CNS maturation during fetal stage
114
maternal hypothyroidism
poor fetal CNS development + mental developmental disability
115
permissive actions of TH
CV = targets beta-adrenergic receptors → ↑ hr and contractility, ↑ bp
SNS = targets beta-2 adrenergic receptors → potentiation
reproductive system = needed for normal function + fertility
116
Grave's disease
autoimmune disorder
overactivity of thyroid gland
TSH receptor antibodies stimulate thyroid hormone production (even in absence of TSH = continual tropic effect)
trophic effect in eyes + thyroid = ↑ cell growth
↑ BMR, weight loss, exophthalmos, goitre
117
Hashimoto's thyroiditis
autoimmune disorder
underactivity of thyroid gland
TPO antibodies destroy gland to block TPO action = no hormone synthesis
myxedema (weight gain, lethargy), cretinism (↓ growth in children)
118
symptoms of hypothyroidism
lethargy, weight gain, cold intolerance
constipation, nausea/low appetite, menorrhagia, edema
shortness of breath, dry skin, brittle hair + nails
myxedema madness
119
goitre formation
hyperthyroidsim: high T3 + T4 levels, low TSH levels
- antibody stimulation of gland causes topic + trophic effect (negative feedback = inhibition of TSH levels)
hypothyroidism (non-autoimmune cause): high TSH + TRH, low T3 + T4 levels
- low iodine in diet = unable to synthesize T3/T4 even with ↑ TSH = ↑ thyroglobulin → gland enlarges (no negative feedback)
120
best test for thyroid function
TSH measurement
changes in TSH occur before measurable changes in T3/T4
= reflection of true state of free T3/T4
121
iodine deficiency
from diet = most common cause of hypothyroidism, goitre, developmental/intellectual disability, preventable brain damage
North America consumes iodized salt = prevent deficiency
only need 150 ug per day
122
parathyroid gland
4 glands, embedded on posterior thyroid gland
chief cells secrete PTH
123
PTH
parathormone
peptide hormone
involved in calcium balance → [Ca2+] = more in ECF than ICF
↑ plasma [Ca2+] and ↓ plasma [phosphate]
124
calcium in body
99% stored in bone
1% = free Ca2+ + bound calcium
- 0.1% in ECF
- 0.9% in ICF
125
calcium
structural role - bone + teeth
blood coagulation
intracellular messenger
regulation of excitability
126
phosphate
structural role
metabolism (ATP, nucleic acids)
buffer (maintaining pH balance)
127
calcium balance
PTH = from parathyroid gland; targets bone
active vit D = from kidneys; targets GI tract
calcitonin = from thyroid gland; targets kidneys
128
bone
organic = collagen type 1
inorganic = calcium phosphate + hydroxyapatite
bone cells = oblasts, oclasts, ocytes
129
bone cells
osteoblasts: bone makers
osteoclasts: bone breakers
osteocytes: bone maintainers
130
resorption
breakdown of bone
by oclasts
bone remodelling process
131
hormonal regulation of Ca2+ balance
↓ plasma Ca2+ = ↑ PTH secretion from parathyroid glands
→ kidneys = ↑ Ca2+ reabsorption + ↑ active vitD formation
→ bone = ↑ resorption
restore plasma Ca2+ levels
132
control of PTH secretion
influenced by small changes in plasma [Ca2+]
low Ca2+ stimulates parathyroid endocrine cell to release PTH → target cell (bone; GI) = response to ↑ Ca2+ in blood
ideal Ca2+ level = neg feedback to parathyroid cells
133
synthesis of active vitamin D3
dietary vit D2/D3 or sunlight (converts 7-dehydrocholesterol found in skin to vit D3) = ↑ plasma vit D
25-hydroxylase in the liver = hydroxylation of vit D to 25-OH D → travels through blood to kidneys
1-hydroxylase in kidneys = hydroxylation of 25-OH D to 1,25-(OH)2D
stimulates GI tract to ↑ absorption of Ca2+ + phosphate into blood
134
1-hydroxylase
enzyme in kidneys
hydroxylation of 25-OH D to synthesize potent form of vitD
activity stimulated by PTH
135
VitD regulation of Ca2+ absorption
protein upregulation through transcriptional changes (enters cell + binds to receptor → translocation to nucleus)
- ECaC: epithelial calcium channel
- calbindin protein
- basolateral calcium pump
136
Ca2+ absorption
Ca2+ enters cell in duodenum through ECaC
binds to calbindin to diffuse across cell
crosses basolateral membrane by PMCA1 (Ca2+ ATPase pump)
137
rickets
deficiency of active Vit D
in children: deficiency in mineralization of bone matric = bones remain soft
- soft spot is slow to close; curved bones; large joints; bowed legs
138
osteomalacia
active vitD deficiency in adults
(similar to rickets)
139
hormones favouring bone formation
insulin
growth hormone
insulin-like growth factor-1
estrogen
testosterone
calcitonin
140
hormones favouring bone resorption
PTH
cortisol
thyroid hormones = T3 + T4
141
tetany
