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!