Download Lecture 9 - Dentistry 09

Lecture 9
20\2\2011-02-20
We talked in the last lecture about langerhans islets, these cells alpha beta
delta and ".." .. of course there is four or five hormones produced but the
most important are insulin and glucagon.
Insulin
2 chains : α chain and β chain
-α chain is inactive
- β chain is the active part
- But the 2 chains have to be connected to each other with disulfide
bridges.
- Also there's a bridge in the A chain.
- It has a short half life = 6 minutes.
You remember we said that 6 hormones affect the glucose metabolism:
Two for short term regulation
1.Insulin
2.glucagon
Other four for long term regulation:
3.catecholamines (adrenaline)
4.cortisol
5.grwoth hormone
6.thyroid hormones
There is one hormone hypoglycemic hormone in the body : Insulin, it
decreases blood glucose level.
The others are hyperglycemic. The most potent hyperglycemic hormone
is the Glucagon.
Glucagon, Epinephrine, Cortisol, growth hormone all these increase
blood glucose level by different processes:
1. Glycogenlysis  glucagon and epinephrine
2. Gluconeogenesis  all of them, but most potent: Cortisol.
3. Lipolysis  epinephrine, cortisol and growth hormone.
Inhibition of glucose uptake just 2 hormones: Cortisol and Growth
hormone.
______
The receptor of Insulin is an "Enzyme-linked receptor" . The enzyme
Tyrosine kinase is linked to the receptor. The receptor is composed of 4
subunits: 2 alpha and 2 beta.
Mechanism of insulin:
1. Insulin binds with alpha, and beta is activated
2. The enzyme is activated.
3. Formation of second messenger.
4. Then, the second messenger activate entry of glucose, which means it
activates the glucose transporters.
Insulin plays role in glucose transport as we said, protein synthesis, fat
and growth.
This is (on the slide) the activation of glucose transporters through
activation of tyrosine kinase receptors:
You see here glucose transporter type 4, sometimes type 2, because there
are many types of glucose transporters.
Insulin may produce 2 second messengers : IP3 and DAG. To increase
amino acid entry into cells and also electrolytes: Na+ , K+ …
*Insulin like growth factor, why do we call it insulin like growth factor?
Because it has similar receptors as insulin. And also there is similarity in
the structure but not exact.
There are many stimulators of Insulin:
1.Increased glucose concentration
2.Increased amino acid
3.Increased free fatty acid
4.glucagon, cortisol, growth hormone
5.Obesity
Etc.. (written on the slide)
Inhibitory factors:
1.Decreased blood glucose
2.fasting
3.Exercise
4.somatostatin
5.leptin : hormone secreted by fat cells.
Etc.. in the slide
The most important stimulating factor is Glucose but it has to be
metabolized to stimulate the insulin.
Glucose (metabolized) ATP increases  ATP channel closed
depolarization Ca++ entry  then Insulin secretion.
*The most important is the entry of Calcium.
*Some other stimulators, stimulate insulin secretion but not in this way,
by producing 2 second messengers or cAMP. But the main way is entry
of Calcium.
_______
You remember, Fat obese person with non-insulin dependant diabetes
mellitus, he need too much insulin as to produce normal function. You
can see on the figure in the slide the difference in need of insulin between
control and diabetic patient, diabetic patient needs too much insulin
because of low number of receptors and low affinity.
Glucose levels:( this figure can be found page 969 in guyton book ed.11 )
Fasting level = 100mg/ml plasma
Below 50mg/ml plasma  no insulin secreted
The maximum level  between 300 and 400 mg/ml plasma
Above 400mg/ml plasma  no increase in insulin secretion
You see this experimental animal (in the slides) is injected by glucose,
immediately insulin increases then after minutes it decreases, it retains to
normal level. Who can explain this? ( figure in page 968 in guyton )
- Glucose injected stimulates the present insulin in the granules.(not
stored, storage is only in thyroid)
- Release from the granules  insulin increases
- depletion occurs  decreases
- after minutes, new insulin is synthesized  normal level
_______
In insulin deficiency:
-All food components are affected; Glucose, Lipids, Proteins.
-Acetic acid increases
-Fatty acid increases
-Blood glucose increases
-catabolism of protein increases
Insulin affects: Adipose tissue, Muscle cells, Liver, and general increase
in cell growth
*The most important organ in homeostasis of glucose: Liver.
