Introduction

Insulin is a hormone produced in the pancreas by the islets of Langerhans that allows
your body to use sugar (glucose) from carbohydrates in the food that you eat for energy
or to store glucose for future use. Insulin helps keeps your blood sugar level from
getting too high (hyperglycemia) or too low (hypoglycemia).

The cells in your body need sugar for energy. However, sugar cannot go into most of
your cells directly. After you eat food and your blood sugar level rises, cells in
your pancreas (known as beta cells) are signaled to release insulin into your
bloodstream. Insulin then attaches to and signals cells to absorb sugar from the
bloodstream. Insulin is often described as a “key,” which unlocks the cell to allow sugar
to enter the cell and be used for energy.

If you have more sugar in your body than it needs, insulin helps store the sugar in your
liver and releases it when your blood sugar level is low or if you need more sugar, such
as in between meals or during physical activity. Therefore, insulin helps balance out
blood sugar levels and keeps them in a normal range. As blood sugar levels rise, the
pancreas secretes more insulin.

If your body does not produce enough insulin or your cells are resistant to the effects of
insulin, you may develop hyperglycemia (high blood sugar), which can cause long-term
complications if the blood sugar levels stay elevated for long periods of time.

3 types of insulin

1. Animal insulin was the first type of insulin to be administered to humans to control diabetes.
Animal insulin is derived from cows and pigs.
2. Analogue insulin is a sub-group of human insulin. Analogue insulin is laboratory grown but
genetically altered to create either a more rapid acting or more uniformly acting form of the
insulin.

3. Human insulin- is the name which describes synthetic insulin which is laboratory grown to
mimic the insulin in humans.

Human insulin was developed through the 1960s and 1970s and approved for pharmaceutical
use in 1982.

Before human insulin was developed animal insulin, usually a purified form of porcine (pork)
insulin, was used.

What types of human insulin are available?

Human insulin is available in two forms, a short acting (regular) form and an intermediate acting
(NPH) form.
 NPH (Neutral Protamine Hagedorn) insulin, also known as isophane insulin, is a suspension
meaning that the insulin vial should be rolled or repeatedly turned upside down to ensure the
solution is uniformly cloudy.

Some examples of human insulin:

 Regular (short acting
 NPH (intermediate acting
 Premixed human insulins

History of Insulin
The discovery and advancement of insulin as a diabetes treatment can be traced back to the 19th
century.

Research into the development of insulin has driven scientists to take significant steps towards
understanding human biology and a number of Nobel Prizes have been awarded for research into
the hormone.

 1869

Paul Langerhans, a medical student in Berlin, discovers a distinct collection of cells within the
pancreas. These cells would later be called the Islets of Langerhans.

 1889

Oscar Minkowski and Joseph von Mering remove a dog's pancreas to study the effects on digestion.
Flies are found to be feeding off the dog’s urine, which is shown to contain sugar.

 1901

Eugene Opie discovers that the Islets of Langerhans produce insulin and that the destruction of
these cells resulted in diabetes

 1916
Romanian professor Nicolae Paulescu develops an extract of the pancreas and shows that it lowers
blood sugar in diabetic dogs. World War I prevents the experiments from continuing and it is not until
1921 that Paulescu publishes evidence of the experiments.

 1921
Dr Frederick Banting and medical student Charles Best perform experiments on the pancreases of
dogs in Toronto, Canada. Professor John Macleod provides Banting and Best with a laboratory to
carry out the experiments.
 When the pancreases are removed the dogs showed symptoms of diabetes. The pancreas was then
sliced and ground up into an injectable extract. This is injected a few times a day which helped the
dogs to regain health.

Given the early success, Macleod wants to see more evidence that the procedure worked and
provides pancreases from cows to make the extract which is named ‘insulin’.

Bertram Collip, a biochemist, joins the research team to provide help with purifying the insulin to be
used for testing on humans. Banting and Best clearly had confidence in the insulin as they were the
first humans to test the insulin by injecting themselves with it which caused them to experience
weakness and dizziness, signs of hypoglycemia.

After the group had experimented enough to gain an understanding of the required doses and how
best to treat hypoglycemia, their insulin is deemed ready to be tried on patients.

