This document provides information on preclinical screening methods for antidiabetic drugs. It discusses different types of diabetes and methods used to induce diabetes for screening in animal models. The key methods mentioned include chemically-induced diabetes using alloxan and streptozocin in rats, hormone-induced diabetes using dexamethasone in rats, and genetically diabetic mouse and rat models like NOD mice and BB rats. The document also outlines some in vivo and in vitro screening assays used to evaluate potential antidiabetic drug candidates.

1. M pharmacy 1st sem.
Session :- 2020-2021
TOPIC :- Preclinical screening of antidiabetic drugs
Subject code :- MPL 102T
Subject name :- Pharmacological and Toxicological
Screening Methods-1
Submitted By :-
Sachin Gulia
(9003)
Submitted To :-
Abhilasha ma’am
MAHARSHI DYANAND UNIVERSITY

2.  DM is a group of metabolic diseases in which
there are high blood sugar levels over a
prolonged period.
 Diabetes is due to either the pancreas not
producing enough insulin or the cells of the
body not responding properly to the insulin
produced.
 There are mainly two types of DM
a) Type 1 DM
b) Type 2 DM

3.  Insulin dependent diabetes mellitus (IDDM)
 When more than 90% of beta cells of
pancreas are destroyed by an autoimmune
process.
 Result from the pancreas’s failure to produce
enough insulin.
 The cause is unknown

4.  Non Insulin dependent diabetes mellitus
(NIDDM)
 Adult onset diabetes
 Insulin resistance , a condition in which cells
fail to respond to insulin properly
 The primary cause is excessive body weight
and not enough exercise
 It is the commonest form of diabetes.

5. Invivo methods
1. Chemical induced diabetes.
a) Alloxan induced diabetes.
b) Streptozotocin induced diabetes.
c) Monosodium glutamate induced diabetes.
2. Hormone induced DM
a) Growth hormone induced diabetes
b) Corticosteroid induced diabetes
3. Genetically diabetic animals

6. 4. Diabetes induced by viral agents
a) D- variant encephalomyocarditis (EMC-D)
b) Coxsackie viruses
5. Pancreatectomy in dogs
6. Insuline antibodies-induced diabetes
7. Other diabetogenic compounds

7. 1. Isolated pancreas of rat .
2. Isolated rat liver .
3. Isolated target tissue : muscle cell lines .
4. Isolated hepatocytes .
5. Assay for insulin or insulin like substance on
adipocytes .
6. Assay of glucose transport in adipocytes .
7. Assay of amylase inhibition .
8. Assay for lipid synthesis .
9. Glucose uptake by the isolated diaphragm .
from mice and rats .

8. • Male albino rate weighing 150-220g.
• Injected with 120mg/kg alloxan monohydrate
intra-peritoneally (IP) dissolved in 0.9% w/v
cold normal saline to overnight-fasted rats
(12h).
• The rats were afterward kept for the next
24h on 10% glucose solution bottles, in their
cages, to prevent hypoglycemia.

9.  Streptozotocin induced type 2 diabetes.
 IV injection of 60mg/kg dose of
Streptozotocin in adult wistar rats, makes
pancreas swell and induces experimental
diabetes mellitus in the 2-4 days.
 Wistar rats were fed with a high-fat diet for
8 weeks followed by a one-time injection of
25 or 35 mg/kg . Then the diabetic rate were
fed with regular diet/high-fat diet for 4
weeks. Changes in biochemical parameters
were monitored during the 4 weeks.

10.  The rats weighing 150-200gm are selected
and dexamethasone 2-5mg/kg is given IP.
 Repeated injection of same dose level is
carried out for a period of 20-30 days
resulting in diabetes.
 The sample to be screened is administered
through a suitable route, blood glucose is
measured.

11. 1. The non obese diabetic (NOD) mouse
 They are inbred strain of albino mice .
 Develop diabetes abruptly at the 100-200
days of age.
2. The bio breeding(BB) rat
 Onset of clinical diabetes is sudden and
occur at about 60-120 days of age.

12.  Infecting and destroying B-cell in pancreas.
 Viruses producing systemic effects, not
directly affecting B-cell .
 Virus inducing diabetes include :-
a) RNA picornoviruses
b) Coxsackie-B4
c) Mengo-2T

13. THANK YOU