in this slide, You will get to know about different screening Invivo and Invitro models used for screening of Anti-Diabetic drugs used in Pharmacology.

1. Screening Models for
Anti-Diabetic drugs
Presented by:
Shaikh Nisar Ali (M.Pharm)
Dept.of Pharmacology
Guided by:-
Dr.Nitin Mahurkar Sir.
(HOD Pharmacology)

2. Basics...
• When we eat foods like Carbs,Milk , dairy products , fruits etc. it is
broken down in the stomach and digestive system into glucose which
is a type of sugar.
• From that glucose only we get energy.
• The glucose moves into the bloodstream and the body detects that
the blood glucose level is rising.
• In response to that pancreas which is a gland starts to release an
hormone called insulin.
• Insulin helps the glucose enter into the cell and we get energy.

3. DIABETES
• Diabetes is a group of disease in which the body either doesn’t
produce insulin or body does not properly use the insulin that
is produced or a combination of both.
• When any of these things happen the body is unable to get sugar
from the blood into the cell.
• This leads to rise in blood sugar level.
• Lack of insulin or resistance to insulin causes sugar to build up in your
blood .
• This can lead to many health problems .

5. Normal Person

6. There are 4 major types of Diabetes.
1. Type 1 Diabetes.
2. Type 2 Diabetes.
3. Gestational Diabetes.
4. Pre- Diabetes.

7. 1. Type-1 Diabetes.
• It is also called as insulin dependent diabetes.
• Type 1 diabetes is believe to be an auto immune condition .
• It happens when the immune system mistakenly attack and destroy is
the Beta- cells of pancreas that produce insulin .
• The damage is permanent.
• What makes the attack is not clear. There may be both genetic and
environmental factors.
• Usually occour in childhood and adults under 40s and its about 10%
of all cases.

8. In Type-1 Diabetes.

9. 2. Type-2 Diabetes.
• It is also called as known insulin dependent diabetes.
• In type -2 diabetes the pancreas produces enough Insulin but
something goes wrong either with receptor binding or insulin
signalling inside the target cells.
• The cells were not responding to Insulin and therefore can not import
glucose.
• Tpye-2 diabetes is Insulin resistant Diabetes.
• The exact cause in unknown. Contributing factors may include lack of
excercise and being overweight. There may also be other health
factor or environmental reasons.

10. In Type-2 Diabetes.

11. 3.Gestational Diabetes.
• Gestational diabetes is due to insulin blocking hormones produced
during pregnancy
• This type of diabetes only occurs during pregnancy
• Blood sugar levels are high during pregnancy
• There is a high risk of type 2 diabetes and cardiovascular disease.

12. 4.Pre-Diabetes.
• At least 79 million people are diagnosed with pre - diabetes each year.
• It is above average blood glucose levels, not high enough to be
classified under type 1 or type 2 diabetes.
• Causes long - term damage to body, including heart and circulatory
system.
• Starts with unhealthy eating habits & inadequate exercise.

13. How common is diabetes.
• Worldwide, about 5 to 10 percent of people with diabetes have type
1, while 90 to 95 percent have type 2 diabetes.
• 86 million are thought to have pre-diabetes. But most people with
pre diabetes don't know that they have the condition.
• About 15 to 30 percent of people with pre - diabetes will develop
type 2 diabetes within five years.
• You're more likely to develop diabetes if you have a family history of
the disease.

14. General Symptoms of Diabetes.
1. Blurred vision.
2. Tiredness.
3. Weightloss.
4. Urination.
5. Thirst.
6. Genital Itching.
7. Slow healing.

15. Potential Complication.
1. Vessel disease leading to Heart Attack or stroke
2. Eye problems called retinopathy
3. Infection of skin
4. Nerve damage or neuropathy
5. Kidney damage or nephropathy
6. High Blood Pressure
7. Birth defects etc.

16. Screening Models of Antidiabetic
drugs.

17. In-Vivo Studies
• Studies in which the effects of various biological entities are
tested on whole living organisms or cells, usually animals
(including humans). Examples: Development of antibiotics,
development of new drugs.

18. In – Vitro Studies.
• Known as "test tube" experiments. These are the studies
performed with microorganisms, cells or biological molecules
outside their normal biological context.
• These are performed in labwares.

19. Models for IDDM. (Type-1)
• Chemically Induced Diabetes.
a)Alloxan
b)Streptozotocin
• Harmones Induced Diabetes.
• Viruses Induced Diabetes.
• Surgical Induced Diabetes.
• Insulin antibodies Induced Diabetes.

20. Models for NIDDM (Type-2)
• Chemically Induced Diabetes.
a) Neonatal STZ Model for NIDDM
• Genetic Models.
a) Zucker diabetic Fatty Rat (ZDF).
b) Wdf/Ta-Fa Rat.
• Transgenic and knockout Animals.