 1922
A 14-year-old boy with type 1 diabetes called Leonard Thompson is given the first medical
administration of insulin. A second dose purified by James B. Collip is successful. Leonard lives for
another 13 years. Previously patients with type 1 diabetes would be put onto starvation diets and
would have only months to live. Leonard lives another 13 years before succumbing to pneumonia.
As news of insulin’s success spread, Banting and Best begin receiving letters asking for help for
others with type 1 diabetes. Banting and Best improve their techniques for the production of insulin
and Eli Lilly becomes the first insulin manufacturer.

 1923
Banting and Macleod are awarded the Nobel Prize in Physiology or Medicine. Banting and Macleod,
however, feel Best and Collip were equally eligible and shared their prize money with their two
colleagues.

 1936
Danish physician Hans Christian Hagedorn discovers the action of insulin can be prolonged with the
addition of protamine.

 1950
NPH, an intermediate acting insulin, is marketed by Danish pharmaceutical company Novo Nordisk.

 1955
Insulin is sequenced by British biochemist Frederick Sanger, and is the first protein to be fully
sequenced. In 1958 Sanger receives the Nobel Prize in Chemistry for his research.

 1963
Insulin becomes the first human protein to be chemically synthesised.
 1978
Biotechnology firm Genentech uses recombinant DNA techniques to produce synthetic “human”
insulin. Insulin is the first human protein by to be manufactured through biotechnology.

 1982
Synthetic insulin is renamed ‘human insulin’ marking it as distinct from insulin derived from animals.
Human insulin has the advantage of being less likely to allergic reactions than animal insulin.
Humulin, manufactured by Eli Lilly, becomes widely available through the 1980s.

 1985
Novo Nordisk introduces the Insulin Pen delivery system.

 1992
Medtronic releases the MiniMed 506 insulin pump, which delivers meal bolus memory and daily
insulin totals.

 1996
Eli Lilly markets the analogue insulin lispro under the trade name Humalog. Analogue insulin is a
genetically modified form of insulin whereby the amino acid sequence is altered to change how the
insulin is absorbed, distributed, metabolised and excreted.

 2000
More than 470 patients with type 1 diabetes receive islet cell transplantation during the next five
years. The procedures help diabetes patients become free from insulin providing they take
immunosuppressant drugs.

 2013
The University of Cambridge develops an artificial pancreas that pairs the technology of an insulin
pump with a continuous glucose monitor.

 2015
Dr Edward Damiano introduces the iLet, which he calls “a bridge to a cure”. The device is a bionic
pancreas that delivers both insulin and glucagon every five minutes as required.
How is human insulin produced?
Human insulin is laboratory created by growing insulin proteins within E-coli bacteria (Escherichia
coli).

PROCESS

Recombinant DNA is a technology scientists developed that made it possible to insert a

human gene into the genetic material of a common bacterium. This “recombinant” micro-
organism could now produce the protein encoded by the human gene.

Scientists build the human insulin gene in the laboratory. Then they remove a loop of
bacterial DNA known as a plasmid and…
insert the human insulin gene into the plasmid.
Researchers return the plasmid to the bacteria and…

put the “recombinant” bacteria in large fermentation tanks.

There, the recombinant bacteria use the gene to begin producing human insulin.
Scientists harvest the insulin from the bacteria and…

purify the substance for use as a medicine for people.

Any human subjects involved?

Natural human insulin can be extracted, crystallized, and purified from

cadaverous human pancreas tissue as it is from beef pancreas and pig
pancreas. No one does this, as the few human pancreases available are far to
needed for pancreas transplantation, islet cell transplantation, and other
research for curing diabetes. Such insulin would likely cost well over $5,000
per vial (it would require well over 3 cadavers per vial) and there would be
almost no supply, perhaps enough for 10 diabetics in the world. It would be no
better than any other "human" insulin and it would be subject to most, if not
all, of the problems that we know exist for many of us with the semi-synthetic,
synthetic, and natural animal insulins.

