Vitamin A in regulation of insulin responsiveness: mini review

Vitamin A, retinol, circulates in blood bound to retinol-binding protein (RBP4) which, in turn, associates with another serum protein, transthyretin (TTR), to form a ternary retinol-RBP4-TTR complex. At some tissues, retinol-bound (holo-) RBP4 is recognised by a receptor termed stimulated by retinoic acid 6 (STRA6) which transports retinol into cells. This mini-review summarises evidence demonstrating that, in addition to functioning as a retinol transporter, STRA6 is also a signalling receptor which is activated by holo-RBP4. The data show that STRA6-mediated retinol transport induces receptor phosphorylation, in turn activating a Janus kinases2/signal transducers and activators of transcription (STAT)3/5 cascade that culminates in induction of STAT target genes. STRA6-mediated retinol transport and cell signalling are inter-dependent, and both functions critically rely on intracellular retinol trafficking and metabolism. Hence, STRA6 couples ‘sensing’ of vitamin A homeostasis and metabolism to cell signalling, allowing it to control important biological functions. For example, by inducing the expression of the STAT target gene suppressor of cytokine signalling 3, STRA6 potently suppresses insulin responses. These observations provide a rationale for understanding the reports that elevation in serum levels of RBP4, often observed in obese mice and human subjects, causes insulin resistance. The observations indicate that the holo-RBP4 /STRA6 signalling cascade may comprise an important link through which obesity leads to insulin resistance and suggest that the pathway may be a novel target for treatment of metabolic diseases.

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Effects of 10-Week Concurrent Training on Insulin Resistance and the Serum Levels of Vaspin and Visfatin in Overweight Females

Quarterly of Horizon of Medical Sciences ◽

10.32598/hms.25.3.146 ◽

2019 ◽

Vol 25 (3) ◽

pp. 146-157

Author(s):

Abdolreza Kazemi ◽

◽

Sareh Mahalati ◽

Keyword(s):

Insulin Resistance ◽

Metabolic Diseases ◽

Intervention Group ◽

Serum Levels ◽

Analysis Of Covariance ◽

Concurrent Training ◽

Improve Insulin Sensitivity ◽

Glucose Levels ◽

Kerman City ◽

Training Protocol

Aims: The present study investigated the effects of a 10-week concurrent training on the serum levels of vaspin and visfatin in overweight females. Methods & Materials: Twenty-four over-weight females from Kerman City, Iran (Mean±SD age: 11.23±0.62 years; Mean±SD weight: 64.83±2.70kg; Mean±SD BMI: 27.97±0.47 kg/m2) were randomly assigned into the control and concurrent training groups. The intervention group performed the training protocol as follows: endurance training: 65-85% of Vo2 max for 20 minutes per session, and resistance training: 50-60% of One Repetition Maximum (1RM) for 30 minutes per session and 3 days a week for 10 weeks. Fasting plasma vaspin, visfatin, and insulin levels were measured by ELISA method. To analyze the data, Analysis of Covariance (ANCOVA) was used. Findings: Performing 10 weeks of concurrent training significantly decreased vaspin and visfatin plasma levels, and insulin resistance resting levels (P≤0.05); however, there was no significant decrease in glucose levels. Conclusion: Concurrent training can decrease insulin resistance, probably by reducing vaspin and visfatin in overweight females. Therefore, it is suggested that overweight females use concurrent training to improve insulin sensitivity and prevent metabolic diseases.

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RBP4: A Culprit for Insulin Resistance in End Stage Renal Disease That Can Be Cleared by Hemodiafiltration

BioMed Research International ◽

10.1155/2017/7270595 ◽

2017 ◽

Vol 2017 ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

Fabrizio Grosjean ◽

Pasquale Esposito ◽

Rosario Maccarrone ◽

Carmelo Libetta ◽

Antonio Dal Canton ◽

...

