Diabetes Gene

Therapy
Name :E.Preetham Reddy
Id Number : 2012510127

Gene Therapy
Definition : the transplantation of
normal genes into cells in place of
missing or defective ones in order to
correct genetic disorders.
Gene therapy is the use
ofDNAas a
pharmaceutical
agent to treat disease.

About the disease

Diabetes mellitus : Diabetes
mellitus(DM), also known as
simplydiabetes, is a group of metabolic
diseases in which there are highblood sugar
levels over a prolonged period .

Diabetes is due to either thepancreas

not producing enoughinsulin, or the
cellsof the body not responding properly
to the insulin produced

Types of Diabetes mellitus:

The types of Diabetes are as follows:
1.Type I DM
2.Type II DM
3.Gestational Diabetes

Diabetes mellitus type1(also known

astype1 diabetes, orT1DM;
formerlyinsulin-dependent
diabetesorjuvenile diabetes) is a form of
diabetes mellitusthat results from the
autoimmunedestruction of theinsulinproducingbeta cellsin thepancreas.

Type II
Type 2 DMbegins with
insulin resistance, a condition in
which cells fail to respond to
insulin properly. As the disease
progresses a lack of insulin may
also develop.This form was
previously referred to as "non
insulin-dependent diabetes
mellitus" (NIDDM) or "adult-

Gestational Diabetes
Gestational diabetes(orgestational
diabetes mellitus,GDM) is a condition in
which women without previously diagnosed
diabetesexhibithigh blood glucoselevels during
pregnancy(especially during their third
trimester). Gestational diabetes is caused when
insulin receptorsdo not function properly. This is
likely due to pregnancy-related factors such as
the presence ofhuman placental lactogenthat
interferes with susceptible insulin receptors.

Diabetes Genome
Genome : The haploid set of chromosomes in a
gamete or microorganism, or in each cell of a
multicellular organism.

Diabetes Genome

: The approach used by

researchers is therefore to examine lots of families
with multiple offspring affected by diabetes, using a
strategy called a genome-wide scan for linkage. By
looking at short sequences of DNA that show
inherited variations in length ('microsatellite' genetic
markers), spaced evenly throughout the genome.


The first genome-wide scan for type 1 diabetes
susceptibility regions was published in 1994; indeed,
this was the first genome scan for a common human
disease. Several more scans have been carried out
since, each obtaining extremely strong evidence for
linkage to the IDDM1 HLA region.
This 'meta-analysis' produced statistically significant
evidence of linkage for only three regions (the
previously identified IDDM1 and IDDM2, and a novel
locus on chromosome 16q22-24) and 'suggestive'
evidence for six regions (IDDM7, IDDM10, IDDM12,
IDDM13 and IDDM15, and a novel locus on
chromosome 1q42)

Targeted sequencing of genes

associated with type 2
diabetes

For type 2 diabetes, more than 70

common genetic variants have been identified
by extensive genome-wide association studies.
The coding and 5 and 3 untranslated
regions of 130 genes (1.2 megabases in total)
were sequenced in 1880 and 1840 controls.
To increase efficiency, sequencing was
done in pools (20 individuals per pool) and
library preparation for each pool was done
using the Agilent Sure Select target enrichment
method.

Micro-RNA in the regulation of

glucose
Micro RNAs
(miRNA) are
single-stranded
transcribed RNAs
of 1925
nucleotidesin
length that are
generated from
endogenous
hairpin structured
transcripts
throughout the
genome


Pancreatic islet-specificmiR-375inhibits insulin
secretion in mouse pancreatic -cells by inhibiting
the expression of the proteinmyotrophin. An
overexpression of miR-375 can completely
suppress glucose-induced insulin secretion, while
inhibition of native miR-375 will increase insulin
secretion. In another study, increasing the level of
miR-9, a different miRNA, resulted in a severe
defect in glucose-stimulated insulin release.
This happens because miR-9 down-regulated
the transcription factorOnecut2(OC2) that controls
the expression ofRab27a effector granuphilin, a
key factor in controlling insulin release

Gene therapy of diabetes:

glucose-stimulated insulin
secretion in a human hepatoma
cell line
While glucose responsiveness
commenced at a lower concentration than
normal islets, a secretion curve
approaching normal physiological
conditions was generated.
Immunoelectron microscopy
revealed the presence of insulin-containing
granules, similar in size and appearance to
those of the normal beta cell.

These

results demonstrate that while it is most likely that

the HEP G2ins/g cell line predominantly secretes insulin via
the constitutive pathway, significant acute regulated
release was seen in response to glucose, and thus
represents significant progress in the creation of a
genetically engineered 'artificial beta cell' from a human
hepatocyte cell line.


Other forms of diabetes mellitus
include congenital diabetes, which is due
togeneticdefects of insulin secretion,
cystic fibrosis-related diabetes, steroid
diabetes induced by high doses of
glucocorticoids, and several forms of
monogenic diabetes.
Mechanism of insulin release in normal
pancreatic beta cells insulin production is
more or less constant within the beta cells. Its
release is triggered by food, chiefly food
containing absorbable glucose.

symptoms

Diagnosis

Diabetes mellitus is characterized

by recurrent or persistent
hyperglycemia, and is diagnosed by
demonstrating any one of the following:

Fasting plasma glucose level 7.0mmol/l (126mg/dl)

Plasma glucose11.1mmol/l (200mg/dl) two hours
after a 75g oral glucose load as in a
glucose tolerance test
Symptoms of hyperglycemia and casual plasma
glucose 11.1mmol/l (200mg/dl)
Glycated hemoglobin(Hb A1C) 6.5%

Prevention:

There is no known preventive measure for type1

diabetes. Type2 diabetes can often be prevented by a
person being anormal body weight, physical exercise, and
following a healthy diet.Dietary changes known to be
effective in helping to prevent diabetes include a diet rich
inwhole grainsandfiber, and choosing good fats, such as
polyunsaturated fatsfound in nuts, vegetable oils, and fish .

Limiting sugary beverages and eating less

red meat and other sources ofsaturated fatcan also
help in the prevention of diabetes.Active smoking is
also associated with an increased risk of diabetes,
sosmoking cessationcan be an important preventive
measure as well.

Medications
Metforminis generally recommended as a first line
treatment for type2 diabetes, as there is good
evidence that it decreases mortality.
Routine use ofaspirin, however, has not
been found to improve outcomes in uncomplicated
diabetes.
Angiotensin converting enzyme inhibitors
(ACEIs) improve outcomes in those with DM while
the similar medicationsangiotensin
receptor blockers(ARBs) do not.

In gene therapy, the nucleic acid molecule is packaged within a "

vector", which is used to get the molecule inside cells within the body.

Thank You