endocrine disorders ii albers
TRANSCRIPT
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Endocrine Disorders II: Albers 11/22/2010
Diabetes is essentially too much glucose in blood.
Insulin & Glucagon Review:
Insulin:
Released by -cells in the Islet of Langerhans region of the Pancreas
Lowers blood glucose levels
Ahormone that is released from the pancreas central to regulating
carbohydrate (glucose) and fat metabolism in the body.
Insulin causes cells in the liver, muscle, and fat tissue to take up glucose fromthe blood, storing it as glycogen in the liver and liver muscle.
Stimulates synthesis of triglycerides (TG) from free fatty acids (FFA) and stores it in adipose tissue;inhibits release of FFA from TG.
Glucagon
http://en.wikipedia.org/wiki/Hormonehttp://en.wikipedia.org/wiki/Carbohydratehttp://en.wikipedia.org/wiki/Fathttp://en.wikipedia.org/wiki/Liverhttp://en.wikipedia.org/wiki/Musclehttp://en.wikipedia.org/wiki/Fat_cellhttp://en.wikipedia.org/wiki/Glucosehttp://en.wikipedia.org/wiki/Bloodhttp://en.wikipedia.org/wiki/Glycogenhttp://en.wikipedia.org/wiki/Carbohydratehttp://en.wikipedia.org/wiki/Fathttp://en.wikipedia.org/wiki/Liverhttp://en.wikipedia.org/wiki/Musclehttp://en.wikipedia.org/wiki/Fat_cellhttp://en.wikipedia.org/wiki/Glucosehttp://en.wikipedia.org/wiki/Bloodhttp://en.wikipedia.org/wiki/Glycogenhttp://en.wikipedia.org/wiki/Hormone -
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A hormone secreted by -cells in the Islet of Langerhans region of the
Pancreas
Increases blood glucose levels
Major part is liver where it promotes:
Glycogen breakdown (catabolism)
Gluconeogenesis
From lactic acid and noncarbohydrates
Release of glucose from liver cells
Stimulates the release of FFA from TG
It also helps stimulates the release of insulin in a negative feedback
system
Recall that the Islet of Langerhans region is relatively small compared
to Pancreas
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Actions of insulin of the receptor:
Tyrosine kinase receptor mechanism
Insulin binds to receptor proteins
Dimerization of insulin receptor
Phosphorylation of receptor and makes Tyrosine kinase active Phosphorlyation of signal molecules-> cascade of
eventsglucose uptake and anabolic reactions
Diabetes
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Diabetes-insulin deficiency (and glucagon excess) increase in blood
glucose levelscomplications
Problems arrive from:
Producing insulin
Insulin action (function)
As a result of not having enough glucose uptake (cells not taking up
enough glucose), our bodies try to compensate by
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Increase mobilization of noncarbohydrate substrates to engage in
gluconeogenesis to produce more glucose
Protein breakdown formation of amino acids
TG breakdown into FFA
Pretty much, there US is getting more obese.
Theres an association/relationship between Obesity and Cases of
Diabetes
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Look in the dark blue, they are doing something that are increasing
their diabetic rate.
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In the yellow, it shows the normal levels of blood glucose levels
Hyperglycemia- high blood glucose levels
Stimulates insulin
Hypoglycemialow blood glucose levels(~ less than 60 blood
glucose/100ml)
Stimulates glucagon
In diabetes mellitus, notice that blood glucose levels are almost twice
as much.
Diabetics have glucose in urine- this is how you know theres too much
glucose levels in the blood
Type I Diabetes(aka. Insulin-dependent or juvenile onset diabetes)
chronic (lifelong) disease that occurs when the pancreas does not
produce enough insulin to properly control blood sugar levels.
-cells are destroyed
Type II Diabetes (aka. Non-insulin-dependent or adult onset diabetes
Insulin resistant
Body does not respond appropriately to insulin
Therefore, glucose isnt stored properly in fat, liver ormuscle cells for later use
Obesity
Metabolic size and demand may contribute to diabetes
Monogenic Diabetes(genetic causes)
Mutations of genes that causes diabetes
Affecting insulin producing mechanisms
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Insulin profile
In normal subjects:
With regards to eating a meal, there is going to have an acute
and abrupt increase in glucose levels, but it then goes back to
normal at a steady state.
Look at the difference between Type I and Type II diabetes
In type I diabetes:
No insulin produced from beta cell
flat line
In type II diabetes:
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-cell dis-function
not producing enough insulin
coupled with insulin resistance
red line shows mimics the normal subject, but there is no INITIAL
PEAK as a result of glucose intake.
