Type 2 diabetes mellitus worsens neurological injury following cardiac arrest: an animal experimental study

Abstract Background Cardiac arrest carries a poor prognosis. The typical cardiac arrest patient is comorbid, and studies have shown that diabetes mellitus is an independent risk factor for increased mortality after cardiac arrest. Despite this, animal studies lack to investigate cardiac arrest in the setting of diabetes mellitus. We hypothesize that type 2 diabetes mellitus in a rat model of cardiac arrest is associated with increased organ dysfunction when compared with non-diabetic rats. Methods Zucker diabetic fatty (ZDF) rats (n = 13), non-diabetic Zucker lean control (ZLC) rats (n = 15), and non-diabetic Sprague Dawley (SprD) rats (n = 8), underwent asphyxia-induced cardiac arrest. Animals were resuscitated and monitored for 180 min after return of spontaneous circulation (ROSC). Blood levels of neuron-specific enolase were measured to assess neurological injury. Cardiac function was evaluated by echocardiography. Results No differences in cardiac output or neuron-specific enolase existed between the groups at baseline. Median levels of neuron-specific enolase 180 min after ROSC was 10.8 μg/L (Q25;Q75—7.6;11.3) in the ZDF group, which was significantly higher compared to the ZLC group at 2.0 μg/L (Q25;Q75—1.7;2.3, p < 0.05) and the SprD group at 2.8 μg/L (Q25;Q75—2.3;3.4, p < 0.05). At 180 min after ROSC, cardiac output was 129 mL/min/kg (SD 45) in the ZDF group, which was not different from 106 mL/min/kg (SD 31) in the ZLC group or 123 mL/min/kg (SD 26, p = 0.72) in the SprD group. Conclusions In a cardiac arrest model, neuronal injury is increased in type 2 diabetes mellitus animals compared with non-diabetic controls. Although this study lacks to uncover the specific mechanisms causing increased neuronal injury, the establishment of a cardiac arrest model of type 2 diabetes mellitus lays the important foundation for further experimental investigations within this field

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