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6. Non-infectious
Diseases and Genetic
Engineering
Diabetes Type 1 and Stem
Cells
What Do You Know About
It?







Do you know which are the causes of diabetes
type 1? (Maria)
And of diabetes type 2? (Lola)
Do you think that grandmother would be right to
believe she is responsible for Maria’s diabetes?
What is endocrinology department concerned
in?
What do you know about insulin? What is it?
Where is it produced? Which is its function?
Do diabetes type 1 and 2 have a definitive cure?
What is Diabetes Type 1?






The pancreas has features of both
exocrine (pancreatic juice) and
endocrine glands (hormones that
regulate blood glucose level)
One of these hormones is insulin,
secreted by β cells in islets of
Langerhans
Insulin is secreted responding to a
high blood glucose level






Insulin passes into bloodstream and
provokes the entering of glucose to tissues
of muscles and liver to be put in storage as
an energetic reserve and keeps the normal
level of blood glucose between 60 and 120
mg·dL-1
If β cells do not produce insulin, or produce
an insufficient amount, blood might have an
excess of glucose that would not enter the
tissues
It is detected with a blood or urine analysis
The Glucose Curve




1-B: Maria’s mother, normal blood
glucose level and insulin
2-A: Grandma Lola, high BGL, very
little insulin
3-C: Maria, high BGL, no insulin
Data of blood glucose concentration
before and after an ingest cannot be
compared. After an ingest, insulin
makes glucose enter the cells and
return to basal values. It makes no
sense to take more pills
Non-infectious Diseases






Most of non-infectious diseases are
genetic, in the sense that genes
determine biological activity in our cells
and organ functioning
So that a disease can be shown, tens of
altered genes may have been implied: it
is about a multigenic disease
Genes operate under regulation
depending on external factors like
feeding or habits (tobacco, alcohol,
sedentary lifestyle)
GENE EXPRESSION IN PROTEINS
AND THEIR BIOLOGICAL FUNCTION
Causes of Diabetes
Type 1 and Type 2?



Childhood chronic disease
Predisposition to suffer it is inherited, but the
most frequent type has an autoimmune
origin (like rheumatoid arthritis, lupus or
multiple sclerosis): due to some genes
malfunction, immune system does not
recognize β cells from islets of Langerhans
as of its own and destroys them, as if they
were infectious microorganisms


Lola’s diabetes is type 2, adult’s diabetes.
Glycaemia (BGL) increases out of control
because cells do not recognize insulin,
although pancreas does synthesize it:
resistance to insulin



A diet poor in carbohydrates must be
gone on, but in the most serious cases
some medication must be taken or insulin
must be injected to control glycaemia
A Treatment for
Diabetes Type 1






We must supply the daily required insulin
dose
With the help of a glucometer we can daily
measure the blood glucose level from a
drop of blood
With the help of a syringe we must inject the
required insulin dose
An insulin infusion pump injects you the
required dose, but you must be connected
there all the time
A Genetic Revolution




Until recently pig’s insulin was used,
but it provoked undesirable immune
reactions, due to some little
differences with human insulin
Now biotechnology techniques or
genetic engineering are used:
recombinant DNA technology (rDNA),
techniques that are also applied to
prenatal diagnose and police inquiry






1953 : Watson and Crick show the DNA
molecular structure and open the research
in molecular genetics
1983 : Kary B. Mullis applies the technique
of the polymerase chain reaction (PCR),
what makes possible to repeat hundredths
of times a specific sequence of DNA
2004 : first publications of human genome
that includes 3000 million of nucleotide
pairs with four types of bases: A (adenine),
T (thymine), G (guanine), C (cytosine)
Recombinant Insulin






Human insulin synthesized by means of
genetic engineering techniques
Insulin is produced by genetically modified
bacteria (Escherichia coli)
The gene of human insulin is extracted from
human cells, it is cloned (it is enlarged and
copied) and introduced into the bacteria
genome, which is a usual microorganism in
our intestine
All that has become possible thanks to
restriction enzymes, molecules that cut and
stick fragments of DNA in a selective way




