Download Insulin

Endocrine System
Part 2: Glucose Regulation
Glucose in Blood
 Glucose is an important fuel for cells
 Pancreas maintains blood glucose levels by
secreting hormones
Pancreas
 Exocrine system:
secretion of
hormones
through ducts
 Exocrine cells:
 98%-99% of
pancreas by mass
 Produce digestive
enzymes released
into small
intestine
http://media-2.web.britannica.com/eb-media/17/74317-004-9B143D52.jpg
Pancreas
 Endocrine
cells:
 1%-2% of
pancreas by
mass
 Scattered
throughout
the pancreas
 Islets of
Langerhans
http://media-2.web.britannica.com/eb-media/17/74317-004-9B143D52.jpg
Islets of Langerhans
 Alpha cells:
secrete
glucagon
 Beta cells:
secrete insulin
 Insulin and
glucagon are
antagonistic
hormones
http://www.rajeun.net/diabetes-pancreas.gif
Insulin
Insulin
 Stimulant:
 Blood glucose level rises above a set point
 Observed naturally after eating a meal
 Effect:
 Uptake of glucose by body cells through facilitated
diffusion by activating glucose transporters
 Inhibits the liver's breakdown of glycogen
 Inhibits liver’s conversion of amino acids and glycerol to
glucose
 Result:
 lowering blood glucose level
 decrease stimulus for insulin release
Glucagon
 Stimulant:
 Lowered blood glucose
 Glucose cleared from the blood stream
 Effect:
 Liver to increase breakdown of glycogen
 Liver convert amino acids and glycerol to glucose
 Result:
 Higher blood glucose level
 Decrease stimulus for glucagon release
Insulin Function
beta cells
hyperglycemia
insulin release
Increased glucose
uptake by cells
glycogen production
in liver
decreased blood
sugar
Glucagon Function
hypoglycemia
alpha cells
glucagon release
glucose released by liver
from non-carb source
glycogen breakdown in
liver releasing glucose
increased blood
sugar
Comparing Insulin & Glucagon
Situation
After a meal
Hormone
Insulin
Stimulant:
Blood glucose
levels
Effect: Glucose
uptake
Effect: Glycogen
breakdown
Between meals
Glucagon
Comparing Insulin & Glucagon
Situation
Hormone
Stimulant:
Blood glucose
levels
Effect: Glucose
uptake
Effect: Glycogen
breakdown
After a meal
Insulin
Increased
Increase
Decrease
Between meals
Glucagon
Comparing Insulin & Glucagon
Situation
Hormone
Stimulant:
Blood glucose
levels
Effect: Glucose
uptake
Effect: Glycogen
breakdown
After a meal
Insulin
Increased
Between meals
Glucagon
Decreased
Increase
Decrease
Decrease
Increase
Diabetes
 Common symptoms: frequent urination
 Types of diabetes:
 Mellitus (related to insulin and glucose)
 Type 1
 Type 2
 Insipidus (related to reabsorption)
Diabetes Mellitus Cause
 Type 1 diabetes
 Immune system attacks insulin producing cells
 Decreased insulin levels
 Type 2 diabetes
 Reasons not related to autoimmunity
 Decreased responsiveness of cells to insulin
 Inability of insulin to regulate blood glucose
levels
 Impairment of ability to remove glucose from the
bloodstream
Diabetes Mellitus Type 2
Diabetes Mellitus Types
Onset
Type 1
(Insulin dependent)
Childhood
Type 2
(Non-insulin dependent)
Adult (past age 40)
Pregnancy
Insulin resistance
(unresponsive receptors)
and deficiency
Obesity
Molecular
Cause
Insulin deficiency
Cause
Genetic
Autoimmune disorder
Treatment
Daily insulin injections Exercise & dietary control
drugs
Diabetes Mellitus Effect
 Glucose unavailable to body cells




Hyperglycemia: high glucose in blood
Excessive hunger
Fat used for cellular respiration
Increased blood viscosity and decreased blood flow