Insulin facilitates the entry of glucose in almost all cells of the body
except four:
1. Brain
2. Kidneys tubules
3. Intestinal mucosa
4. RBCs
These they take glucose spontaneously.
Insulin normalizes glucose level, which is normally 100mg/ml
Brain takes glucose spontaneously while others need insulin for entry of
glucose,
Muscles and other tissue : 30-40%
Liver: 5% ….Liver takes glucose and also releases glucose for storage.
It's a multi-functional organ!
_____
There's no glucose in urine when concentration of glucose is below 180
mg/dl .
This is the renal threshold for the glucose.
Hyperglycemia concentration of glucose : 300mg/dl
Diabetes mellitus occurs! Glycosuria occurs! Why? Because glucose is
too much above 180 !
*Glycosuria: appearance of glucose in urine.
Glucose entry into cells affected
Muscles and other cells affected
Glucose coming from the liver is more than going to the liver
Because there's too much metabolism of glucose there's too much
amino acids and fatty acids going to the liver and also Lactic acid.
_______
When the body depends almost entirely on fat cells, the level of ketone
bodies increases.
Ketone bodies are hydroxybutyric acid, acetone , and acetoacetic acid.
These produce acidosis along with dehydration and coma.
Causes of acidosis and dehydration:
-When the body depends almost entirely on fat for energy, ketone bodies
concentration increases and causes the enzyme " hormone -sensitive
Lipase" in the fat cells to become strongly activated when insulin
deficiency is present.
-When keto acids are excreted, they are replaced by Hydrogen.
- Third reason is going to be mentioned below in bold letters.
These occur in diabetic patient :
-decrease glucose uptake  result: Hyperglycemia + Glycosuria +
osmotic diuresis
*osmotic diuresis: glucose concentration increases in the nephron causing
the osmotic pressure to rise so the water is not reabsorbed properly
because of the high osmotic pressure in the filtrate. So too much water is
execreted, dragging with it electrolytes.
Third reason: When potassium is excreted, it is replaced by hydrogen
ions.
*Increased protein catabolism: there's no glucose available for cells for
energy. Fat is first utilized, causing disturbance in cells, then there protein
catabolism occurs, because the cells don’t know how to deal with this
deficiency of glucose.
There is disturbance, some cells prefer fatty acids, others prefer amino
acids, this depends on the type of cells.
There is problem in the metabolism of carbohydarates, lipids, as well as
proteins.
*Lipolysis: Increased plasma free fatty acids  increased ketone bodies
Ketogenesis
Ketourea : excreted in urine
Ketonemia: ketone bodies in blood
Acidosis, coma and death!
*Just to know: Coma also occurs in Hypoglycemia.
The diabetic patients always take insulin, because sometimes in these
patients hypoglycemia occurs, if they don't take insulin, they go into
Coma.
Below 50mg/dl glucose coma may occur ( depends on the person too)
sometimes below 30.
How do you differentiate between a diabetic person and hypoglycemic
person in coma?
By urine sample or a more convenient and obvious way: smell his breath,
if it smells like alcohol it means he is diabetic of type 1 ( lack of insulin
production by type β.
We have two type of diabetes mellitus:
1.Insulin dependant diabetes mellitus
2.juvenile diabetes mellitus: usually genetic, usually appears in children,
insulin is low or absent, therapy is insulin.
Type 2 diabetes mellitus maybe genetic also.
Non insulin dependant diabetes mellitus,
maturity-onset diabetes mellitus,
obesity diabetes mellitus: usually in old obese individual, it may occur in
young obese.
Insulin normal or high. Problem is in the receptors. Therapy is tablets that
stimulate secretion of insulin. In severe cases; chronic and acute, insulin
therapy.
I read in the book that diabetes mellitus is divided in to :
1- type I( insulin- dependent diabetes mellitus ) caused by lack of insulin secretion .and the
usual on set of type I occurs at about 14 years of age so its often called "juvenile diabetes
mellitus "
2- type II (non-insulin –dependent diabetes mellitus ) caused by decreased sensitivity of target
tissues to the metabolic effect of insulin . and in most cases the on set of type II occurs after age
of 30 between ages 50 and 60 and it happen gradually so it is often referred to as " maturity
onset diabetes "
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Done by: Amani Khasawneh 