Genetically modified bacteria E. Coli
produce an insulin identical to the one
produced by humans, but they are GMO
(genetically modified organisms) or
transgenic organisms
Once the transgenic organisms are
obtained, one goes to an industrial
production scale: cultures of millions of
modified bacteria cells are obtained to
produce insulin. Finally you only need to
purify, isolate and collect the product:
insulin fit for treating diabetic patients
Biotechnological Industry
and Patents





NASDAQ Biotechnology Index: it is about
an exclusive index to North-American
biotechnological industries
Today a lot of medicaments are obtained
with genetic engineering techniques
Success is mainly founded in patents:
molecules discovered by recombinant
techniques can be patented, and also new
devices for medicine’s administration and
diagnose equipment




Patents mean money: every time you
buy a medicine or a diagnose
equipment, a percentage of the price is
set aside to pay the patent. So, the firm
that has made the research recovers
the investment made, at least in part
Future of biomedical research does not
only depend on the economic power
that these firms have, but also on the
resources that public administrations
set aside
TRANSGENIC ORGANISMS
The Future:
Stem Cells for Maria?




Grandma Lola’s treatment consists of
a strict diet (no sweets at all) and
some physical exercise (walking). For
the time being she needs not to inject
herself with insulin, her glycaemia can
be under control only with pills
The little girl has recovered her child ’s
vitality, but she needs synthetic insulin
Psychological Disorders
in Child Patients







Children suffering a chronic disease may
undergo some behavior disorders
The little girl must learn that she must have
her fingers pricked and her thighs, belly or
arms injected
Maybe she felt guilty and punished, hostile
with her parents and grandma, but she has
already overcome it
Her parents have spoken clearly to her and
have not overprotected her. Sharing her
illness with grandma maybe has helped
Stem Cells




Is it possible to find a future solution
for Maria?
The doctor tells her parents that now
there is a research as a therapeutic
option, but it cannot be applied yet






Embryonic stem cells are pluripotent,
say, they can be transformed in
whatever the 200 types of cells in our
organism
Chemical signals, substances, induct
them to change gene expression, so
they produce some proteins or others
and become cardiac, epithelial, retina or
β pancreatic cells
If we could only obtain in lab embryonic
stem cells without any problems of
immunologic rejection:







We could transplant pancreatic βcells to
a patient with diabetes
We could renew the harmed cardiac
muscle of a patient waiting for a heart
transplantation
We could repair the spinal cord of a
patient with a spinal cord injury because
of a road accident
Now they are only possibilities for the
future, but they are not science fiction,
because a lot of efforts and research are
devoted, but not exempt of controversy:


There are bioethical reasons : the
use of stem cells implies the use of
human embryos, although other
alternative sources for these cells are
into research



Embryonic stem cells are obtained
from a blastocyst :






Blastocyst is a very initial stage in
embryonic development (4 or 5 days
of pregnancy)
These cells would develop an embryo
until reaching the fetal stage, that is
why its use in research is controversial
One alternative are adult stem
cells . These ones are spread through
different tissues in our organism and
they are occupied in regenerating in a
natural way damaged tissues


Many public groups, universities and
firms in biomedical research compete
for obtaining promising results



The new Law for biomedical
research , from July 2007, offers a
new frame to regulate that research



There are a lot of interests at
play(patents, money, prestige) but
there is also the risk to make frauds
and present fake data
To Learn More
Web dedicat a la diabetis:
www.diabetesjuvenil.com/
 Web nord-americana de l’enciclopèdia
mèdica Medline:
www.nlm.nih.gov/medlineplus/diabetesty
pe1.html
 Pàgina web sobre patents:
www.invenia.es/invenia:universidades:p
atentes

BUENO, David. Òrgans a la carta.
Barcelona: Universitat de Barcelona, 2007
 Roslin Institute, la institució que va
aconseguir el clon animal més conegut:
l’ovella Dolly:
www.roslin.ac.uk
 National Institutes of Health (USA):
Stemcells.nih.gov/info/basics/basics4.asp
 Llei d’investigació biomèdica, juliol de
2007:
www.boe.es/g/es/bases_datos/doc.php?
coleccion=iberlex&id=2007/12945


