PMID- 25595459
OWN - NLM
STAT- MEDLINE
DCOM- 20151130
LR  - 20191210
IS  - 1873-4596 (Electronic)
IS  - 0891-5849 (Linking)
VI  - 81
DP  - 2015 Apr
TI  - Association of low GLP-1 with oxidative stress is related to cardiac disease and 
      outcome in patients with type 2 diabetes mellitus: a pilot study.
PG  - 1-12
LID - S0891-5849(15)00009-X [pii]
LID - 10.1016/j.freeradbiomed.2015.01.002 [doi]
AB  - Oxidative stress (OS) contributes to cardiovascular damage in type 2 diabetes 
      mellitus (T2DM). The peptide glucagon-like peptide-1 (GLP-1) inhibits OS and 
      exerts cardiovascular protective actions. Our aim was to investigate whether 
      cardiac remodeling (CR) and cardiovascular events (CVE) are associated with 
      circulating GLP-1 and biomarkers of OS in T2DM patients. We also studied GLP-1 
      antioxidant effects in a model of cardiomyocyte lipotoxicity. We examined 72 T2DM 
      patients with no coronary or valve heart disease and 14 nondiabetic subjects. A 
      median of 6 years follow-up information was obtained in 60 patients. Circulating 
      GLP-1, dipeptidyl peptidase-4 activity, and biomarkers of OS were quantified. In 
      T2DM patients, circulating GLP-1 decreased and OS biomarkers increased, compared 
      with nondiabetics. Plasma GLP-1 was inversely correlated with serum 
      3-nitrotyrosine in T2DM patients. Patients showing high circulating 
      3-nitrotyrosine and low GLP-1 levels exhibited CR and higher risk for CVE, 
      compared to the remaining patients. In palmitate-stimulated HL-1 cardiomyocytes, 
      GLP-1 reduced cytosolic and mitochondrial oxidative stress, increased 
      mitochondrial ATP synthase expression, partially restored mitochondrial membrane 
      permeability and cytochrome c oxidase activity, blunted leakage of creatine to 
      the extracellular medium, and inhibited oxidative damage in total and 
      mitochondrial DNA. These results suggest that T2DM patients with reduced 
      circulating GLP-1 and exacerbated OS may exhibit CR and be at higher risk for 
      CVE. In addition, GLP-1 exerts antioxidant effects in HL-1 palmitate-overloaded 
      cardiomyocytes. It is proposed that therapies aimed to increase GLP-1 may 
      counteract OS, protect from CR, and prevent CVE in patients with T2DM.
CI  - Copyright (c) 2015 Elsevier Inc. All rights reserved.
FAU - Ravassa, Susana
AU  - Ravassa S
AD  - Program of Cardiovascular Diseases, Centre for Applied Medical Research, 
      University of Navarra, Pamplona, Spain. Electronic address: sravassa@unav.es.
FAU - Beaumont, Javier
AU  - Beaumont J
AD  - Program of Cardiovascular Diseases, Centre for Applied Medical Research, 
      University of Navarra, Pamplona, Spain.
FAU - Huerta, Ana
AU  - Huerta A
AD  - Department of Internal Medicine, University of Navarra Clinic, University of 
      Navarra, Pamplona, Spain.
FAU - Barba, Joaquin
AU  - Barba J
AD  - Department of Cardiology and Cardiac Surgery, University of Navarra Clinic, 
      University of Navarra. Pamplona, Spain.
FAU - Coma-Canella, Isabel
AU  - Coma-Canella I
AD  - Department of Cardiology and Cardiac Surgery, University of Navarra Clinic, 
      University of Navarra. Pamplona, Spain.
FAU - Gonzalez, Arantxa
AU  - Gonzalez A
AD  - Program of Cardiovascular Diseases, Centre for Applied Medical Research, 
      University of Navarra, Pamplona, Spain.
FAU - Lopez, Begona
AU  - Lopez B
AD  - Program of Cardiovascular Diseases, Centre for Applied Medical Research, 
      University of Navarra, Pamplona, Spain.
FAU - Diez, Javier
AU  - Diez J
AD  - Program of Cardiovascular Diseases, Centre for Applied Medical Research, 
      University of Navarra, Pamplona, Spain; Department of Cardiology and Cardiac 
      Surgery, University of Navarra Clinic, University of Navarra. Pamplona, Spain.
LA  - eng
PT  - Clinical Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150113
PL  - United States
TA  - Free Radic Biol Med
JT  - Free radical biology & medicine
JID - 8709159
RN  - 0 (Antioxidants)
RN  - 2V16EO95H1 (Palmitic Acid)
RN  - 3604-79-3 (3-nitrotyrosine)
RN  - 42HK56048U (Tyrosine)
RN  - 88847-89-6 (8-Hydroxy-2'-Deoxyguanosine)
RN  - 89750-14-1 (Glucagon-Like Peptide 1)
RN  - EC 3.4.14.5 (DPP4 protein, human)
RN  - EC 3.4.14.5 (Dipeptidyl Peptidase 4)
RN  - G9481N71RO (Deoxyguanosine)
SB  - IM
MH  - 8-Hydroxy-2'-Deoxyguanosine
MH  - Aged
MH  - Animals
MH  - Antioxidants/*metabolism/pharmacology
MH  - Atrial Remodeling
MH  - Cardiomegaly/*blood/etiology/physiopathology
MH  - Cardiovascular System/metabolism/physiopathology
MH  - Case-Control Studies
MH  - Cell Line
MH  - Deoxyguanosine/analogs & derivatives/blood
MH  - Diabetes Mellitus, Type 2/*blood/complications/physiopathology
MH  - Dipeptidyl Peptidase 4/blood
MH  - Female
MH  - Glucagon-Like Peptide 1/*blood/pharmacology
MH  - Humans
MH  - Male
MH  - Mice
MH  - Middle Aged
MH  - Mitochondria/drug effects/metabolism
MH  - Myocytes, Cardiac/drug effects/*metabolism/pathology
MH  - Oxidative Stress
MH  - Palmitic Acid/antagonists & inhibitors/pharmacology
MH  - Pilot Projects
MH  - Retrospective Studies
MH  - Tyrosine/analogs & derivatives/blood
MH  - Ventricular Remodeling
OTO - NOTNLM
OT  - Cardiac remodeling
OT  - Cardiovascular events
OT  - GLP-1
OT  - Oxidative stress
OT  - Type 2 diabetes mellitus
EDAT- 2015/01/18 06:00
MHDA- 2015/12/15 06:00
CRDT- 2015/01/18 06:00
PHST- 2014/09/08 00:00 [received]
PHST- 2014/12/23 00:00 [revised]
PHST- 2015/01/04 00:00 [accepted]
PHST- 2015/01/18 06:00 [entrez]
PHST- 2015/01/18 06:00 [pubmed]
PHST- 2015/12/15 06:00 [medline]
AID - S0891-5849(15)00009-X [pii]
AID - 10.1016/j.freeradbiomed.2015.01.002 [doi]
PST - ppublish
SO  - Free Radic Biol Med. 2015 Apr;81:1-12. doi: 10.1016/j.freeradbiomed.2015.01.002. 
      Epub 2015 Jan 13.