low plasma calcium increases nerve + muscle excitability via opening of Na+ channels
causes carpopedal spasm (sustained muscle contraction in wrist)
142
pancreas
islet of Langerhans = cluster of cells
alpha cells (15-20%) = glucagon
beta cells (55-90%) = insulin
delta cells (3-10%) = somatostatin
endocrine secretions
also pancreatic polypeptide and vasoactive intestinal polypeptide
143
insulin
feasting hormone
increases uptake + storage of fuels (glucose, triglycerides, amino acids)
anabolic
144
glucagon
fasting hormone
increases mobilization of fuels when needed
catabolic
145
target for insulin action
skeletal/cardiac muscle
adipocytes
hepatocytes
146
insulin actions in liver
↑ glycogenesis + ↓ glycogenolysis
↑ glycolysis + ↓ gluconeogenesis
↑ fat synthesis + ↓ fat breakdown
↓ ketogenesis
↑ protein synthesis + ↓ protein breakdown
147
insulin actions in muscle
↑ glucose uptake; ↑ glycogenesis
↓ glycogenolysis
↑ amino acid uptake
↑ protein synthesis + ↓ protein breakdown
148
insulin actions in adipose tissue
↑ glucose uptake
↑ glycolysis
↑ fatty acid uptake
↑ fat synthesis
↓ fat breakdown
149
activation of insulin receptor
150
glucose transport
insulin-sensitive GLUT-4 facilitated transport (independent of Na+)
insulin causes translocation of vesicles + insertion of transporters into membrane = glucose uptake
151
short-term glucose source
CHO = readily available in blood immediately after a meal
152
long term glucose source
glycogen (stored glucose) = broken down by glycogenolysis in liver
12-24 h after meal
post-absorptive phase
153
fasting: long term glucose source
gluconeogenesis = new synthesis of glucose from non CHO sources like aas and fatty acids
post-24 h
154
feasting: insulin effect on glucose
glucose is stored as glycogen in liver + muscle
155
feasting: insulin effect on fat
fatty acid synthesis in liver by acetyl-coA
triglyceride synthesis in adipose tissue
156
feasting: insulin effect on proteins
protein synthesis in liver and muscles
use amino acids
157
insulin deficiency
relative or absolute
associated with catabolic state = glucagon predominates
energy substrates are released from storage into blood
impaired glucose uptake into fat + muscle (90% of GLUT4 transporters are held intracellularly in vesicles)
- ↑ gluconeogensis
- muscle breakdown
- fat breakdown
158
fasting: glucagon effect on glucose
glycogen breakdown in muscle + liver
159
fasting: glucagon effect on fat
liver: glycerol → glucose; free fatty acids → ketone
adipose: lipolysis
muscle: fatty acids used for energy
160
fasting: glucagon effect on protein
liver: gluconeogenesis from aas
muscle: protein catabolism
161
blood glucose levels
net effect of hormone actions
insulin = decreased
glucagon = increased
162
control of insulin secretion
beta cells are stimulated to ↑ insulin secretion by:
- ↑ plasma glucose
- ↑ plasma amino acids
- incretins
- ↑ parasympathetic activity
inhibited by sympathetic activity = ↑ plasma epinephrine
163
hypersecretion of insulin
causes: pancreatic tumor, overdose
consequences: hypoglycemia → autonomic + hormonal response changes in brain
= ↑ sympathetic activity → palpitations, sweating
↑ production of counter regulatory hormones
tired, confusion, drowsy
convulsions, coma
164
hyposecretion of insulin
deficiency
- hyperglycemia
- diabetes mellitus
- ketoacidosis
165
type I diabetes
autoimmune disease
early onset
beta cells are destroyed
absolute insulin deficiency
~5-10% of cases in N.A.
166
type II diabetes
increased resistance to insulin
associated with obesity
relative insulin deficiency
more common in adults
~90% of cases in N.A.
167
insulin deficiency
leads to catabolic state
- hyperglycemia, wasting, acidosis, ketogenesis
= diabetic ketoacidosis
168
ketoacidosis
glucagon stimulates break down of stores in liver = production of ketones
severe metabolic decompensation leads to hyperosmolarity, dehydration, and death
169
polyuria
cardinal symptom of diabetes mellitus
↑ urine vol
↑ frequency of urination
170
glucosuria
cardinal symptom of diabetes mellitus
glucose in urine
171
polyphagia
cardinal symptom of diabetes mellitus
increased hunger
172
polydipsia
cardinal symptom of diabetes mellitus
increased thirst
173
chronic complications of diabetes mellitus
myocardial infarctions
hemorrhages
long term high levels of glucose leads to blindness, renal failure, atherosclerosis, changes in sensation, poor wound healing
174
type I treatments
administration of insulin
islet cell transplant
gene therapy
175
type II treatments
dietary control + exercise
drugs which ↑ insulin secretion + response to insulin
insulin administration