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6 non infectiousdiseases&geneticengineering

  • 1. 6. Non-infectious Diseases and Genetic Engineering Diabetes Type 1 and Stem Cells
  • 2. What Do You Know About It?       Do you know which are the causes of diabetes type 1? (Maria) And of diabetes type 2? (Lola) Do you think that grandmother would be right to believe she is responsible for Maria’s diabetes? What is endocrinology department concerned in? What do you know about insulin? What is it? Where is it produced? Which is its function? Do diabetes type 1 and 2 have a definitive cure?
  • 3. What is Diabetes Type 1?    The pancreas has features of both exocrine (pancreatic juice) and endocrine glands (hormones that regulate blood glucose level) One of these hormones is insulin, secreted by β cells in islets of Langerhans Insulin is secreted responding to a high blood glucose level
  • 4.
  • 5.    Insulin passes into bloodstream and provokes the entering of glucose to tissues of muscles and liver to be put in storage as an energetic reserve and keeps the normal level of blood glucose between 60 and 120 mg·dL-1 If β cells do not produce insulin, or produce an insufficient amount, blood might have an excess of glucose that would not enter the tissues It is detected with a blood or urine analysis
  • 6.
  • 8.   1-B: Maria’s mother, normal blood glucose level and insulin 2-A: Grandma Lola, high BGL, very little insulin 3-C: Maria, high BGL, no insulin Data of blood glucose concentration before and after an ingest cannot be compared. After an ingest, insulin makes glucose enter the cells and return to basal values. It makes no sense to take more pills
  • 9. Non-infectious Diseases    Most of non-infectious diseases are genetic, in the sense that genes determine biological activity in our cells and organ functioning So that a disease can be shown, tens of altered genes may have been implied: it is about a multigenic disease Genes operate under regulation depending on external factors like feeding or habits (tobacco, alcohol, sedentary lifestyle)
  • 10. GENE EXPRESSION IN PROTEINS AND THEIR BIOLOGICAL FUNCTION
  • 11. Causes of Diabetes Type 1 and Type 2?   Childhood chronic disease Predisposition to suffer it is inherited, but the most frequent type has an autoimmune origin (like rheumatoid arthritis, lupus or multiple sclerosis): due to some genes malfunction, immune system does not recognize β cells from islets of Langerhans as of its own and destroys them, as if they were infectious microorganisms
  • 12.
  • 13.  Lola’s diabetes is type 2, adult’s diabetes. Glycaemia (BGL) increases out of control because cells do not recognize insulin, although pancreas does synthesize it: resistance to insulin  A diet poor in carbohydrates must be gone on, but in the most serious cases some medication must be taken or insulin must be injected to control glycaemia
  • 14.
  • 15. A Treatment for Diabetes Type 1     We must supply the daily required insulin dose With the help of a glucometer we can daily measure the blood glucose level from a drop of blood With the help of a syringe we must inject the required insulin dose An insulin infusion pump injects you the required dose, but you must be connected there all the time
  • 16.
  • 17. A Genetic Revolution   Until recently pig’s insulin was used, but it provoked undesirable immune reactions, due to some little differences with human insulin Now biotechnology techniques or genetic engineering are used: recombinant DNA technology (rDNA), techniques that are also applied to prenatal diagnose and police inquiry
  • 18.
  • 19.    1953 : Watson and Crick show the DNA molecular structure and open the research in molecular genetics 1983 : Kary B. Mullis applies the technique of the polymerase chain reaction (PCR), what makes possible to repeat hundredths of times a specific sequence of DNA 2004 : first publications of human genome that includes 3000 million of nucleotide pairs with four types of bases: A (adenine), T (thymine), G (guanine), C (cytosine)
  • 20. Recombinant Insulin     Human insulin synthesized by means of genetic engineering techniques Insulin is produced by genetically modified bacteria (Escherichia coli) The gene of human insulin is extracted from human cells, it is cloned (it is enlarged and copied) and introduced into the bacteria genome, which is a usual microorganism in our intestine All that has become possible thanks to restriction enzymes, molecules that cut and stick fragments of DNA in a selective way
  • 21.