21. Chemically Induced Diabetes.
1. Alloxan Induced Diabetes.
Principle:-
• Alloxan have capacity to produce reversible diabetes.
• It is a toxic cyclic urea which destroys Beta cells of Islets of langerhans
in pancreas.
• This compound causes severe necrosis of pancreatic Beta cells.
• It has been suggested that alloxan-induced the production of H2O2
and some free radicals such as O2 and that produce first damage and
later that death of Beta cells.

23. Procedure:-
• 1. Animals: Rats of Wistar or Sprague - Dawley strain (150-200 g)
• 2. Inducing agent: Alloxan (100-175 mg / kg s.c.)
• 3. Maintain rats at standard environment and laboratory chow.
• 4. All the animals, which are given alloxan, receive glucose and insulin for
one week and food ad libitum.
• 5. Thereafter, a single daily dose of 28 IU insulin is administered S.C.
• 6. The blood glucose level shows triphasic change, first a rise at 2Hr,
followed by hypoglycemic phase at 8Hr and finally an increase at 24Hr
probably due to depletion of B - cells of insulin.

24. Evaluation:
Any suitable method of estimation of :
1. Glucose Level
2. Insulin level
3. Hepatic Glycogen level.
Compare Results of standard with control group animals.

25. Drawbacks:
1. High mortality in rats.
2. Diabetes induced is reversible.
3. Some species like Guinea pigs are resistant to its diabetogenic
action.
Alloxan has been almost completely replaced by
streptozotocin stz because of these drawbacks.

26. Streptozocin Induced Diabetes.
• STZ 12 - deoxy - 2- (3 - methyl - 3 - nitrosourea) 1 - D - glucopyranose)
• It is a broad - spectrum antibiotic, which is produced from
Streptomyces achromogens .
• It is used to induce both type 1 diabetes and type 2 diabetes at dose
of 50mg / kg ip for 3 days and 80-100mg / kg (iv, ip or s.) in neonatal
rats for 10days respectively .
• Mechanism of causing B - cell damage
• a) By process of methylation
• b) Free radical generation and
• c) Nitric oxide production

27. Procedure :
• 1. STZ induces diabetes in almost all species of animals.
• Diabetic dose varies with species and the optimal doses required in
various species are:
a) Rats (50-60mg / kg, ip. Or iv)
b Mice (175-200mg / kg, ip or iv)
c) Dogs (15 mg / kg for 3 days)
2. The blood glucose level shows the same triphasic response as seen
in the alloxan treated animals, with hyperglycemia at 1Hr followed by
hypoglycemia which lasts for 6 Hr, and stable hyperglycemia by 24-48Hr
after STZ administration.

28. Advantages:
• It has completely replaced Alloxan for inducing diabetes because of:
1. Greater selectivity towards B - cells
2. Lower mortality rate
3. Irreversible diabetes induction

29. Harmones Induced Diabetes.
• Animal: Rats, Guinea pigs and Rabbits.
• Inducing hormone: Dexamethasone.
• Eg. NIDDM form of diabetes is induced when dexamethasone, a long
- acting glucocorticoid is administered at a dose of 2-5mg / kg ip.
twice a dayin rats.
• In these models, corticotrophin is used to stimulate the adrenal
cortex that results in hormonal imbalance causing steroidal diabetes.

30. Surgically Induced Diabetes.
• Surgical removal of all part of pancreas total removal of pancreas
results in the insulin dependent type of diabetes experimental
animals are required to maintain insulin therapy.

31. Models for NIDDM (Type-2)
1. Zucker Diabetic Fatty Rat (ZDF)
• Diabetes with hyperglycemia is observed.
• Less obese but more insulin resistance than Zucker Fatty rats.
• Down regulation of B - cell hence impaired insulin synthesis.
• Male and female becomes diabetic at the age of 6-8 weeks and 9-11
weeks respectively.
• Characterized by Hyperglycemia, moderate hyperinsulinimia.

32. Zucker Diabetic Fatty Rats.

33. 2.Wdf/Ta-Fa Rat
• Commonly referred to as Wistar fatty rat.
• They are Genetically obese rats.
• Rats established by transfer of fatty (fa) gene from Zucker fatty rat to
Wister Kyoto rat.
• More glucose intolerance and insulin resistance than Zucker rats.
• Female rats do not show diabetes induced by sucrose rich diet.

34. Wdf/Ta-Fa Rat.

35. In-Vitro Models.
1. Isolated Pancreas of Rat.
2. Isolated Rat Liver.
3. Isolated Hepatocytes.
4. Isolated target tissue.
5. Assay of Amylase Inhibition.
6. Assay of alpha-glucosidase activity.

36. Thank You