endocrine disorders ii albers

8/8/2019 Endocrine Disorders II Albers

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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

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