Serum vitamin A and retinol-binding protein in patients with insulin-dependent diabetes mellitus

Basu, Tapan K.; Tze, Wah Jun; Leichter, Joseph

doi:10.1093/ajcn/50.2.329

Cited by 85 publications

(77 citation statements)

References 18 publications

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“…This is further supported by the observation that retinyl ester hydrolase activity in liver was found to be decreased in T1D rat models, but not in intestine, in agreement with increased hepatic accumulation without changes in the intestinal absorption of retinol (51). It is also possible that the decrease in plasma retinol and/or RBP4 could be a result of increased renal filtration due to low plasma TTR concentrations during T1D (40,41). It has been reported that plasma TTR concentrations were depressed in newly diagnosed T1D human subjects as well as in T1D rat models (29,32,41).…”

Section: Plasma Rbp4 Ttr and Retinol Levels In Type 1 Diabetessupporting

confidence: 56%

“…Furthermore, the low retinol phenotype also appears to be heritable among T1D subjects, suggesting an inherent metabolic link between T1D and vitamin A transport. Basu et al (40,41) also reported declined plasma vitamin A levels in T1D adults. Interestingly, plasma levels of vitamin A in diabetic patients as well as in the control subjects showed a significant linear regression with plasma concentrations of RBP4, suggesting incomplete mobilization from liver stores or increased renal clearance of RBP4 (40,41).…”

Section: Plasma Rbp4 Ttr and Retinol Levels In Type 1 Diabetesmentioning

confidence: 92%

“…Basu et al (40,41) also reported declined plasma vitamin A levels in T1D adults. Interestingly, plasma levels of vitamin A in diabetic patients as well as in the control subjects showed a significant linear regression with plasma concentrations of RBP4, suggesting incomplete mobilization from liver stores or increased renal clearance of RBP4 (40,41). However, in these subjects, the plasma vitamin E concentrations remained normal, implying specific alterations in the vitamin A transport during T1D (40).…”

Section: Plasma Rbp4 Ttr and Retinol Levels In Type 1 Diabetesmentioning

confidence: 92%

“…Although plasma retinol and RBP4 levels in plasma of T1D subjects are reduced when compared with their normal counterparts, it did not manifest subclinical vitamin A deficiency (40,41). Alternatively, urinary excretion of both RBP4 and retinol was found to be elevated in T1D subjects even under conditions of normoalbuminurea (45,46), suggesting that increased renal filtration might also account for reduced plasma RBP4/retinol levels ( Fig.…”

Section: Plasma Rbp4 Ttr and Retinol Levels In Type 1 Diabetesmentioning

confidence: 94%

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Contrasting effects of type 2 and type 1 diabetes on plasma RBP4 levels: The significance of transthyretin

et al. 2012

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SummaryRetinol-binding protein 4 (RBP4) is the principle carrier of retinol in the human plasma, which circulates as a complex with transthyretin (TTR), a homotetrameric thyroxine transport protein. Although this complex formation is thought to prevent glomerular filtration of RBP4, it also stabilizes the quaternary structure of TTR. Recent studies indicate elevated plasma levels of RBP4 in type 2 diabetes (T2D). In contrast, reduced RBP4 levels were observed in type 1 diabetes (T1D). Herein, we critically examine the probable mechanisms involved in the regulation of RBP4 and TTR levels during T2D and T1D. The available evidences point to the involvement of pancreatic factors in regulating the expression of both RBP4 and TTR. It appears that during T1D, TTR levels are reduced and it exists predominantly as a monomer that may interfere its interaction with RBP4 resulting in its loss through glomerular filtration. However, plasma TTR levels remain high under T2D conditions and thus reducing glomerular filtration of RBP4. Therefore, the plasma TTR levels appear to be an important determinant of plasma RBP4 levels in these two diabetic conditions. 2012 IUBMB IUBMB Life, 64(12): 975-982, 2012

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Section: Plasma Rbp4 Ttr and Retinol Levels In Type 1 Diabetessupporting

confidence: 56%

Section: Plasma Rbp4 Ttr and Retinol Levels In Type 1 Diabetesmentioning

confidence: 92%

Section: Plasma Rbp4 Ttr and Retinol Levels In Type 1 Diabetesmentioning

confidence: 92%

Section: Plasma Rbp4 Ttr and Retinol Levels In Type 1 Diabetesmentioning

confidence: 94%

See 2 more Smart Citations

Contrasting effects of type 2 and type 1 diabetes on plasma RBP4 levels: The significance of transthyretin

et al. 2012

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“…Several studies have reported that serum levels of both carotene and vitamin A are within normal range in diabetes mellitus (Murrill et al, 1941;Kimble et al, 1946;Ramachandran, 1973). Recently, an increase in plasma retinyl esters has been reported in Type 2 diabetes (Wako et al, 1986) and a decrease in serum concentration of vitamin A and RBP in Type 1 diabetes (Basu et al, 1989). Other investigators found that retinol concentrations were signi®cantly decreased in Type 1 (Krempf et al, 1991) and increased in Type 2 diabetes mellitus as compared to control subjects (Krempf et al, 1991;Havivi et al, 1991;Sasaki et al, 1995).…”

