1. FIRST AUTHOR: DOINA GHERESCU OTHER AUTHORS: ADRIANA VÂNTU PAUL-CIPRIAN FIC Ă MARCEL PERIAN R Ă ZVAN CONSTANTIN ERBAN Coordinators: Prof. Dr. Dan Dobreanu Ass. Prof. Dr. Alina Scridon

2. Background Diabetes mellitus (DM) = a complex chronic metabolic disease characterized by: hyperglycemia - carbohydrate impaired - lipid metabolism - protein Our study!

3. Background Experimental models ─ essential for clarifying the pathogenesis and progression of the disease. therapeutic strategies

4. Objective Long-term follow-up on Wistar rats with Streptozotocin induced type 1 Diabetes mellitus Success and mortality rates Reinjection – is it efficient?

5. Materials and Methods 31 6-week-old Wistar rats Control n=14 Diabetes mellitus n=17 Initial bodyweight: 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 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

6. Materials and Methods For 28 weeks weeklyBodyweightFood intake Water intake 11 and 38 weeks Systolic BP Heart Rate

7. Materials and Methods Noninvasive photopletismography method using a pneumatic tail cuff

8. Results Succes rates of Streptozotocin administration Overall success: 88.23%

9. Results Mortality rates Control => 0 deaths Diabetes mellitus => 4 deaths out of 17 rats (23.5 %) 2 STZ- reinjected (unsuccessfull) 2 DM-related

10. Results Long-term evolution of bodyweight Spearman r = 0.71, p< 0.001 Spearman r = 0.30, p< 0.001 365.46 ± 10.03g 511.43 ± 13.54g

11. Results Long-term evolution of food intake 44.64 ± 2.31 g/24h 25.86 ± 0.88 g/24h p<0.001

12. Results Long-term evolution of water intake 78.57 ± 2.43 ml/24h 210.71 ± 13.55 ml/24h p<0.001

13. Results Systolic blood pressure

14. Results Heart rate p<0.001

15. Results 1 STZ vs 2 STZ

16. 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

17. 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

18. 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

19. Thank you very much for your attention!