Retinol Binding Protein 4: Role in Diabetes and Cancer

Berry, Daniel C.; Noy, Noa

doi:10.1007/978-3-319-41677-9_5

Cited by 5 publications

(5 citation statements)

References 104 publications

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“…Retinol-binding protein 4 (RBP4) protein belongs to the lipocalin family and is the specific carrier for retinol (vitamin A) in the blood [ 6 ]. It was reported that the level of circulating RBP4 is often elevated in obese mice and humans and that, under these circumstances, the protein induces insulin resistance [ 7 ]. Previous studies had suggested that circulating RBP4 levels were associated with insulin resistance [ 8 ], metabolic syndrome [ 9 ], impaired glucose tolerance [ 10 ], and type 2 diabetes [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Elevated RBP4 plasma levels were associated with diabetic retinopathy in type 2 diabetes

et al. 2018

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The retinol-binding protein 4 (RBP4) has been postulated to play a role in glucose homeostasis, insulin resistance, and diabetes mellitus in human and animal studies. The aim of the present study was to evaluate the role of RBP4 in Chinese patients with type 2 diabetes mellitus with and without diabetic retinopathy (DR). Plasma RBP4 concentrations were tested in 287 patients with type 2 diabetes. At baseline, demographic and clinical information including presence of DR and vision-threatening DR (VTDR) was collected. The relationship between RBP4 and DR (VTDR) was investigated using logistic regression. Patients with DR or VTDR had significantly higher plasma levels of RBP4 on admission (P<0.0001). Receiver operating characteristics (ROCs) to predict DR and VDTR demonstrated areas under the curve for RBP4 of 0.79 (95% confidence interval (CI): 0.73–0.85) and 0.90 (95% CI: 0.85–0.94), respectively, which were superior to other factors. For each 1 μg/ml increase in plasma level of RBP4, the unadjusted and adjusted risk of DR would be increased by 8% (with the odds ratio (OR) of 1.08 (95% CI: 1.05–1.13), P<0.001) and 5% (1.05 (1.02–1.11), P=0.001), respectively. It was 12% (with the OR of 1.12 (95% CI: 1.07–1.18), P<0.001) and 9% (1.09 (1.05–1.15), P<0.001) for VTDR. The present study shows that elevated plasma levels of RBP4 were associated with DR and VDTR in Chinese patients with type 2 diabetes, suggesting a possible role of RBP4 in the pathogenesis of DR complications. Lowering RBP4 could be a new strategy for treating type 2 diabetes with DR.

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Section: Introductionmentioning

confidence: 99%

Elevated RBP4 plasma levels were associated with diabetic retinopathy in type 2 diabetes

et al. 2018

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“…Retinol binding protein 4 (RBP4) is a 21‐kDa plasma protein that binds and transports Vitamin A (Retinol) in the blood . It is synthesized in multiple organs, including liver and adipose tissue where it is designated one of many adipokines . Circulating levels of RBP4 increase with obesity where they contribute to promotion of several obesity‐associated comorbidities, including cardiovascular , metabolic and neoplastic disorders .…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, RBP4 stimulates growth of established colorectal cancer (CRC) by binding and activating the membrane receptor STRA6 triggering downstream activation of the pro‐oncogenic JAK2/STAT3/5 pathway . Thus, RBP4 serves to promote cancer development and progression by a multi‐level cascade including direct activation of the JAK2 pathway and indirectly by stimulating insulin resistance and elevated insulin levels . Accordingly, since RBP4 contributes to the linkage between obesity and several of its comorbidities, including type 2 diabetes mellitus, coronary artery disease (CAD), and cancer, it is important to determine factors affecting circulating levels including the importance of gender and age.…”

Section: Introductionmentioning

confidence: 99%

Sexual dimorphism in developmental and diet‐dependent circulating retinol binding protein 4

