INSULIN

MERT AYGÜLER

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•Insulin is a hormone that is central to
regulating fat and steroids 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
muscle.
•Insulin is produced in the islets of
Langerhans in the pancreas.
PROTEIN STRUCTURE
The hexamer-monomer conversion is one of the central aspects
of insulin formulations for injection. The hexamer is far more
stable than the monomer, which is desirable for practical
reasons, however the monomer is a much faster reacting drug
because diffusion rate is inversely related to particle size.

Insulin is produced and stored in the body as a

hexamer while the active form is the monomer.
 Insulin is produced in the pancreas and released when any of
SYNTHESIS OF INSULIN

the several stimuli are detected.

The stimuli include ingested protein and glucose in the blood
produced from digested food.
If the carbohydrate includes glucose then that glucose will be
absorbed into the bloodstream and blood glucose level will
begin to rise.
In target cells, insulin initiates a signal transduction, which has
the effect of increasing glucose uptake and storage.
Finally, insulin is degraded, terminating the response.
EFFECTS OF INSULIN ON METABOLISM

 Inhibits protein degradation.

Increases protein synthesis especially in muscle tissue.

Inhibits the release of fatty acids.

Increases the transport and metabolism of glucose in fat cells.

Thus, lipid synthesis (lipogenesis) increases.

Increase of DNA replication and protein synthesis via control

of amino acid uptake.

Effect of insulin on glucose uptake and metabolism. Insulin binds to its
receptor (1), which in turn starts many protein activation cascades (2).
These include: translocation of Glut-4 transporter to the plasma
membrane and influx of glucose (3), glycogen synthesis (4), glycolysis
(5) and fatty acid synthesis (6).
DISEASES
When control of insulin levels fails, diabetes mellitus will
result. As a consequence, insulin is used medically to treat
some forms of diabetes mellitus .Two types of disease
which caused by insulin are type 1 and type 2 diabetes
mellitus.
Type 1 diabetes: results from the body's failure to produce
insulin, and presently requires the person to inject insulin.
Type 2 diabetes: results from insulin resistance, a condition in
which cells fail to use insulin properly, sometimes combined
with an absolute insulin deficiency.
 Type 1 diabetes (previously known as insulin-dependent), is characterized
by deficient insulin production and requires daily administration of insulin.
Symptoms include excessive excretion of urine (polyuria), thirst
(polydipsia), constant hunger, weight loss, vision changes and fatigue.
These symptoms may occur suddenly.
 Type 2 diabetes (formerly called non-insulin-dependent or adult-onset)
results from the body’s ineffective use of insulin. Type 2 diabetes comprises
90% of people with diabetes around the world, and is largely the result of
excess body weight and physical inactivity. Symptoms may be similar to
those of Type 1 diabetes, but are often less marked. As a result, the disease
may be diagnosed several years after onset, once complications have
already arisen.
 Patients with Type 1 diabetes mellitus depend on external
INSULIN THERAPY

insulin (most commonly injected subcutaneously) for their

survival because the hormone is no longer produced internally.
Patients with Type 2 diabetes mellitus are insulin resistant,
have relatively low insulin production, or both; certain patients
with Type 2 diabetes may eventually require insulin if other
medications fail to control blood glucose levels adequately.
Biosynthetic "human" insulin is now manufactured for
widespread clinical use using genetic engineering techniques
using recombinant DNA technology. actual human DNA is
inserted into a host cell .The host cells are then allowed to
grow and reproduce normally, and due to the inserted human
DNA, they produce a synthetic version of human insulin.
There are several problems with insulin as a clinical treatment for
diabetes:
Mode of administration.
Selecting the 'right' dose and timing.
Selecting an appropriate insulin preparation (typically on
'speed of onset and duration of action' grounds).
Adjusting dosage and timing to fit food intake timing,
amounts, and types.
Adjusting dosage and timing to fit exercise undertaken.
Adjusting dosage, type, and timing to fit other conditions, for
instance the increased stress of illness.
It is simply a nuisance for patients to inject whenever they eat
carbohydrate or have a high blood glucose reading
INSULIN IN A PILL
Unlike many medicines, insulin cannot be taken orally at the
present time efficiently. Like nearly all other proteins
introduced into the gastrointestinal tract, it is reduced to
fragments, whereupon all insulin activity is lost. There has
been some research into ways to protect insulin from the
digestive tract, so that it can be administered in a pill.
The scientists used the insight they gained to design a pill that
can transverse the stomach without being broken down,
facilitating the transfer of insulin across cells and into the
bloodstream.
AN ARTIFICIAL PANCREAS
Scientists are pairing to create an artificial pancreas
for people with diabetes. At its most basic level, an
artificial pancreas consists of three components: a
continuous sensor to detect glucose levels in real time, a
miniature computer that can take those readings and use
an algorithm to predict what will happen next and
determine how much insulin is necessary to keep the
levels steady, and an insulin pump driven by the
computer that doses out the appropriate amount of the
drug. However, the user must still decide how much
insulin he needs and dose it out himself. In an artificial
pancreas, specially-designed algorithms would calculate
how much insulin is required, and how quickly, and
then signal the drug’s delivery without human
intervention.
SMART INSULIN

A new drug that senses glucose levels

and delivers insulin on demand may reduce
the number of daily injections for patients
with diabetes. Smart Insulin works via
competitive binding, in which insulin
(orange lines), attached to a sugar group
(orange hexagons), binds with a sugar-
binding molecule (blue circle) in solution.
When glucose (blue hexagons) in the body
is high, it competes with insulin to bind to
the sugar-binding molecules, displacing
insulin and releasing it into the bloodstream
as needed.
REFERENCES
1. World Health Organization – Diabetes.
http://www.who.int/mediacentre/factsheets/
2. First Successful Laboratory Production of Human Insulin
Announced. News Release Genentech, 06, 1978
3. Ebey Soman, Scienceray, Regulation of Glucose by Insulin,
May 4, 2009.
4. http://www.littletree.com.au/dna.htm
5. Arlene Weintraub, Insulin in Pill, Technology Review,
Biomedicine, 05,2010
6. Lauren Gravitz, An Artificial Pancreas, Technology Review,
Biomedicine, 08,2008
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