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- Diabetes FAQs
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- Why should
I care about diabetes?
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- Diabetes mellitus
remains the third leading cause of death in the USA after heart
disease and cancer! Most families are impacted by this disease
either through a family member, or by a friend of the family.
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- Why is diabetes
fatal if untreated?
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- In
this disease, the levels of glucose in the blood are not controlled
adequately. In particular, glucose levels become elevated from
normal concentrations, leading to the excretion of this key energy
source in the urine. More importantly, cells cannot make use
of the increased amounts of glucose in the blood, and so energy
generation pathways cannot operate properly. As glucose is the
only energy source that can be used by nerve cells, brain function
is severely impaired. The lack of glucose within the cells then
leads to increased metabolism of fatty acids and the molecules
that are used to make cell membranes, resulting in the formation
of "ketone bodies" which decrease the acidity of the
blood. In turn, the kidney excretes the excess acid but in so
doing, essential minerals like sodium, potassium and phosphate
ions are also lost from the body. Excretion of these materials
requires large volumes of water and, for this and a number of
other reasons, the blood volume becomes severely decreased even
if the diabetic drinks large quantities of water. This raises
the blood pressure, because the blood becomes very viscous (especially
as there is so much glucose present), straining the heart and
also damaging the kidneys.
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- What is insulin
and where does it come from?
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- How
does insulin control the levels of glucose in the blood? The
release of insulin into the bloodstream leads to a reduction
in the levels of circulating glucose through a number of pathways.
First, insulin activates the proteins that actively transport
glucose from the blood into the interior of cells where is can
be used as a source of energy. In addition, insulin also stimulates
liver cells to convert glucose into glycogen.
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- What are
the Islets of Langerhans?
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- These
are small groups of cells that are found in the pancreas and
which release various hormones directly into the blood. The islets
of Langerhans only comprise about 1-2% of the total number of
cells in the pancreas, the main function of this organ being
to release digestive enzymes into the intestine. There are three
types of cells in the islets of Langerhans, each synthesizing
a different molecule that regulates the balance of energy metabolism
in the body. A-cells secrete glucagon, a polypeptide
made of 29 amino acids, into the blood. Glucagon has the opposite
effects to insulin, in that it causes glycogen to be broken down
into glucose by the liver, and it stimulates adipose tissue to
release fatty acids. b-cells secrete insulin
into the blood in response to high levels of glucose. D-cells
secrete a small peptide called somatostatin. This peptide inhibits
insulin release and glucagon from the a and b-cells of the pancreas.
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- What is glycogen?
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- Glucose
is stored in cells in the form of a complex polymer called glycogen.
This molecule is very similar in structure to starch except that
it has a large number of branches from each chain. When glucose
is available in large amounts in muscle and adipose tissues,
insulin release activates How does glucose enter cells? Glucose
molecules cannot pass directly through cell membranes. Their
entry is effected by the presence of proteins that create holes
by spanning the membrane. These proteins are called glucose transporters,
and five different forms have been characterized, each with slightly
different properties and distribution throughout the tissues.
For example, GLUT2 is found in the b-cells of the pancreas
and in liver cells. Insulin does not appear to affect the ability
of GLUT2 to transport glucose. Muscle and fat cells, on the other
hand, possess the GLUT4 transporter which is stimulated by insulin
so that more glucose is taken up by these cells when blood insulin
levels are high. Red blood cells contain large amounts of the
GLUT1 glucose transporter, the structure of which appears to
consist of twelve cylinders that pass through the membrane and
which are arranged in a circle to create a pore.
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- What is the
difference between Type 1 and Type 2 diabetes mellitus?
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- Type
1 diabetes often strikes suddenly in early childhood and results
from the destruction of the b-cells in the pancreas.
These cells synthesize and secret insulin into the blood where
it can exert its effects. Current evidence suggests that it takes
several years for the immune system to attack the pancreatic
b-cells, and diabetes results when approximately
80% of them are destroyed. Type 2 diabetes mellitus usually occurs
for reasons of diet in individuals with a genetic predisposition
for this genetic condition. In this disease, the pancreas secretes
normal levels of insulin into the blood, but there appears to
be a lack of insulin receptors on liver cells. Hence, removal
of glucose form the blood through glycogen synthesis does not
take place. Equally, cells are not stimualte to transport glucose
from the blood. The exact pathway of this regulation of insulin
receptor levels seems unclear at present.
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- What is known
about the insulin receptor?
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various reasons, it is believed that the insulin has an insulin-binding
domain which is on the outside of a cell that is connected to
a domain by a polypeptide segment that is bound within the cell
membrane. In common with many other protein hormone receptors,
the two molecules of the insulin receptor are brought together
by one insulin molecule. When the receptor assumes a dimeric
form, then the intracellular domain can act to catalyze the phosphorylation
of various proteins in the cell, using the breakdown of ATP as
an energy source. This event then leads to activation of the
cell systems that allow glucose to be transported from the blood
into the cell, where the sugar is either broken down to release
energy or used to form glycogen, a polymer of glucose that acts
as an energy store.
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- What is the
structure of insulin?
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- Insulin
is a very complex protein that is made from two polypeptide chains.
It has been crystallized and so the three-dimensional structure
is known at the molecular level. Unfortunately, insulin has a
tendency to form complex structures involving six individual
insulin molecules when it forms crystals. As single molecules
of insulin are biologically active, it is hard to be sure of
the structural form of insulin that binds to its receptor. However,
by using techniques to engineer the amino acid sequence of proteins,
a mutant form of insulin has been produced that does not form
complex oligomeric structures when it crystallizes. Such information
can be used as part of efforts to discover new molecules that
can bind to the insulin receptor and act in a similar way to
the protein hormone. Such compounds might be used as drugs in
place of insulin, especially if they could be taken by mouth
rather than by injection.
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- Why does
the breath of an untreated diabetic smell of acetone (nail varnish
remover)?
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- When
fatty acids are broken down to form acetyl-CoA, a key compound
in the generation of energy from oxygen, a side-reaction occurs
in liver mitochondria that leads to the formation of acetoacetate.
In turn, acetoacetate can undergo a variety of reactions. One
of these involves the breakdown of acetoacetate to give carbon
dioxide and acetone. Acetone cannot be used by the cell and therefore
builds up in the blood. As acetone is relatively volatile, some
of this compound is expelled from the lungs in the breath of
the diabetic.
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- Do injections
of insulin really cure Type 1 diabetes mellitus?
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- Daily
injections of insulin act to replace that which would have been
formed in the pancreas. The schedule of insulin injections cannot
often be precisely timed to the metabolic needs of the individual,
and so the lifespan of most diabetics are reduced by a number
of complications such as kidney failure, nerve impairment and
cardiovascular disease. But although diabetics can live a relatively
normal life by taking insulin, watching their diet and following
precise exercise schedules, a real cure would be to prevent an
autonomic attack (Type 1 Diabetes), replace the lost b-cells
and prevent their subsequent destruction by the immune system.
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- How is Ixion
developing a cure for Type 1 diabetes mellitus?
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- Scientists
at Ixion have developed conditions for growing the pancreatic
islets in the laboratory. Cell culture for use in islet replacement
therepy. Ixion's products are presently in research phase.
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