36 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
Myocardial contractile function and 6-minute hall walk test.
<p>Tissue-Doppler mitral plane longitudinal maximal velocity (S'max) in <b>A:</b> T2D-HF group and <b>B:</b> T2D-nonHF group during resting state. <b>C:</b> 6-minute hall walk test performed in the T2D-HF group (C). No: normoglycemia; Hy: hyperglycemia. * Difference (hyper- vs normoglycemia): 9%, p = 0.04. †Difference: (hyper- vs normoglycemia): 10%, p<0.001. ††Mean difference 26 meter corresponding to 7%, p = 0.02, paired t-test.</p
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
Echocardiographic and exercise measurements.
<p>Echocardiographic measurements and bicycle exercise test for each study group. Values are mean±SD. Two-way ANOVA with repeated measurements revealed no significant interaction. Underlined values indicate p<0.05.</p>*<p>: p-value <0.001,</p>**<p>: p-value <0.01,</p>†<p>: p-value <0.05 between normoglycemia vs. hyperglycemia (Student-Newman-Keuls post-hoc analysis).</p><p>Nor: Normoglycemia. Hyp: Hyperglycemia. LVEF: left ventricular ejection fraction. S'max: longitudinal mitral plane maximal velocity. Vmax: Global myocardial maximal systolic tissue velocity.</p
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
Glucose levels.
<p>Hourly glucose measurements in both study groups (T2D-HF and T2D-nonHF) during both interventions (hyperglycemia and normoglycemia). Glucose levels differed significant between hyperglycemia and normoglycemia (p<0.001, two-way ANOVA with repeated measurements) in both study groups (T2D-HF: p<0.001, T2D-nonHF: p<0.001). Neither during hyper- (p = 0.28) nor normoglycemia (0.24) did the two study populations differ with respect to glucose levels (bars indicating mean±SEM).</p