Differential effects of insulin deprivation and systemic insulin treatment on plasma protein synthesis in type 1 diabetic people

Jaleel, Abdul; Klaus, Katherine A.; Morse, Dawn M.; Karakelides, Helen; Ward, L. Emmerson; Irving, Brian A.; Nair, K. Sreekumaran

doi:10.1152/ajpendo.00351.2009

Cited by 20 publications

(21 citation statements)

References 34 publications

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“…Reduction of systemic insulin levels in type 1 diabetic patients is also associated with alterations in plasma protein synthesis (8). Although it had been proposed that such mechanisms were consistent across insulin-sensitive tissues and characteristic of diabetes, studies of brain and kidney have demonstrated otherwise.…”

Section: Introductionmentioning

confidence: 99%

mTORC1-Independent Reduction of Retinal Protein Synthesis in Type 1 Diabetes

et al. 2014

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Poorly controlled diabetes has long been known as a catabolic disorder with profound loss of muscle and fat body mass resulting from a simultaneous reduction in protein synthesis and enhanced protein degradation. By contrast, retinal structure is largely maintained during diabetes despite reduced Akt activity and increased rate of cell death. Therefore, we hypothesized that retinal protein turnover is regulated differently than in other insulin-sensitive tissues, such as skeletal muscle. Ins2Akita diabetic mice and streptozotocin-induced diabetic rats exhibited marked reductions in retinal protein synthesis matched by a concomitant reduction in retinal protein degradation associated with preserved retinal mass and protein content. The reduction in protein synthesis depended on both hyperglycemia and insulin deficiency, but protein degradation was only reversed by normalization of hyperglycemia. The reduction in protein synthesis was associated with diminished protein translation efficiency but, surprisingly, not with reduced activity of the mTORC1/S6K1/4E-BP1 pathway. Instead, diabetes induced a specific reduction of mTORC2 complex activity. These findings reveal distinctive responses of diabetes-induced retinal protein turnover compared with muscle and liver that may provide a new means to ameliorate diabetic retinopathy.

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Section: Introductionmentioning

confidence: 99%

mTORC1-Independent Reduction of Retinal Protein Synthesis in Type 1 Diabetes

et al. 2014

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“…Therefore we have analysed coronary thrombus aspirates with one-dimensional PAGE followed by GeLC-MS/MS (tandem MS). Because of an altered synthesis and processing of many proteins in patients with diabetes [21], we excluded diabetic patients.…”

Section: Introductionmentioning

confidence: 99%

Proteomic profiling of acute coronary thrombosis reveals a local decrease in pigment epithelium-derived factor in acute myocardial infarction

et al. 2012

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Thrombotic occlusion of an epicardial coronary artery on the grounds of atherosclerotic plaque is considered the ultimate step in AMI (acute myocardial infarction). However, the precise pathophysiological mechanisms underlying acute coronary occlusion are not fully understood. We have analysed proteomic profiles of systemic plasma and plasma derived from the site of coronary plaque rupture of non-diabetic patients with STEMI (ST-segment elevation myocardial infarction). Label-free quantification of MS/MS (tandem MS) data revealed differential regulation of complement cascade components and a decrease in anti-thrombotic PEDF (pigment epithelium-derived factor) between CS (culprit site)-derived plasma and systemic plasma. PEDF, which is known to have a protective role in atherothrombosis, was relatively decreased at the CS, with a level of expression inverse to local MMP-9 (matrix metalloproteinase-9) activity. CS plasma displayed enhanced proteolytic activity towards PEDF. Proteomics of coronary thrombus aspirates indicate that PEDF processing is associated with coronary plaque rupture.

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“…All study volunteers were screened with a detailed medical history, physical exam, and hematological and biochemical profile (22–24). The list of medications taken by the participants is given in Supplementary Table 1.…”

Section: Methodsmentioning

confidence: 99%

Concordance of Changes in Metabolic Pathways Based on Plasma Metabolomics and Skeletal Muscle Transcriptomics in Type 1 Diabetes

et al. 2012

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Insulin regulates many cellular processes, but the full impact of insulin deficiency on cellular functions remains to be defined. Applying a mass spectrometry–based nontargeted metabolomics approach, we report here alterations of 330 plasma metabolites representing 33 metabolic pathways during an 8-h insulin deprivation in type 1 diabetic individuals. These pathways included those known to be affected by insulin such as glucose, amino acid and lipid metabolism, Krebs cycle, and immune responses and those hitherto unknown to be altered including prostaglandin, arachidonic acid, leukotrienes, neurotransmitters, nucleotides, and anti-inflammatory responses. A significant concordance of metabolome and skeletal muscle transcriptome–based pathways supports an assumption that plasma metabolites are chemical fingerprints of cellular events. Although insulin treatment normalized plasma glucose and many other metabolites, there were 71 metabolites and 24 pathways that differed between nondiabetes and insulin-treated type 1 diabetes. Confirmation of many known pathways altered by insulin using a single blood test offers confidence in the current approach. Future research needs to be focused on newly discovered pathways affected by insulin deficiency and systemic insulin treatment to determine whether they contribute to the high morbidity and mortality in T1D despite insulin treatment.

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Differential effects of insulin deprivation and systemic insulin treatment on plasma protein synthesis in type 1 diabetic people

Cited by 20 publications

References 34 publications

mTORC1-Independent Reduction of Retinal Protein Synthesis in Type 1 Diabetes

mTORC1-Independent Reduction of Retinal Protein Synthesis in Type 1 Diabetes

Proteomic profiling of acute coronary thrombosis reveals a local decrease in pigment epithelium-derived factor in acute myocardial infarction

Concordance of Changes in Metabolic Pathways Based on Plasma Metabolomics and Skeletal Muscle Transcriptomics in Type 1 Diabetes

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