  • 22.   Genetically modified bacteria E. Coli produce an insulin identical to the one produced by humans, but they are GMO (genetically modified organisms) or transgenic organisms Once the transgenic organisms are obtained, one goes to an industrial production scale: cultures of millions of modified bacteria cells are obtained to produce insulin. Finally you only need to purify, isolate and collect the product: insulin fit for treating diabetic patients
  • 23. Biotechnological Industry and Patents    NASDAQ Biotechnology Index: it is about an exclusive index to North-American biotechnological industries Today a lot of medicaments are obtained with genetic engineering techniques Success is mainly founded in patents: molecules discovered by recombinant techniques can be patented, and also new devices for medicine’s administration and diagnose equipment
  • 24.   Patents mean money: every time you buy a medicine or a diagnose equipment, a percentage of the price is set aside to pay the patent. So, the firm that has made the research recovers the investment made, at least in part Future of biomedical research does not only depend on the economic power that these firms have, but also on the resources that public administrations set aside
  • 26. The Future: Stem Cells for Maria?   Grandma Lola’s treatment consists of a strict diet (no sweets at all) and some physical exercise (walking). For the time being she needs not to inject herself with insulin, her glycaemia can be under control only with pills The little girl has recovered her child ’s vitality, but she needs synthetic insulin
  • 27. Psychological Disorders in Child Patients     Children suffering a chronic disease may undergo some behavior disorders The little girl must learn that she must have her fingers pricked and her thighs, belly or arms injected Maybe she felt guilty and punished, hostile with her parents and grandma, but she has already overcome it Her parents have spoken clearly to her and have not overprotected her. Sharing her illness with grandma maybe has helped
  • 28. Stem Cells   Is it possible to find a future solution for Maria? The doctor tells her parents that now there is a research as a therapeutic option, but it cannot be applied yet
  • 29.
  • 30.    Embryonic stem cells are pluripotent, say, they can be transformed in whatever the 200 types of cells in our organism Chemical signals, substances, induct them to change gene expression, so they produce some proteins or others and become cardiac, epithelial, retina or β pancreatic cells If we could only obtain in lab embryonic stem cells without any problems of immunologic rejection:
  • 31.     We could transplant pancreatic βcells to a patient with diabetes We could renew the harmed cardiac muscle of a patient waiting for a heart transplantation We could repair the spinal cord of a patient with a spinal cord injury because of a road accident Now they are only possibilities for the future, but they are not science fiction, because a lot of efforts and research are devoted, but not exempt of controversy:
  • 32.  There are bioethical reasons : the use of stem cells implies the use of human embryos, although other alternative sources for these cells are into research  Embryonic stem cells are obtained from a blastocyst :
  • 33.
  • 34.    Blastocyst is a very initial stage in embryonic development (4 or 5 days of pregnancy) These cells would develop an embryo until reaching the fetal stage, that is why its use in research is controversial One alternative are adult stem cells . These ones are spread through different tissues in our organism and they are occupied in regenerating in a natural way damaged tissues
  • 35.  Many public groups, universities and firms in biomedical research compete for obtaining promising results  The new Law for biomedical research , from July 2007, offers a new frame to regulate that research  There are a lot of interests at play(patents, money, prestige) but there is also the risk to make frauds and present fake data
  • 36. To Learn More Web dedicat a la diabetis: www.diabetesjuvenil.com/  Web nord-americana de l’enciclopèdia mèdica Medline: www.nlm.nih.gov/medlineplus/diabetesty pe1.html  Pàgina web sobre patents: www.invenia.es/invenia:universidades:p atentes 
  • 37. BUENO, David. Òrgans a la carta. Barcelona: Universitat de Barcelona, 2007  Roslin Institute, la institució que va aconseguir el clon animal més conegut: l’ovella Dolly: www.roslin.ac.uk  National Institutes of Health (USA): Stemcells.nih.gov/info/basics/basics4.asp  Llei d’investigació biomèdica, juliol de 2007: www.boe.es/g/es/bases_datos/doc.php? coleccion=iberlex&id=2007/12945 