Beneficiaries
Diabetic persons/ people who have diabetis (type 1 and 2)

Consequences

Humulin 70-30 (70% human insulin isophane suspension and 30% human insulin) is a
man-made form of a hormone that is produced in the body used to treat diabetes. The
most common side effect of Humulin 70-30 is low blood sugar (hypoglycemia).
Symptoms of low blood sugar may include headache, nausea, hunger, confusion,
drowsiness, weakness, dizziness, blurred vision, fast heartbeat, sweating, tremor,
trouble concentrating, confusion, or seizure (convulsions). Other side effects of Humulin
70-30 include:

 injection site reactions (e.g., pain, redness, irritation),

 skin thickening or pits at the injection site (lipodystrophy),
 itching,
 rash,
 weight gain, and
 swelling of your hands and feet.
Somatostatin: also known as growth hormone-inhibiting hormone (GHIH) or by several other
names, is a peptide hormone that regulates the endocrine system and
affects neurotransmission and cell proliferation via interaction with G protein-coupled somatostatin
receptors and inhibition of the release of numerous secondary hormones. Somatostatin inhibits
insulin and glucagon secretion.
Somatostatin has two active forms produced by the alternative cleavage of a single preproprotein:
one consisting of 14 amino acids (shown in infobox to right), the other consisting of 28 amino
acids.[6][7]
Among the vertebrates, there exist six different somatostatin genes that have been named SS1,
SS2, SS3, SS4, SS5 and SS6.[8] Zebrafish have all six.[8] The six different genes, along with the five
different somatostatin receptors, allow somatostatin to possess a large range of functions.[9] Humans
have only one somatostatin gene, SST.

he hormone somatostatin has active 14 aa and 28 aa forms that are produced by alternate cleavage of
the single preproprotein encoded by this gene. Somatostatin is expressed throughout the body and
inhibits the release of numerous secondary hormones by binding to high-affinity G-protein-coupled
somatostatin receptors. This hormone is an important regulator of the endocrine system through its
interactions with pituitary growth hormone, thyroid stimulating hormone, and most hormones of the
gastrointestinal tract. Somatostatin also affects rates of neurotransmission in the central nervous system
and proliferation of both normal and tumorigenic cells.

In simple terms, Somatostatin is a protein made naturally in the body. It is made by:

 a gland in the brain (hypothalamus)

 the stomach
 the pancreas
 the bowel

Somatostatin does several things. It:

 slows down hormone production, including many of the gut hormones

 slows down the emptying of the stomach and bowel
 controls the release of hormones made by the pancreas, including insulin
 slows down or stops the release of growth hormones

If you have carcinoid syndrome, you might have a man made type of somatostatin as part of your
treatment. These drugs are called somatostatin analogues. The most commonly used drugs are:

 octreotide (Sandostatin)
 lanreotide (Somatuline)

Somatostatin analogues work by slowing down the production of hormones, particularly growth
hormone and serotonin. Reducing these hormones helps to control the diarrhoea and skin flushing.
They may also shrink the tumour.

Evolutionary history
Six somatostatin genes have been discovered in vertebrates. The current proposed history as to
how these six genes arose is based on the three whole-genome duplication events that took place in
vertebrate evolution along with local duplications in teleost fish. An ancestral somatostatin gene was
duplicated during the first whole-genome duplication event(1R) to create SS1 and SS2. These two
genes were duplicated during the second whole-genome duplication event (2R) to create four new
somatostatin genes:SS1, SS2, SS3, and one gene that was lost during the evolution of
vertebrates. Tetrapods retained SS1 (also known as SS-14 and SS-28) and SS2 (also known
as cortistatin) after the split in the Sarcopterygii and Actinopterygii lineage split. In teleost fish, SS1,
SS2, and SS3 were duplicated during the third whole-genome duplication event (3R) to create SS1,
SS2, SS4, SS5, and two genes that were lost during the evolution of teleost fish. SS1 and SS2 went
through local duplications to give rise to SS6 and SS3.

Beneficiaries
Some patients who struggle with excessive somatostatin levels or endocrine
tumor called a somatostatinoma

Consequences

Side effects
Somatostatin analogues do not usually cause many side effects. The main side effects are:

 loss of appetite
 feeling sick
 feeling bloated
 stomach pain
 tiredness (fatigue)
 increased diarrhoea (this is rare)
 soreness at the injection site