Endocrine Disorders II: Albers 11/22/2010

• Diabetes is essentially too much glucose in blood.

Insulin & Glucagon Review:

• Insulin:
• Released by β-cells in the Islet of Langerhans region of the Pancreas
• Lowers blood glucose levels
• A hormone 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 from
the 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
• A hormone secreted by α-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
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
eventsglucose uptake and anabolic reactions

Diabetes
Diabetes-insulin deficiency (and glucagon excess) increase in blood
glucose levelscomplications

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
• 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.

• There’s an association/relationship between Obesity and Cases of
Diabetes
• Look in the dark blue, they are doing something that are increasing
their diabetic rate.
• In the yellow, it shows the normal levels of blood glucose levels
• Hyperglycemia- high blood glucose levels
○ Stimulates insulin
• Hypoglycemia—low 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 there’s 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.
○ Β-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 isn’t stored properly in fat, liver or
muscle 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
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:
 • β-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

• Don’t have enough or any insulin to remove and bring back steady
state of glucose in blood
• No β-cell
○ Idiopathic (cause unknown)
○ Autoimmune
 Own body produces antibodies against β-cells in
pancreasimmune reaction elicit destruction of own β-
cells
• ~ 10% of all diabetic cases
○ Mostly childhood onset(some adult onset)
• Typical therapy is to give insulin
• Going back to Primary insulin effects:
○ Can’t bring Glut-4 transporters to cell surface no glucose
uptake
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 doesn’t 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 the
insulin 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 β-cell

• Insulin can’t 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
  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
 Don’t 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 increases
our metabolic demands of our muscles.
 Facilitate availability of noncarbohydrate substrates
• Type II diabetics can also benefit from insulin therapy
• 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.
• Mother’s size also contributes to higher risk of diabetes and has a
higher chance of getting diabetes after giving birth
• Baby isn’t typically affected
• Can’t give a lot of drugs to mothers because of fear of what might
happen to babies
○ Should tightly monitor blood glucose levels
 • Didn’t really go over this, just know Gestational diabetes slide

Type 3 diabetes

• All the other diabetes that are not type I, II, and gestational diabetes
are 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
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
 ○ 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
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.
• 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 in
substrates 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.
Try to talk out this picture! Recall that primary substrate for brain is
GLUCOSE!
Hypermolarity- increase in salt levels
Hyperlipidemia- high levels of lipids in blood stream
Osmotic dieresis- is increased urination due to the presence of certain
substances in the fluid filtered by the kidneys

Diabetic foot ulcer

 • Signature vascular impairment as a result of diabetes
• Small problem can manifest because of inappropriate blood
supply.

• Don’t 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)
Don’t remember