Slow release of insulin
Dont have enough or any insulin to remove and bring back steady
state of glucose in blood
No -cell
Idiopathic (cause unknown)
Autoimmune
Own body produces antibodies against -cells in
pancreasimmune reaction elicit destruction of own -
cells
~ 10% of all diabetic cases Mostly childhood onset(some adult onset)
Typical therapy is to give insulin
Going back to Primary insulin effects:
Cant bring Glut-4 transporters to cell surface no glucose
uptake
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Question to ask Albers:
In type I diabetes, is there a defect in signaling Glut-
4 transporters?Why does he talk about Glut-4 transporters not being
able to surface.. maybe this is due to the lack of insulin.Because In type II diabetes, the insulin resistance shows a defect in a signal
to glut-4 to make it go to cell surface. Type I diabetes doesnt necessarily
mean there is a defect in the signal to Glut 4 because there is no insulin to
give the signal in the first place.
Glut 4:
Transport protein in fat and muscle cells
In a normal metabolism, insulin is secreted from pancreas and signals
fat and muscle cells to absorb glucose from the blood by binding to theinsulin receptors on the surface of the cells.
It goes to the cell surface after it gets a signal from insulin receptors
and transports glucose down into the cell down the concentration
gradient
Have diminished insulin being produced by -cell Insulin cant elicit biological affect at target cell because of the
unexplained resistance to insulin
In a nutshell, insulin resistance combined with a decrease in insulin
secretion= type II diabetes
Causes
Obesity
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As we get bigger, we put more metabolic demands
Putting more stress on bodies
More stress on insulin being produced
More stress on insulin working
Making people less sensitive to their own insulin
Excess in glucagon levels
Dont see so much of this
Inability of conversion of noncarbohydrates substrates into
glucose
No signal of Glut-4 to cell surface
Diet and exercise
The most advocated therapy for Type II diabetes
Diet- controlling glucose uptake
Exercise-
We can decrease our excess levels of glucose by increasesour metabolic demands of our muscles.
Facilitate availability of noncarbohydrate substrates
Type II diabetics can also benefit from insulin therapy
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Type 4 diabetes- occurs during pregnancy Complication of gestational diabetes
Size of baby
Mother have higher chance of having high blood pressure
during pregnancy
Growing incidence of diabetes and high blood pressure with
increasing age for mothers.
Mothers size also contributes to higher risk of diabetes and has a
higher chance of getting diabetes after giving birth
Baby isnt typically affected
Cant give a lot of drugs to mothers because of fear of what might
happen to babies
Should tightly monitor blood glucose levels
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Didnt really go over this, just know Gestational diabetes slide
Type 3 diabetes
All the other diabetes that are not type I, II, and gestational diabetesare grouped here as type III
It has to do with brain not being able to secrete insulin
Can be genetics, pancreatic disease, endocrine disorders like
Kushing Disease, drugs, infections, Turner syndrome
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Complications Diabetes:
Vascular effects
Influence blood flow to different parts of body(or extremities)
can cause compromised conditions
dealing with infections
injury
Macrovascular effect- myocardial infarctions (heart attack)
Microvascular effects
Blindness
Peripheral neuropathy Numbness
Sensation problems because of reduced flow of blood
Retinopathy-
Problems in vascularization in the eye
Decrease blood flow to eye effects vision
Nephropathy
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Decrease blood flow to kidney
Look at picture !
Why are diabetics always thirsty?
Increase of blood glucose
Can deal with it in kidney
A possible increase in ADH levels- makes us feel thirsty due
to ionic dis-equilibrium
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Diabetic Ketoacidosis-
A compensation mechanism that arises from lack of insulin
Leads to increased release of glucose by the liver(normally suppressed
by insulin) from glycogen and through gluconeogenesis.
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High levels of glucose levels goes into urine taking water and solutes(ie
Na+and K+) along with osmotic dieresis( increased urination due to the
presence of certain substances in the fluid filtered by the kidneys)
Leads to polyuria,, dehydration, and polydipsia(excessive thirst)
In the absence of insulin, it leads to the release of FFA from adipose
tissue, which again are coverted in the liver to ketone bodies to serve
as an energy source in the absence of insulin-mediated glucose
delivery, and is likely a protective mechanism in case of starvation.
The ketone bodies do have a low pH, therefore turning the blood
acidic.
Metabolic acidosis
Have major affects on compromised renal function(kidneys
are not able to remove enough acid to body, which can
result in academia(low blood pH) coma or death
The ketone bodies are an indication for the need to increase insubstrates for metabolism
Think about the Atkins diet
Removing carbohydrates from system
Eating only meats, fats, and vegetables
Removing sugar from body, as a result, the body will
compensate and produce ketone bodies. When you pee on
Ketone strips, and if there is an increase Ketone levels, the diet is
working.
The diet throws you in a state of diabetes in a way.
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Try to talk out this picture! Recall that primary substrate for brain is
GLUCOSE!
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Hypermolarity- increase in salt levels
Hyperlipidemia- high levels of lipids in blood stream
Osmotic dieresis- is increased urination due to the presence of certainsubstances in the fluid filtered by the kidneys
Diabetic foot ulcer
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Signature vascular impairment as a result of diabetes
Small problem can manifest because of inappropriate blood
supply.
Dont have to remember drugs but take into account that there are
different types of oral and insulin therapy
First line of defense to diabetes is diet and exercise (especially for type
II diabetes)
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Dont remember