A novel truncated form of apolipoprotein A-I transported by dense LDL is increased in diabetic patients

Cubedo, Judit; Padró, Teresa; García-Arguinzonis, Maisa; Vilahur, Gemma; Miñambres, Inka; Pou, J. M.; Ybarra, Juan; Badimon, Lina

doi:10.1194/jlr.p057513

Cited by 13 publications

(14 citation statements)

References 54 publications

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“…It has been suggested that CSTD acts a mediator between obesity and chronic adipose tissue inflammation as weight gain has shown to stimulate CTSD activity leading to adipocyte apoptosis, which is an important contributor to insulin resistance 25 . Furthermore, increased CTSD activity has in experimental studies been shown to be involved in the truncation of ApoA1 (the most abundant protein in HDL) to ApoA1Δ(1–38); a variant which is more abundant in patients with diabetes and more susceptible to oxidation 26 .…”

Section: Discussionmentioning

confidence: 99%

Using a Targeted Proteomics Chip to Explore Pathophysiological Pathways for Incident Diabetes– The Malmö Preventive Project

Molvin

Pareek

Jujić

et al. 2019

Sci Rep

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Multiplex proteomic platforms provide excellent tools for investigating associations between multiple proteins and disease (e.g., diabetes) with possible prognostic, diagnostic, and therapeutic implications. In this study our aim was to explore novel pathophysiological pathways by examining 92 proteins and their association with incident diabetes in a population-based cohort (146 cases of diabetes versus 880 controls) followed over 8 years. After adjusting for traditional risk factors, we identified seven proteins associated with incident diabetes. Four proteins (Scavenger receptor cysteine rich type 1 protein M130, Fatty acid binding protein 4, Plasminogen activator inhibitor 1 and Insulin-like growth factor-binding protein 2) with a previously established association with incident diabetes and 3 proteins (Cathepsin D, Galectin-4, Paraoxonase type 3) with a novel association with incident diabetes. Galectin-4, with an increased risk of diabetes, and Paraoxonase type 3, with a decreased risk of diabetes, remained significantly associated with incident diabetes after adjusting for plasma glucose, implying a glucose independent association with diabetes.

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Section: Discussionmentioning

confidence: 99%

Using a Targeted Proteomics Chip to Explore Pathophysiological Pathways for Incident Diabetes– The Malmö Preventive Project

Molvin

Pareek

Jujić

et al. 2019

Sci Rep

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“…Analysis for differences in the protein profiles was performed with the PD-Quest 8.0 software (BioRad, Hercules, CA, USA). Each spot was assigned a relative value that corresponds to the single spot volume compared to the volume of all the spots in the gel, following background extraction and normalization between gels [ 26 ].…”

Section: Methodsmentioning

confidence: 99%

Effects of a Carob-Pod-Derived Sweetener on Glucose Metabolism

et al. 2018

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Background: Patients with type 2 diabetes mellitus (T2DM) have a higher incidence of cardiovascular (CV) events. The ingestion of high-glycemic index (GI) diets, specially sweetened beverage consumption, has been associated with the development of T2DM and CV disease. Objective: We investigated the effects of the intake of a sweetened beverage, obtained from natural carbohydrates containing pinitol (PEB) compared to a sucrose-enriched beverage (SEB) in the context of impaired glucose tolerance (IGT) and diabetes. Methods: The study was divided in three different phases: (1) a discovery phase where the plasma proteomic profile was investigated by 2-DE (two-dimensional electrophoresis) followed by mass spectrometry (matrix-assisted laser desorption/ionization time-of-flight—MALDI-TOF/TOF) in healthy and IGT volunteers; (2) a verification phase where the potential mechanisms behind the observed protein changes were investigated in the discovery cohort and in an additional group of T2DM volunteers; and (3) the results were validated in a proof-of-concept interventional study in an animal model of diabetic rats with complementary methodologies. Results: Six weeks of pinitol-enriched beverage (PEB) intake induced a significant increase in two proteins involved in the insulin secretion pathway, insulin-like growth factor acid labile subunit (IGF1BP-ALS; 1.3-fold increase; P = 0.200) and complement C4A (1.83-fold increase; P = 0.007) in IGT subjects but not in healthy volunteers. Changes in C4A were also found in the serum samples of Zucker diabetic fatty (ZDF) rats after four weeks of PEB intake compared to basal levels (P = 0.042). In addition, an increased expression of the glucose transporter-2 (GLUT2) gene was observed in the jejunum (P = 0.003) of inositol-supplemented rats when compared to sucrose supplementation. This change was correlated with the observed change in C4A (P = 0.002). Conclusions: Our results suggest that the substitution of a common sugar source, such as sucrose, by a naturally-based, pinitol-enriched beverage induces changes in the insulin secretion pathway that could help to reduce blood glucose levels by protecting β-cells and by stimulating the insulin secretion pathway. This mechanism of action could have a relevant role in the prevention of insulin resistance and diabetes progression.

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“…Furthermore, in patients with diabetes, CTSD has been shown to truncate ApoA1 (the main protein of HDL) to ApoA1Δ (1-38), which binds to low-density lipoprotein and increases its susceptibility to oxidation, possibly contributing to the increased risk of CVD in diabetes. 31 In the setting of an acute coronary syndrome (ACS), previous studies of CTSD are somewhat conflicting. Vivanco et al used a proteomic approach to demonstrate that CTSD was significantly higher in the plasma of ACS patients as compared with healthy subjects.…”

Section: Proteins With a Novel Association With Cardiovascular Outcommentioning

confidence: 99%

Proteomic exploration of common pathophysiological pathways in diabetes and cardiovascular disease

et al. 2020

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Aims The epidemiological association between diabetes and cardiovascular disease is well established, but the pathophysiological link is complex and multifactorial. We investigated seven proteins, previously linked to incident diabetes mellitus, and their association with cardiovascular disease and mortality. Methods and results Plasma samples from 1713 individuals from the Swedish population-based Malmö Preventive Project (mean age 67.4 ± 6.0 years; 29.1% women) were analysed with a proximity extension assay panel. Seven proteins [scavenger receptor cysteine rich type 1 protein M130 (CD163), fatty acid-binding protein 4 (FABP4), plasminogen activator inhibitor 1 (PAI), insulin-like growth factor-binding protein 2 (IGFB2), cathepsin D (CTSD), galectin-4 (GAL4), and paraoxonase-3 (PON3)] previously shown to be associated with incident diabetes were analysed for associations with all-cause mortality (ACM), cardiovascular mortality (CVM), incident coronary events (CEs), and incident heart failure (HF). After exclusion of prevalent cases of respective outcome, proteins that met Bonferroni-corrected significance were analysed in multivariable Cox regression models. Significant associations were identified between five proteins [GAL4 (hazard ratio; 95% confidence interval:

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A novel truncated form of apolipoprotein A-I transported by dense LDL is increased in diabetic patients

Cited by 13 publications

References 54 publications

Using a Targeted Proteomics Chip to Explore Pathophysiological Pathways for Incident Diabetes– The Malmö Preventive Project

Using a Targeted Proteomics Chip to Explore Pathophysiological Pathways for Incident Diabetes– The Malmö Preventive Project

Effects of a Carob-Pod-Derived Sweetener on Glucose Metabolism

Proteomic exploration of common pathophysiological pathways in diabetes and cardiovascular disease

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