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FIRST AUTHOR: DOINA GHERESCU OTHER AUTHORS: ADRIANA VÂNTU PAUL-CIPRIAN FIC Ă MARCEL PERIAN R Ă...
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Transcript of FIRST AUTHOR: DOINA GHERESCU OTHER AUTHORS: ADRIANA VÂNTU PAUL-CIPRIAN FIC Ă MARCEL PERIAN R Ă...
Long-term follow-up of type 1 diabetic Wistar rats
FIRST AUTHOR: DOINA GHERȚESCU
OTHER AUTHORS: ADRIANA VÂNTU
PAUL-CIPRIAN FIȘCĂ
MARCEL PERIAN
RĂZVAN CONSTANTIN ȘERBAN
Coordinators: Prof. Dr. Dan Dobreanu Ass. Prof. Dr. Alina Scridon
Background
Diabetes mellitus (DM) = a complex chronic metabolic disease characterized by:
hyperglycemia
- carbohydrate
impaired - lipid metabolism
- protein
Our study!
Background
Experimental models ─ essential for clarifying the pathogenesis and progression of the disease.
therapeutic strategies
Objective
Long-term follow-up on Wistar rats with Streptozotocin induced type 1 Diabetes mellitus
Success and mortality rates
Reinjection – is it efficient?
Materials and Methods
31 6-week-old Wistar rats
Controln=14
Diabetes mellitus
n=17
Initial bodyweig
ht:177.88 ±
4.01 g 11 weeks – Streptozotocin injection (i.p. 60 mg/kg of bw)
12 weeks – if plasma glucose ≥ 250 mg/dl => Diabetics
< 250 mg/dl => Reinjection
o Streptozotocin (STZ) = a cytotoxic glucose analogue that
preferentially accumulates in pancreatic β-cells.
o The most widely used diabetogenic chemical in DM
research
Materials and Methods
For 28 weeks
weekly
Bodyweight
Food intake
Water intake
11 and 38 weeks
SystolicBP
HeartRate
Materials and MethodsNoninvasive photopletismography method using a pneumatic tail cuff
ResultsSucces rates of Streptozotocin administration
58.82%29.41%
11.77%
Succes Rates
1 injection 2 injections Failure
Overall success: 88.23%
ResultsMortality rates
Control => 0 deathsDiabetes mellitus => 4 deaths out of 17 rats (23.5 %)
2 STZ-reinjected
(unsuccessfull)
2 DM-related
ResultsLong-term evolution of bodyweight
5 10 15 20 25 30 35 40100
200
300
400
500
600
Bodyweight
Control DM
Age (weeks)
Bodyw
eig
ht
(g)
Spearman r = 0.71, p< 0.001
Spearman r = 0.30, p< 0.001365.46 ± 10.03g
511.43 ± 13.54g
ResultsLong-term evolution of food intake
6 11 16 21 26 31 36 410
10
20
30
40
50
60 Food intakeControl DM
Age (weeks)
Fo
od
in
take
(g
/24
h)
44.64 ± 2.31 g/24h
25.86 ± 0.88 g/24h
p<0.001
ResultsLong-term evolution of water intake
6 11 16 21 26 31 36 410
50
100
150
200
250Water intake
Control DM
Age (weeks)
Wate
r in
take (
ml/24 h
)
78.57 ± 2.43 ml/24h
210.71 ± 13.55 ml/24h
p<0.001
ResultsSystolic blood pressure
11 weeks 38 weeks0
40
80
120
160
126.07141.71
127.41 134.50
Systolic Blood Pressure
Age
Sys
tolic
Blo
od P
ress
ure
(m
mH
g)
p<0.01
ResultsHeart rate
11 weeks 38 weeks0
100
200
300
400
319.21388.57
311.53 293.10
Heart Rate
Age
Heart
Rate
(bpm
)
p<0.001
p<0.001
Results1 STZ vs 2 STZ
0
100
200
300
400
500
600
377.63
47.25
215.63
137.2
286.43
521.63
346
39.2
190
130.2
279.4
489.21 STZ vs 2 STZ
Diabetes mellitus (1 STZ) Diabetes mellitus (2 STZ)
Discussion
High success Low mortality
rates
Diabetic rats - a modest gain in bodyweight + significantly increased food and water consumption
STZ-induced DM model in Wistar rats mimics the clinical signs of human patients with type
1 DM
Discussion
The different response in SBP and HR - impaired autonomic balance with vagal hyperactivity
STZ reinjection - safe and efficient => a fact of great procedural importance in long-term studies
Conclussion
One of the most detailed, long-term follow-ups of the most widely used experimental model of type 1 DM
▪The first one to demonstrate that STZ can be safely reinjected, without any changes in rats’ outcomes
▪The STZ-diabetic rat – useful experimental model that reliably replicates many of the major clinical signs of type 1 human DM
Thank you very much for your attention!