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The origin of circulating CD36 in type 2 diabetes.

Alkhatatbeh MJ, Enjeti AK, Acharya S, Thorne RF, Lincz LF - Nutr Diabetes (2013)

Bottom Line: CD36+MP levels were significantly higher in obese people with T2DM (P<0.00001) and were primarily derived from erythrocytes (CD235a+=35.8±14.6%); although this did not correlate with haemoglobin A(1c).Across the entire cohort, plasma CD36 protein concentration varied from undetectable to 22.9 μg ml(-1) and was positively correlated with CD36+MPs measured by flow cytometry (P=0.0006) but only weakly associated with the distribution of controls and T2DM (P=0.021).Multivariate analysis confirmed that plasma CD36+MP levels were a much better biomarker for diabetes than CD36 protein concentration (P=0.009 vs P=0.398, respectively).

View Article: PubMed Central - PubMed

Affiliation: 1] Cancer Research Unit, School of Biomedical Sciences and Pharmacy, Faculty of Health, the University of Newcastle, Newcastle, NSW, Australia [2] Hunter Medical Research Institute, New Lambton, NSW, Australia.

ABSTRACT

Objective: Elevated plasma levels of the fatty acid transporter, CD36, have been shown to constitute a novel biomarker for type 2 diabetes mellitus (T2DM). We recently reported such circulating CD36 to be entirely associated with cellular microparticles (MPs) and aim here to determine the absolute levels and cellular origin(s) of these CD36+MPs in persons with T2DM.

Design: An ex vivo case-control study was conducted using plasma samples from 33 obese individuals with T2DM (body mass index (BMI)=39.9±6.4 kg m(-2); age=57±9 years; 18 male:15 female) and age- and gender-matched lean and obese non-T2DM controls (BMI=23.6±1.8 kg m(-2) and 33.5±5.9 kg m(-2), respectively). Flow cytometry was used to analyse surface expression of CD36 together with tissue-specific markers: CD41, CD235a, CD14, CD105 and phosphatidyl serine on plasma MPs. An enzyme-linked immunosorbent assay was used to quantify absolute CD36 protein concentrations.

Results: CD36+MP levels were significantly higher in obese people with T2DM (P<0.00001) and were primarily derived from erythrocytes (CD235a+=35.8±14.6%); although this did not correlate with haemoglobin A(1c). By contrast, the main source of CD36+MPs in non-T2DM individuals was endothelial cells (CD105+=40.9±8.3% and 33.9±8.3% for lean and obese controls, respectively). Across the entire cohort, plasma CD36 protein concentration varied from undetectable to 22.9 μg ml(-1) and was positively correlated with CD36+MPs measured by flow cytometry (P=0.0006) but only weakly associated with the distribution of controls and T2DM (P=0.021). Multivariate analysis confirmed that plasma CD36+MP levels were a much better biomarker for diabetes than CD36 protein concentration (P=0.009 vs P=0.398, respectively).

Conclusions: Both the levels and cellular profile of CD36+MPs differ in T2DM compared with controls, suggesting that these specific vesicles could represent distinct biological vectors contributing to the pathology of the disease.

No MeSH data available.


Related in: MedlinePlus

Quartiles of plasma CD36 protein concentration measured by ELISA compared with numbers of circulating CD36+MPs measured by flow cytometry in lean controls, obese controls and obese T2DM individuals.
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fig5: Quartiles of plasma CD36 protein concentration measured by ELISA compared with numbers of circulating CD36+MPs measured by flow cytometry in lean controls, obese controls and obese T2DM individuals.

Mentions: An ELISA assay was devised to measure the absolute levels of CD36 protein in the same plasma samples used in the above experiments. These levels were determined to range from undetectable in 31/99 participants to as high as 22.9 μg ml−1. As shown in Figure 4, the median levels progressively increased from lean to obese controls to obese diabetic individuals (1.71 vs 2.47 vs 3.90 μg ml−1), with the difference between the latter two cohorts being statistically significant (P=0.036). In order to accurately assess the relationship between protein and MP levels of CD36, the CD36 protein concentrations were log transformed and divided into quartiles to accommodate the large number of data points below the limit of detection for the assay. This was then compared with the normalised CD36+MP levels for each lean, obese and obese diabetic participant, with the results illustrated in Figure 5. When all cohorts were combined, it became clear that there was a strong correlation between CD36+MP levels and CD36 protein concentrations (P=0.0006). However, the individual distributions of lean, obese and obese diabetic participants was only weakly correlated with quartiles of plasma CD36 protein concentration (P=0.021), with diabetic patients appearing in all the quartiles. By contrast, none of the diabetic patients had CD36+MP levels in the lower half of the y axis as illustrated on the graph. Multivariate analysis confirmed that even when corrected for BMI and blood parameters, CD36+MP levels were a much better marker of diabetes than CD36 protein levels (P=0.009 vs P=0.398, respectively). However, neither parameter was significantly associated with obesity in the control cohorts (P=0.173 for CD36+MP and P=0.906 for quartiles of CD36 protein levels).


