PMID- 27530514
OWN - NLM
STAT- MEDLINE
DCOM- 20170217
LR  - 20181202
IS  - 1879-0631 (Electronic)
IS  - 0024-3205 (Linking)
VI  - 162
DP  - 2016 Oct 1
TI  - Cardioprotective role of peroxisome proliferator-activated receptor-gamma agonist, 
      rosiglitazone in a unique murine model of diabetic cardiopathy.
PG  - 1-13
LID - S0024-3205(16)30475-1 [pii]
LID - 10.1016/j.lfs.2016.08.013 [doi]
AB  - AIMS: Rosiglitazone (RSZ), a PPARgamma agonist was potent efficacious insulin 
      sensitizing blockbuster drug for treatment of Type 2 diabetes mellitus (T2DM) but 
      the benefit of PPARgamma activation in congestive heart failure (CHF) was 
      controversial. The present work was planned to study the role of RSZ in diabetic 
      cardiopathy. MAIN METHODS: Zucker fa/fa rats, the genetic model of T2DM were 
      subjected to constriction of suprarenal abdominal aorta so that they represent a 
      combined model of diabetes and cardiopathy. The development cardiopathy was 
      assessed biochemically (plasma BNP and aldosterone levels), using 
      echocardiography and expression angiotensin II receptor type 1a gene in heart and 
      Endothelin-1 gene in aorta. Rats were treated with RSZ and in combination with 
      amiloride for four weeks and were assessed to evaluate the effect of RSZ or 
      amiloride or its combination on antidiabetic activity, adverse or toxic effects 
      and congestive heart failure status. KEY FINDINGS: RSZ shows its anti-diabetic 
      effect from 0.3mg/kg dose onwards and at 3mg/kg dose levels it caused beneficial 
      effects (reduction of blood pressure) on cardiovascular system and at highest 
      (30mg/kg) dose it starts showing adverse effects like body weight gain, edema, 
      left ventricular hypertrophy. However, when highest dose of RSZ animals were 
      treated with amiloride (ENaC inhibitor) at 2mg/kg the reversal of the adverse 
      effects was evident, indicating the combination of RSZ and amiloride is 
      beneficial in diabetic cardiopathy model. SIGNIFICANCE: RSZ and amiloride 
      combination appeared promising treatment in diabetic patients with cardiopathy 
      without any side effect.
CI  - Copyright (c) 2016 Elsevier Inc. All rights reserved.
FAU - Giri, Suresh R
AU  - Giri SR
AD  - Department of Pharmacology & Toxicology, Zydus Research Centre, Cadila Healthcare 
      Limited, Sarkhej-Bavla N.H. No. 8A, Moraiya, Ahmedabad 382 213, Gujarat, India; 
      Department of Pharmacology & Toxicology, Bombay Veterinary College, Parel, Mumbai 
      400012, India. Electronic address: drsureshgiri76@gmail.com.
FAU - Bhoi, Bibhuti
AU  - Bhoi B
AD  - Department of Pharmacology & Toxicology, Zydus Research Centre, Cadila Healthcare 
      Limited, Sarkhej-Bavla N.H. No. 8A, Moraiya, Ahmedabad 382 213, Gujarat, India.
FAU - Jain, Mukul R
AU  - Jain MR
AD  - Department of Pharmacology & Toxicology, Zydus Research Centre, Cadila Healthcare 
      Limited, Sarkhej-Bavla N.H. No. 8A, Moraiya, Ahmedabad 382 213, Gujarat, India.
FAU - Gatne, Madhumanjiri M
AU  - Gatne MM
AD  - Department of Pharmacology & Toxicology, Bombay Veterinary College, Parel, Mumbai 
      400012, India.
LA  - eng
PT  - Journal Article
DEP - 20160813
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (PPAR gamma)
RN  - 0 (Thiazolidinediones)
RN  - 05V02F2KDG (Rosiglitazone)
SB  - IM
MH  - Animals
MH  - Aorta/metabolism
MH  - Diabetes Complications
MH  - *Disease Models, Animal
MH  - Gene Expression
MH  - Heart Failure/*drug therapy/etiology
MH  - Hypoglycemic Agents/*therapeutic use
MH  - Kidney/metabolism
MH  - Mice
MH  - Myocardium/metabolism
MH  - PPAR gamma/*agonists
MH  - Rats
MH  - Rats, Zucker
MH  - Rosiglitazone
MH  - Thiazolidinediones/*therapeutic use
OTO - NOTNLM
OT  - Amiloride
OT  - Diabetic cardiopathy
OT  - PPAR gamma agonist
OT  - Rosiglitazone
OT  - Type 2 diabetes mellitus
EDAT- 2016/08/18 06:00
MHDA- 2017/02/18 06:00
CRDT- 2016/08/18 06:00
PHST- 2016/04/07 00:00 [received]
PHST- 2016/08/09 00:00 [revised]
PHST- 2016/08/12 00:00 [accepted]
PHST- 2016/08/18 06:00 [entrez]
PHST- 2016/08/18 06:00 [pubmed]
PHST- 2017/02/18 06:00 [medline]
AID - S0024-3205(16)30475-1 [pii]
AID - 10.1016/j.lfs.2016.08.013 [doi]
PST - ppublish
SO  - Life Sci. 2016 Oct 1;162:1-13. doi: 10.1016/j.lfs.2016.08.013. Epub 2016 Aug 13.