Bakshi

Schmidt

Baskin

et al. 2018

Obesity Science & Practice

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SummaryObjectiveRetinol binding protein 4 (RBP4) transports vitamin A (Retinol) in the blood and contributes mechanistically to the linkage between obesity, insulin resistance and associated comorbidities including type 2 diabetes mellitus, coronary artery and neoplastic diseases. Circulating RBP4 levels have variably been associated with body mass and gender differences. Many of these differences have been demonstrated after limited dietary interventions, and/or at single unique time points. This study investigated the impact of sex and age as biologic variables as well as high versus low fat diets on development of obesity, RBP4 levels and insulin resistance in C57BL/6J mice.MethodsMale and female C57BL/6J mice were fed for 400 days with either low or high fat diets. Female mice were also evaluated on same diets after ovariectomy or sham ovariectomy. Mice were monitored for changes in weight, circulating levels RBP4, glucose and insulin at 100‐day intervals and also by 2‐hour glucose tolerance tests.ResultsAll mice on low or high fat diets gained weight. Mice on high fat diets showed significantly greater weight gain than those on low fat. Male mice showed significantly greater weight gain compared with females on corresponding diet. Male mice compared with females already showed significantly higher RBP4 levels even before starting diets. Sex differences were maintained for more than 1 year. Gender differences in RBP4 were associated with significant differences in development of glucose intolerance and insulin resistance.ConclusionsMale compared with female C57BL/6J mice show significant gender differences in circulating RBP4 levels from 6 weeks of age, extending more than 1 year. Gender differences in RBP4 may be mechanistically associated with protection against glucose intolerance and insulin resistance. Targeting RBP4 pathways could be useful to disrupt gender differences in insulin resistance and disparities in comorbidities.

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“…Type 2 diabetes mellitus and insulin resistance are linked to RBP4 levels in the blood (Sun et al, 2014). An elevated level of RBP4 induces insulin resistance (Berry et al, 2017) and upregulated expression of PEPCK (Tamori et al, 2006). RBP4, triglycerides, and insulin resistance all had a close relationship (Graham et al, 2006;Vergès et al, 2012;Rocha et al, 2013).…”

Section: Introductionmentioning

confidence: 97%

The Effects of Soyferment-Tempeh on Lipid Profile, Retinol-Binding Protein 4 (RBP4), and Phosphoenolpyruvate Carboxykinase (PEPCK) Gene Expression in Type 2 Diabetic Mice

Prasetyastuti

Ghozali

2021

Indonesian J Pharm

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Diabetes Type 2 can cause oxidative stress leading to the accumulation of reactive oxygen species. Soyferment-Tempeh, a fermented soybean product with aerobic and anaerobic R. oligosporus incubation has a high antioxidant content of isoflavones that can regulate oxidative stress in diabetes. In this study, we evaluate the effects of Soyferment-Tempeh on lipid profile, Retinol-Binding Protein 4 (RBP4), and Phosphoenolpyruvate Carboxykinase (PEPCK) gene expression in type 2 diabetic mice. A total of 30 mice with the age of eight weeks were divided into six groups as follows: A) nondiabetic, B) diabetic mice, C) diabetic mice with metformin, D), E), and F) diabetic mice with Soyferment-Tempeh doses of 10, 20, or 40mg/100g body weight (BW), respectively, were administered treatments orally by gavages. Blood was collected for assessment of blood glucose level, and lipid profile before and after 3 weeks of the administration. After sacrificing the mice, livers were used for RBP4 and PEPCK gene expression assessment. Supplementation with three different doses of Soyferment-Tempeh in streptozotocin-induced diabetic mice for 21 days significantly (p<0.001) reduced blood glucose level, total cholesterol, triglycerides, low-density lipoprotein level, atherogenic index, and increased high-density lipoprotein level. There was a significant decrease in RBP4 gene expression in the Soyferment-Tempeh of dose 10mg/100g BW treatment groups (p<0.05), while the PEPCK gene expression did not significantly differ (p>0.05). These results demonstrate that supplementation with Soyferment-Tempeh decreases blood glucose level, atherogenic index, improves lipid profile, and decreases RBP4.

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Retinol Binding Protein 4: Role in Diabetes and Cancer

Cited by 5 publications

References 104 publications

Elevated RBP4 plasma levels were associated with diabetic retinopathy in type 2 diabetes

Elevated RBP4 plasma levels were associated with diabetic retinopathy in type 2 diabetes

Sexual dimorphism in developmental and diet‐dependent circulating retinol binding protein 4

The Effects of Soyferment-Tempeh on Lipid Profile, Retinol-Binding Protein 4 (RBP4), and Phosphoenolpyruvate Carboxykinase (PEPCK) Gene Expression in Type 2 Diabetic Mice

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