PMID- 38525051
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240326
IS  - 1179-1454 (Print)
IS  - 1179-1454 (Electronic)
IS  - 1179-1454 (Linking)
VI  - 16
DP  - 2024
TI  - Dapagliflozin Pretreatment Prevents Cardiac Electrophysiological Changes in a 
      Diet and Streptozotocin Induction of Type 2 Diabetes in Rats: A Potential New 
      First-Line?
PG  - 123-133
LID - 10.2147/JEP.S443169 [doi]
AB  - PURPOSE: Dapagliflozin exerts cardioprotective effects in Type 2 Diabetes 
      Mellitus (T2DM). However, whether these effects prevent electrocardiographic 
      changes associated with T2DM altogether remain unknown. Our aim was to 
      investigate the prophylactic effect of dapagliflozin pretreatment on the rat ECG 
      using a high-fat, high-fructose (HFHf) diet and a low dose streptozotocin (STZ) 
      model of T2DM. METHODS: Twenty-five (25) rats were randomized into five (5) 
      groups: normal control receiving a normal diet while the other groups received an 
      8-week HFHf and 40mg/kg STZ on day 42, and either: saline for the diabetic 
      control (1 mg/kg/d), low dose (1.0 mg/kg/d) and high dose dapagliflozin (1.6 
      mg/kg/d), or metformin (250 mg/kg/d). Oral glucose tolerance (OGT), 
      electrocardiograms (ECGs), paracardial adipose mass, and left ventricular 
      fibrosis were determined. Data were analyzed using GraphPad version 9.0.0.121, 
      with the level of significance at p < 0.05. RESULTS: Compared to the diabetic 
      control group, a high dose of dapagliflozin preserved the OGT (p = 0.0001), 
      QRS-duration (p = 0.0263), QT-interval (p = 0.0399), and QTc intervals (p = 
      0.0463). Furthermore, the high dose dapagliflozin group had the lowest 
      paracardial adipose mass (p = 0.0104) and fibrotic area (p = 0.0001). In 
      contrast, while metformin showed favorable effects on OGT (p = 0.0025), 
      paracardial adiposity (p = 0.0153) and ventricular fibrosis (p = 0.0291), it did 
      not demonstrate significant antiarrhythmic effects. CONCLUSION: Pretreatment with 
      higher doses of Dapagliflozin exhibits prophylactic cardioprotective 
      characteristics against diabetic cardiomyopathy that include antifibrotic and 
      antiarrhythmic qualities. This suggests that higher doses of dapagliflozin could 
      be a more effective initial therapeutic option in T2DM.
CI  - (c) 2024 Juttla et al.
FAU - Juttla, Prabhjot Kaur
AU  - Juttla PK
AUID- ORCID: 0009-0003-7227-7949
AD  - Department of Medical Physiology, University of Nairobi, Nairobi, Kenya.
FAU - Chege, Boniface Mwangi
AU  - Chege BM
AUID- ORCID: 0000-0001-8892-3552
AD  - School of Health Sciences, Dedan Kimathi University of Technology, Nyeri, Kenya.
FAU - Mwangi, Peter Waweru
AU  - Mwangi PW
AD  - Department of Medical Physiology, University of Nairobi, Nairobi, Kenya.
FAU - Bukachi, Frederick
AU  - Bukachi F
AD  - Department of Medical Physiology, University of Nairobi, Nairobi, Kenya.
LA  - eng
PT  - Journal Article
DEP - 20240320
PL  - New Zealand
TA  - J Exp Pharmacol
JT  - Journal of experimental pharmacology
JID - 101530345
PMC - PMC10961018
OTO - NOTNLM
OT  - animal model
OT  - diabetic cardiomyopathy
OT  - electrocardiogram
OT  - prophylaxis
OT  - sodium glucose co-transporter inhibitors
COIS- The authors report no conflicts of interest in this work.
EDAT- 2024/03/25 06:43
MHDA- 2024/03/25 06:44
PMCR- 2024/03/20
CRDT- 2024/03/25 04:35
PHST- 2023/10/15 00:00 [received]
PHST- 2024/02/22 00:00 [accepted]
PHST- 2024/03/25 06:44 [medline]
PHST- 2024/03/25 06:43 [pubmed]
PHST- 2024/03/25 04:35 [entrez]
PHST- 2024/03/20 00:00 [pmc-release]
AID - 443169 [pii]
AID - 10.2147/JEP.S443169 [doi]
PST - epublish
SO  - J Exp Pharmacol. 2024 Mar 20;16:123-133. doi: 10.2147/JEP.S443169. eCollection 
      2024.