leads to blurry vision (poor blood flow in capillaries of retina)
foot infections (gravity cause blood to pool in feet)
 Kidneys start to excrete glucose
 Glucosuria: glucose in urine, “sweet” urine
 Frequent urination
 Persistent thirst
Canadian Connection
 Frederick Banting &
Charles Best
 Nobel Prize – 1923
 insulin isolation
 tied off ducts to digestive
tract
 cell producing digestive
enzymes shrivelled
 only islets of Langerhans
remained
Banting and Best
 Banting and Best began their experiments by
removing the pancreas from a dog. This
resulted in the following:
 It's blood sugar rose.
 It became thirsty, drank lots of water, and
urinated more often.
 It became weaker and weaker.
 The dog had developed diabetes.
 They then isolated “insulin” and injected it
back into the dogs and they seemed to be
cured.
Leonard Thompson
 January 1922 in
Toronto,
Canada
 14-year-old
boy was the
first to be
treated with
insulin
injections
Stress Regulation
What is Stress?
 The feeling of alarm or distress when reacting
to particular event
 Can be physical, emotional, cognitive or
mental
Stress Response
 Natural response
 Prepares an individual to handle the stressor
(an event that provokes stress)
 Types:
 Short term: responses are immediate
 Long term: responses are ongoing and can cause
detrimental side effects on the individual
Adrenal Gland
 Secretes stress response hormones
 Location: adjacent to kidneys
 Structure:
 Adrenal cortex : outer portion, involved with longterm stress response
 Adrenal medulla : inner portion, involved with
short-term stress response
Short Term Stress Response
Short-term Stress Response
 Stress excites nerve cells
to release a
neurotransmitter:
acetylcholine (ACh)
 Stimulates adrenal
medulla to release
catecholamines:
epinephrine and
norepinephrine
Catecholamines
 Synthesized from tyrosine
 Secreted in response to positive or negative
stress by the adrenal medulla
 Types:
 Epinephrine (adrenaline)
 Norepinephrine (noradrenaline)
Catecholamines
Tyrosine
Effects
 Stimulates the “fight-or-flight” response
 Increase metabolism
 Cellular respiration produces ATP
 Need energy source (glucose)
 Need oxygen
Effects: Energy Source
 Increased blood glucose levels
 Glycogen  glucose
 more ATP readily available
 Stimulates the release of fatty acids from fat
cells to supply the body with more energy
 Decreased kidney and digestive activity
Effects: Oxygen
 Increased blood pressure and blood flow
 oxygen is distributed to cells faster
 Increased breathing rate
 Relaxes/contracts certain blood vessels
 overall effect of redirecting blood away from nonvital areas
 increasing blood flow to the heart, brain, and
skeletal muscles
 Increased alertness
Short-term Stress Response
stress
Adrenal medulla
epinephrine
Breakdown glucose
Increase blood glucose
Increased blood volume,
pressure, breathing rate
Increased energy source
Increased oxygen
Fight or flight in
response to stress
Application
 Epinephrine is present in epinephrine
autoinjectors (EpiPens)
Long Term Stress Response
Long-Term Stress Response:
Neuroendocrine pathway
 CRH
 ACTH
 Corticosteroid
 Glucocorticoid
 Mineralcorticoid
Long-Term Stress Response:
Neuroendocrine pathway
Location
Stimulus
Hypothalamus
Hormone
Stress
Corticotropin-releasing Hormone
(CRH)
Anterior Pituitary Adrenocorticotropic Hormone (ACTH)
Adrenal Cortex
Corticosteroids:
Glucocorticoids (e.g. cortisol)
Mineralocoritcoids (e.g. aldosterone)
Effect
Increase glucose production
Increase oxygen delivery
Corticotropin-Releasing
Hormone (CRH)
 Neuropeptide hormone
 Released from hypothalamus
 Cause: stressful stimuli
 Stimulates anterior pituitary to synthesize
ACTH
Adrenocorticotropic Hormone
(ACTH)
 Polypeptide hormone
 Tropic hormone
 Produced from anterior pituitary
 Stimulates adrenal cortex to synthesize
corticosteroids
Corticosteroids
 steroids produced and released from the adrenal cortex
Type
Example
Glucocorticoid
Cortisol
Mineralcorticoid
Aldoesterone
Sex hormones
testosterone
Glucocorticoid (Cortisol) Effects:
Energy source
 Affects glucose metabolism
 Raise blood glucose levels by synthesizing glucose
from non-carbohydrate sources:
 Breakdown of fat to glucose
 Liver breaks down muscle protein in skeletal muscles to
glucose
 Occurs when body needs more glucose than what
the liver can produce from its storage of glycogen
 Other effects:
 Suppress immune system
 Natural anti-inflammatory (antihistamine)
Mineralocorticoid (Aldosterone)
Effects: Indirectly on oxygen
 Hormone that affects the body’s osmotic
balance
 Stimulates reabsorption of salt and water by
kidneys
 Cause increase in blood volume and pressure
 Increase oxygen delivery
Long-term Stress Response
stress
Hypothalamus
CRH
Anterior pituitary
ACTH
Glucocorticoid (cortisol)
Mineralcorticoid
(aldosterone)
Synthesize glucose from
non-carbohydrate source
Increased reabsorption,
blood volume, pressure
Increased energy and oxygen
for cellular respiration
Compare Short & Long Term
Stress Management
Stress
Hormones
Energy
Oxygen
Short term
Epinephrine
Norepinephrine
Long term
Glucocorticoid (cortisol)
Mineralcorticoid
(aldoesterone)
Glucose from
Glucose from nonglycogen stores
carbohydrate source
Increase heart
Increase reabsorption
rate, pressure, flow of salt and water, blood
& resp rate,
volume, pressure &
regulate vessel size flow
Stress Associated Disorders
Hypersecretion: Cushing’s Disease
 Overproduction of glucocorticoid (cortisol)
 Mimic diabetes:
 Hyperglycemia (high blood glucose)
 Glucosuria (glucose in urine)
 Protein shortage (protein converted to glucose)
 Cause: pituitary tumour (excess ACTH)
 Treatment: surgery, radiation
Cushing’s Disease
Physical Effects
 Excess glucose deposited as body fat in
abdomen, face, above shoulder blades
 Weight gain, “moon face” and “buffalo hump”
 Appendages remain thin
 Muscle weakness, prone to bruising
 Weak skeleton, prone to fractures
Cushing’s Disease
Physical Effects
 Effects also seen in people who take
glucocorticoids for other reasons
 Anti-inflammatory:
 Asthma
 Arthritis, joint injuries
 Immune suppressant:
 Lupus (autoimmune disease)
Karoshi
 “death from overwork” (Japan)
 Death from heart attack and stroke due to
stress
 Chronic increase in cortisol
Hyposecretion: Addison’s Disease
 Failure to produce adequate levels of
glucocorticoid (cortisol)
 Cause: autoimmune / adrenal gland disorders
 immune system gradually destroys the adrenal
cortex
 Treated with gluco/mineralocorticoids
Addison’s Disease Symptoms
 Characterized by several non-specific
symptoms:
 major weight loss
 dizziness, vomiting and nausea
 abdominal pain
 muscle weakness
 Notable case: US president John F. Kennedy