24 research outputs found
Proteomics of the Rat Myocardium during Development of Type 2 Diabetes Mellitus Reveals Progressive Alterations in Major Metabolic Pathways
Congestive heart failure and poor
clinical outcome after myocardial
infarction are known complications in patients with type-2 diabetes
mellitus (T2DM). Protein alterations may be involved in the mechanisms
underlying these disarrays in the diabetic heart. Here we map proteins
involved in intracellular metabolic pathways in the Zucker diabetic
fatty rat heart as T2DM develops using MS based proteomics. The prediabetic
state only induced minor pathway changes, whereas onset and late T2DM
caused pronounced perturbations. Two actin-associated proteins, ARPC2
and TPM3, were up-regulated at the prediabetic state indicating increased
actin dynamics. All differentially regulated proteins involved in
fatty acid metabolism, both peroxisomal and mitochondrial, were up-regulated
at late T2DM, whereas enzymes of branched chain amino acid degradation
were all down-regulated. At both onset and late T2DM, two members
of the serine protease inhibitor superfamily, SERPINA3K and SERPINA3L,
were down-regulated. Furthermore, we found alterations in proteins
involved in clearance of advanced glycation end-products and lipotoxicity,
DCXR and CBR1, at both onset and late T2DM. These proteins deserve
elucidation with regard to their role in T2DM pathogenesis and their
respective role in the deterioration of the diabetic heart. Data are
available via ProteomeXchange with identifiers PXD009538, PXD009554,
and PXD009555
Proteomics of the Rat Myocardium during Development of Type 2 Diabetes Mellitus Reveals Progressive Alterations in Major Metabolic Pathways
Congestive heart failure and poor
clinical outcome after myocardial
infarction are known complications in patients with type-2 diabetes
mellitus (T2DM). Protein alterations may be involved in the mechanisms
underlying these disarrays in the diabetic heart. Here we map proteins
involved in intracellular metabolic pathways in the Zucker diabetic
fatty rat heart as T2DM develops using MS based proteomics. The prediabetic
state only induced minor pathway changes, whereas onset and late T2DM
caused pronounced perturbations. Two actin-associated proteins, ARPC2
and TPM3, were up-regulated at the prediabetic state indicating increased
actin dynamics. All differentially regulated proteins involved in
fatty acid metabolism, both peroxisomal and mitochondrial, were up-regulated
at late T2DM, whereas enzymes of branched chain amino acid degradation
were all down-regulated. At both onset and late T2DM, two members
of the serine protease inhibitor superfamily, SERPINA3K and SERPINA3L,
were down-regulated. Furthermore, we found alterations in proteins
involved in clearance of advanced glycation end-products and lipotoxicity,
DCXR and CBR1, at both onset and late T2DM. These proteins deserve
elucidation with regard to their role in T2DM pathogenesis and their
respective role in the deterioration of the diabetic heart. Data are
available via ProteomeXchange with identifiers PXD009538, PXD009554,
and PXD009555
Proteomics of the Rat Myocardium during Development of Type 2 Diabetes Mellitus Reveals Progressive Alterations in Major Metabolic Pathways
Congestive heart failure and poor
clinical outcome after myocardial
infarction are known complications in patients with type-2 diabetes
mellitus (T2DM). Protein alterations may be involved in the mechanisms
underlying these disarrays in the diabetic heart. Here we map proteins
involved in intracellular metabolic pathways in the Zucker diabetic
fatty rat heart as T2DM develops using MS based proteomics. The prediabetic
state only induced minor pathway changes, whereas onset and late T2DM
caused pronounced perturbations. Two actin-associated proteins, ARPC2
and TPM3, were up-regulated at the prediabetic state indicating increased
actin dynamics. All differentially regulated proteins involved in
fatty acid metabolism, both peroxisomal and mitochondrial, were up-regulated
at late T2DM, whereas enzymes of branched chain amino acid degradation
were all down-regulated. At both onset and late T2DM, two members
of the serine protease inhibitor superfamily, SERPINA3K and SERPINA3L,
were down-regulated. Furthermore, we found alterations in proteins
involved in clearance of advanced glycation end-products and lipotoxicity,
DCXR and CBR1, at both onset and late T2DM. These proteins deserve
elucidation with regard to their role in T2DM pathogenesis and their
respective role in the deterioration of the diabetic heart. Data are
available via ProteomeXchange with identifiers PXD009538, PXD009554,
and PXD009555
Proteomics of the Rat Myocardium during Development of Type 2 Diabetes Mellitus Reveals Progressive Alterations in Major Metabolic Pathways
Congestive heart failure and poor
clinical outcome after myocardial
infarction are known complications in patients with type-2 diabetes
mellitus (T2DM). Protein alterations may be involved in the mechanisms
underlying these disarrays in the diabetic heart. Here we map proteins
involved in intracellular metabolic pathways in the Zucker diabetic
fatty rat heart as T2DM develops using MS based proteomics. The prediabetic
state only induced minor pathway changes, whereas onset and late T2DM
caused pronounced perturbations. Two actin-associated proteins, ARPC2
and TPM3, were up-regulated at the prediabetic state indicating increased
actin dynamics. All differentially regulated proteins involved in
fatty acid metabolism, both peroxisomal and mitochondrial, were up-regulated
at late T2DM, whereas enzymes of branched chain amino acid degradation
were all down-regulated. At both onset and late T2DM, two members
of the serine protease inhibitor superfamily, SERPINA3K and SERPINA3L,
were down-regulated. Furthermore, we found alterations in proteins
involved in clearance of advanced glycation end-products and lipotoxicity,