The origin of circulating CD36 in type 2 diabetes.

Alkhatatbeh MJ, Enjeti AK, Acharya S, Thorne RF, Lincz LF - Nutr Diabetes (2013)

Quartiles of plasma CD36 protein concentration measured by ELISA compared with numbers of circulating CD36+MPs measured by flow cytometry in lean controls, obese controls and obese T2DM individuals.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3584987&req=5

fig5: Quartiles of plasma CD36 protein concentration measured by ELISA compared with numbers of circulating CD36+MPs measured by flow cytometry in lean controls, obese controls and obese T2DM individuals.
Mentions: An ELISA assay was devised to measure the absolute levels of CD36 protein in the same plasma samples used in the above experiments. These levels were determined to range from undetectable in 31/99 participants to as high as 22.9 μg ml−1. As shown in Figure 4, the median levels progressively increased from lean to obese controls to obese diabetic individuals (1.71 vs 2.47 vs 3.90 μg ml−1), with the difference between the latter two cohorts being statistically significant (P=0.036). In order to accurately assess the relationship between protein and MP levels of CD36, the CD36 protein concentrations were log transformed and divided into quartiles to accommodate the large number of data points below the limit of detection for the assay. This was then compared with the normalised CD36+MP levels for each lean, obese and obese diabetic participant, with the results illustrated in Figure 5. When all cohorts were combined, it became clear that there was a strong correlation between CD36+MP levels and CD36 protein concentrations (P=0.0006). However, the individual distributions of lean, obese and obese diabetic participants was only weakly correlated with quartiles of plasma CD36 protein concentration (P=0.021), with diabetic patients appearing in all the quartiles. By contrast, none of the diabetic patients had CD36+MP levels in the lower half of the y axis as illustrated on the graph. Multivariate analysis confirmed that even when corrected for BMI and blood parameters, CD36+MP levels were a much better marker of diabetes than CD36 protein levels (P=0.009 vs P=0.398, respectively). However, neither parameter was significantly associated with obesity in the control cohorts (P=0.173 for CD36+MP and P=0.906 for quartiles of CD36 protein levels).

Bottom Line: CD36+MP levels were significantly higher in obese people with T2DM (P<0.00001) and were primarily derived from erythrocytes (CD235a+=35.8±14.6%); although this did not correlate with haemoglobin A(1c).Across the entire cohort, plasma CD36 protein concentration varied from undetectable to 22.9 μg ml(-1) and was positively correlated with CD36+MPs measured by flow cytometry (P=0.0006) but only weakly associated with the distribution of controls and T2DM (P=0.021).Multivariate analysis confirmed that plasma CD36+MP levels were a much better biomarker for diabetes than CD36 protein concentration (P=0.009 vs P=0.398, respectively).

View Article: PubMed Central - PubMed

Affiliation: 1] Cancer Research Unit, School of Biomedical Sciences and Pharmacy, Faculty of Health, the University of Newcastle, Newcastle, NSW, Australia [2] Hunter Medical Research Institute, New Lambton, NSW, Australia.

ABSTRACT

Objective: Elevated plasma levels of the fatty acid transporter, CD36, have been shown to constitute a novel biomarker for type 2 diabetes mellitus (T2DM). We recently reported such circulating CD36 to be entirely associated with cellular microparticles (MPs) and aim here to determine the absolute levels and cellular origin(s) of these CD36+MPs in persons with T2DM.

Design: An ex vivo case-control study was conducted using plasma samples from 33 obese individuals with T2DM (body mass index (BMI)=39.9±6.4 kg m(-2); age=57±9 years; 18 male:15 female) and age- and gender-matched lean and obese non-T2DM controls (BMI=23.6±1.8 kg m(-2) and 33.5±5.9 kg m(-2), respectively). Flow cytometry was used to analyse surface expression of CD36 together with tissue-specific markers: CD41, CD235a, CD14, CD105 and phosphatidyl serine on plasma MPs. An enzyme-linked immunosorbent assay was used to quantify absolute CD36 protein concentrations.

Results: CD36+MP levels were significantly higher in obese people with T2DM (P<0.00001) and were primarily derived from erythrocytes (CD235a+=35.8±14.6%); although this did not correlate with haemoglobin A(1c). By contrast, the main source of CD36+MPs in non-T2DM individuals was endothelial cells (CD105+=40.9±8.3% and 33.9±8.3% for lean and obese controls, respectively). Across the entire cohort, plasma CD36 protein concentration varied from undetectable to 22.9 μg ml(-1) and was positively correlated with CD36+MPs measured by flow cytometry (P=0.0006) but only weakly associated with the distribution of controls and T2DM (P=0.021). Multivariate analysis confirmed that plasma CD36+MP levels were a much better biomarker for diabetes than CD36 protein concentration (P=0.009 vs P=0.398, respectively).

Conclusions: Both the levels and cellular profile of CD36+MPs differ in T2DM compared with controls, suggesting that these specific vesicles could represent distinct biological vectors contributing to the pathology of the disease.

No MeSH data available.


Related in: MedlinePlus