Section: Introductionmentioning

confidence: 97%

Retinol, α-tocopherol and carotenoids in diabetes

et al. 1999

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Objective: A case-control study was conducted to evaluate the effects of diabetes mellitus on serum levels of vitamin A, a-carotene, b-carotene, a-tocopherol, serum and urine RBP. Subjects: One hundred and seven patients with Type 2 diabetes mellitus (28 ± 74 y) were recruited from those attending a primary health care clinic in King Khalid University Hospital in Riyadh City (Saudi Arabia). They were matched for age and sex with 143 healthy individuals. Methods: Fasting blood samples and 10 h urine collections were obtained from all subjects. Levels of vitamins and carotenoids in serum measured by high performance liquid chromatography (HPLC), and of retinol binding protein (RBP) in serum and urine by an enzyme-linked immunosorbent assay (ELISA). Results: The mean serum concentrations of retinol, a-carotene, and a-tocopherol were similar in both groups after correction of lipid soluble vitamins for serum lipids levels. However, serum b-carotene concentration was signi®cantly higher in control subjects than diabetics (P 0.002). Serum and urine RBP concentrations were signi®cantly higher in diabetics than in controls (P 0.0001 ). In normal subjects (but not diabetics) serum concentrations of retinol and RBP were higher in men than in women (P 0.02, P 0.0001 respectively). In both normal and diabetic subjects, serum levels of a-tocopherol (P 0.007) and urine RBP (P 0.005), were higher in men than women. Urinary excretion of RBP was signi®cantly higher in diabetic patients with renal impairment than other diabetics or controls (P 0.0001). There was a negative correlation between fasting blood glucose (FBG) concentration and serum b-carotene (P 0.008) in the total combined group and a positive correlation between FBG and urinary RBPacreatinine (P 0.009) in diabetic patients. Conclusion: Serum b-carotene concentration was signi®cantly lower in diabetic patients than controls. Serum retinol concentration in patients with diabetes was normal, yet serum and urine RBP concentrations were signi®cantly higher in diabetics than in controls. Sponsorship: The research was sponsored by King Faisal Specialist Hospital and Research Center.

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High Glucose‐induced repression of RAR/RXR in cardiomyocytes is mediated through oxidative stress/JNK signaling

Singh

Guleria

Nizamutdinova

et al. 2012

Journal Cellular Physiology

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The biological actions of retinoids are mediated by nuclear retinoic acid receptors (RARs) and retinoid × receptors (RXRs). We have recently reported that decreased expression of RARα and RXRα has an important role in high glucose (HG)-induced cardiomyocyte apoptosis. However, the regulatory mechanisms of HG effects on RARα and RXRα remain unclear. Using neonatal cardiomyocytes, we found that ligand-induced promoter activity of RAR and RXR was significantly suppressed by HG. HG promoted protein destabilization and serine-phosphorylation of RARα and RXRα. Proteasome inhibitor MG132 blocked the inhibitory effect of HG on RARα and RXRα. Inhibition of intracellular reactive oxidative species (ROS) abolished the HG effect. In contrast, H2O2 stimulation suppressed the expression and ligand-induced promoter activity of RARα and RXRα. HG promoted phosphorylation of ERK1/2, JNK and p38 MAP kinases, which was abrogated by an ROS inhibitor. Inhibition of JNK, but not ERK and p38 activity, reversed HG effects on RARα and RXRα. Activation of JNK by over expressing MKK7 and MEKK1, resulted in significant downregulation of RARα and RXRα. Ligand-induced promoter activity of RARα and RXRα was also suppressed by overexpression of MEKK1. HG-induced cardiomyocyte apoptosis was potentiated by activation of JNK, and prevented by ATRA and inhibition of JNK. Silencing the expression of RARα and RXRα activated the JNK pathway. In conclusion, HG-induced oxidative stress and activation of the JNK pathway negatively regulated expression/activation of RAR and RXR. The impaired RAR/RXR signaling and oxidative stress/JNK pathway forms a vicious circle, which significantly contributes to hyperglycemia induced cardiomyocyte apoptosis.

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Serum vitamin A and retinol-binding protein in patients with insulin-dependent diabetes mellitus

Cited by 85 publications

References 18 publications

Contrasting effects of type 2 and type 1 diabetes on plasma RBP4 levels: The significance of transthyretin

Contrasting effects of type 2 and type 1 diabetes on plasma RBP4 levels: The significance of transthyretin

Retinol, α-tocopherol and carotenoids in diabetes

High Glucose‐induced repression of RAR/RXR in cardiomyocytes is mediated through oxidative stress/JNK signaling

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