DCXR and CBR1, at both onset and late T2DM. These proteins deserve
elucidation with regard to their role in T2DM pathogenesis and their
respective role in the deterioration of the diabetic heart. Data are
available via ProteomeXchange with identifiers PXD009538, PXD009554,
and PXD009555
Proteomics of the Rat Myocardium during Development of Type 2 Diabetes Mellitus Reveals Progressive Alterations in Major Metabolic Pathways
Congestive heart failure and poor
clinical outcome after myocardial
infarction are known complications in patients with type-2 diabetes
mellitus (T2DM). Protein alterations may be involved in the mechanisms
underlying these disarrays in the diabetic heart. Here we map proteins
involved in intracellular metabolic pathways in the Zucker diabetic
fatty rat heart as T2DM develops using MS based proteomics. The prediabetic
state only induced minor pathway changes, whereas onset and late T2DM
caused pronounced perturbations. Two actin-associated proteins, ARPC2
and TPM3, were up-regulated at the prediabetic state indicating increased
actin dynamics. All differentially regulated proteins involved in
fatty acid metabolism, both peroxisomal and mitochondrial, were up-regulated
at late T2DM, whereas enzymes of branched chain amino acid degradation
were all down-regulated. At both onset and late T2DM, two members
of the serine protease inhibitor superfamily, SERPINA3K and SERPINA3L,
were down-regulated. Furthermore, we found alterations in proteins
involved in clearance of advanced glycation end-products and lipotoxicity,
DCXR and CBR1, at both onset and late T2DM. These proteins deserve
elucidation with regard to their role in T2DM pathogenesis and their
respective role in the deterioration of the diabetic heart. Data are
available via ProteomeXchange with identifiers PXD009538, PXD009554,
and PXD009555
Proteomics of the Rat Myocardium during Development of Type 2 Diabetes Mellitus Reveals Progressive Alterations in Major Metabolic Pathways
Congestive heart failure and poor
clinical outcome after myocardial
infarction are known complications in patients with type-2 diabetes
mellitus (T2DM). Protein alterations may be involved in the mechanisms
underlying these disarrays in the diabetic heart. Here we map proteins
involved in intracellular metabolic pathways in the Zucker diabetic
fatty rat heart as T2DM develops using MS based proteomics. The prediabetic
state only induced minor pathway changes, whereas onset and late T2DM
caused pronounced perturbations. Two actin-associated proteins, ARPC2
and TPM3, were up-regulated at the prediabetic state indicating increased
actin dynamics. All differentially regulated proteins involved in
fatty acid metabolism, both peroxisomal and mitochondrial, were up-regulated
at late T2DM, whereas enzymes of branched chain amino acid degradation
were all down-regulated. At both onset and late T2DM, two members
of the serine protease inhibitor superfamily, SERPINA3K and SERPINA3L,
were down-regulated. Furthermore, we found alterations in proteins
involved in clearance of advanced glycation end-products and lipotoxicity,
DCXR and CBR1, at both onset and late T2DM. These proteins deserve
elucidation with regard to their role in T2DM pathogenesis and their
respective role in the deterioration of the diabetic heart. Data are
available via ProteomeXchange with identifiers PXD009538, PXD009554,
and PXD009555
Proteomics of the Rat Myocardium during Development of Type 2 Diabetes Mellitus Reveals Progressive Alterations in Major Metabolic Pathways
Congestive heart failure and poor
clinical outcome after myocardial
infarction are known complications in patients with type-2 diabetes
mellitus (T2DM). Protein alterations may be involved in the mechanisms
underlying these disarrays in the diabetic heart. Here we map proteins
involved in intracellular metabolic pathways in the Zucker diabetic
fatty rat heart as T2DM develops using MS based proteomics. The prediabetic
state only induced minor pathway changes, whereas onset and late T2DM
caused pronounced perturbations. Two actin-associated proteins, ARPC2
and TPM3, were up-regulated at the prediabetic state indicating increased
actin dynamics. All differentially regulated proteins involved in
fatty acid metabolism, both peroxisomal and mitochondrial, were up-regulated
at late T2DM, whereas enzymes of branched chain amino acid degradation
were all down-regulated. At both onset and late T2DM, two members
of the serine protease inhibitor superfamily, SERPINA3K and SERPINA3L,
were down-regulated. Furthermore, we found alterations in proteins
involved in clearance of advanced glycation end-products and lipotoxicity,
DCXR and CBR1, at both onset and late T2DM. These proteins deserve
elucidation with regard to their role in T2DM pathogenesis and their
respective role in the deterioration of the diabetic heart. Data are
available via ProteomeXchange with identifiers PXD009538, PXD009554,
and PXD009555
Infarct size and correlation with blood glucose.
<p><b>A.</b> Infarct size/area-at-risk ratio (IS/AAR). Black bars: Control, White bars: ZDF. <b>B.</b> Correlations between preoperative fasting blood glucose and IS/AAR at prediabetes, onset and late type 2 diabetes mellitus. Mean ± SEM. Circles: ZDF 6 weeks, Squares: ZDF 12 weeks, Triangles: ZDF 24 weeks.</p
Study design and experimental protocol.
<p>Overview of groups, number of animals (<b>N</b>) and experimental protocols. <b>KH-buffer:</b> Krebs-Henseleit buffer.</p
Hemodynamic parameters at baseline and during reperfusion.
<p>Hemodynamic performance during stabilization and reperfusion. Mean±SEM. Closed symbols: Control, Open symbols: ZDF. * p<0.05, † p<0.01, ‡ p<0.001. <b>LVDevP</b>: Left ventricular developed pressure. <b>HR</b>: Heart rate. <b>RPP</b>: rate-pressure-product. <b>RPPrec</b>: % recovery from baseline rate-pressure-product. <b>CF<sub>corr</sub></b>: Coronary flow corrected for heart weight.</p