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ANIMAL MODELS OF
DIABETES
PRESENTED BY:
Ashutosh B Mahale
M.Pharm (Pharmacology)
Diabetes is diagnosed when a person has
too much glucose (sugar) in the blood.
This happens because the pancreas cannot
make enough insulin.
Insulin is produced in the pancreas and has two
jobs in the body - the first is to transport glucose
from the blood supply into fat and muscle cells,
where it can be used for energy. The second is to
switch off the liver once the level of glucose in
the blood is high enough. Diabetes is the result
of the body not creating enough insulin to keep
blood glucose levels in the normal range.
45
08:43
IDDM
3
Chemical Induced
Insulin induced
Virus induced
Surgically induced
Combination
Genetic induced
08:43
NIDDM
4
Chemical Induced
Genetic models
Hybrid cross
Transgenic
Unknown
hereditary and
environmental
conditions
08:43
IDDM Chemical
5
i) Alloxan induced Diabetes
ii) Streptozocin induced Diabetes
08:43
6
(1) Alloxan induced diabetes:-
Purpose –
Induction of diabetes using chemical alloxan.
In most species, triphasic time course is observed.
(Initial rise of glucose is followed by decrease, again
followed by sustain increase of blood glucose).
08:43
7
08:43
8
Procedure
Animal
3 Group are selected as (control, standard, test )
Rabbits Rats Beagle dogs
Weight 2.0-3.5 kg 150-200 gm 15-20 kg
Route
of
alloxan
Dose
Ear vein subcutaneously Intravenously
150 mg/kg 100-175 mg/kg 60 mg/kg
08:43
9
Evaluation
Blood glucose level is estimated
Compare the result of test with standard and control.
08:43
10
Drawbacks
High mortality
Ketosis
Diabetes induced is reversible
Cannot be done on guniea pigs
08:43
11
2) Streptozocin induced diabetes
Purpose:
Induction of diabetogenic activity of antibiotic
streptozocin.
 Triphasic response seen.
08:43
12
Mechanism
Cell methylation
Free radical generation
Nitric oxide production
08:43
13
Procedure
Male Wistar Rat- 150-200 gm
Group- Test, Standard, Control
STZ. Dose- 60 mg/kg iv or ip
Done in mice (175-200 mg/kg i.p. or i.v.) and dogs
(15 mg/kg for 3 days)
08:43
14
Evaluation
Blood glucose level is estimated.
Compare the result of test with standard and control.
08:43
15
ADVANTAGE
• Selectivity towards β cells
• Lower mortality rate
• Longer diabetes induction
Limitations
• Rabbits and guniea pigs are resistant to its
diabetogenic effect
08:43
Insulin antibodies induced
16
08:43
Viral induced
17
Principle
D-variant of Encephalomyocarditis virus (EMC-D)
selectively infects and destroys pancreatic β-cell.
elevation of islet cell antibody, and prolonged
presence of viral RNA in the pancreas.
Associated with chronic islet cell inflammation,
Others: RNA picornavirus, Coxsackie virus
08:43
Surgical induced
18
Partial pancreatectomy: usually anterior lobe is left
intact
Disadvantages
Loss of α cells (glucagon and somatostatin loss)
Loss of pancreatic enzymes (creates digestive
problems)
Difficult to achieve
08:43
Combination
Surgical+Chemical:
19
in cats and dogs
Genetic
• BB rat
• NOD mouse
08:43
BB Rat
A model of spontaneous diabetes
associated with insulin deficiency due
to autoimmune destruction of β cells
Bio Breeding
rat
20 08:43
NOD Mice
•Develop diabetes
between 100 and 200
days of age.
Non-Obese Diabetic
mice
•As well as rapid weight
loss, polyuria, and
severe glucosuria.
• Caused by specific T-
cell mediated
destruction of β cells
21 2108:43
NIDDM
i)
Chemical
22
Neonatal streptozocin model
 Species: Rats (Wistar or Sprague-Dawley)
 Effect: Initial rise in plasma glucose and becomes
normoglycemic by 3 weeks of age
 Others: Adrenaline in rabbits
08:43
23
Procedure:
STZ (80-100mg/kg/i.p.) given at birth or within 5
days
Severe β cell destruction
Reduction in insulin stores and raised glucose levels
β cells of neonates partially regenerate (in contrast to
adult rats)
08:43
Transgenic techniques
A transgenic animal is one that carries a foreign gene that
has been deliberately inserted into its genome.
takes place.
Transgenesis is the process by which mixing up of genes
 Foreign genes are inserted into the germ line of the
animal, so it can be transmitted to the progeny.
Use : for creating animal models of diabetes
08:43
25
Transgene made of 3 parts:



Promoter
Gene to be expressed
Termination sequence
Introduction of foreign gene into the animal
 Embryonic stem cell method
 Pronuclear microinjection method
08:43
08:43
08:43

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in vivo antidiabetic model