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Kidney Transplant ◽

Glucose Transporter ◽

Serum Levels ◽

Tissue Expression ◽

Serum Glucose ◽

Retinol Binding Protein ◽

Retinol Binding Protein 4 ◽

Glut4 Expression

Introduction. Retinol Binding Protein 4 (RBP4) is mainly excreted by the kidney and plays a pivotal role in insulin resistance (IR). In our study, we evaluated the association between RBP4 and IR in hemodialysis subjects (HD). We also assessed how circulating RBP4 could be influenced by kidney transplant or different dialytic techniques.Methods. RBP4 serum levels were evaluated in HD (n=16) and matched healthy controls (C;n=16). RBP4 and glucose transporter type 4 (GLUT4) mRNA expressions were also determined in adipose tissue. Circulating RBP4 was evaluated after kidney transplant (n=7) and in hemodialysis patients (n=10) enrolled in a cross-over study treated with standard bicarbonate dialysis (BD) or hemodiafiltration (HDF).Results. HOMA index (P<0.05) and serum RBP4 (P<0.005) were higher in HD compared to C. RBP4 levels positively correlated with fasting serum glucose (P<0.05). RBP4 mRNA was lower in HD compared to C (P<0.05) and positively correlated with kidney function (P<0.05) and GLUT4 mRNA (P<0.001). Transplant or HDF reduced circulating RBP4 (P<0.01andP<0.05, resp.). Our results demonstrate that IR is associated with high circulating RBP4 and that suppressed RBP4 adipose tissue expression is accompanied by reduced GLUT4 expression in HD. Renal transplantation or HDF are effective in lowering serum RBP4 levels.

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Ghrelin- and GH-induced insulin resistance: no association with retinol-binding protein-4

Endocrine Connections ◽

10.1530/ec-13-0019 ◽

2013 ◽

Vol 2 (2) ◽

pp. 96-103 ◽

Cited By ~ 2

Author(s):

Esben Thyssen Vestergaard ◽

Morten B Krag ◽

Morten M Poulsen ◽

Steen B Pedersen ◽

Niels Moller ◽

...

Keyword(s):

Insulin Resistance ◽

Insulin Sensitivity ◽

Binding Protein ◽

Human Subjects ◽

Retinol Binding Protein ◽

Double Blind ◽

Double Blind Placebo ◽

Retinol Binding Protein 4 ◽

Euglycemic Clamp ◽

Hyperinsulinemic Euglycemic Clamp

ObjectiveSupraphysiological levels of ghrelin and GH induce insulin resistance. Serum levels of retinol-binding protein-4 (RBP4) correlate inversely with insulin sensitivity in patients with type 2 diabetes. We aimed to determine whether ghrelin and GH affect RBP4 levels in human subjects.Materials and methodsTo study GH-independent effects of ghrelin, seven hypopituitary men undergoing replacement therapy with GH and hydrocortisone were given ghrelin (5 pmol/kg per min) and saline infusions for 300 min in a randomized, double-blind, placebo-controlled, crossover design. Circulating RBP4 levels were measured at baseline and during a hyperinsulinemic–euglycemic clamp on both study days. To study the direct effects of GH, nine healthy men were treated with GH (2 mg at 2200 h) and placebo for 8 days in a randomized, double-blind, placebo-controlled, crossover study. Serum RBP4 levels were measured before and after treatment, and insulin sensitivity was measured by the hyperinsulinemic–euglycemic clamp technique.ResultsGhrelin acutely decreased peripheral insulin sensitivity. Serum RBP4 concentrations decreased in response to insulin infusion during the saline experiment (mg/l): 43.2±4.3 (baseline) vs 40.4±4.2 (clamp), P<0.001, but this effect was abrogated during ghrelin infusion (mg/l): 42.4±4.5 (baseline) vs 42.9±4.7 (clamp), P=0.73. In healthy subjects, serum RBP4 levels were not affected by GH administration (mg/l): 41.7±4.1 (GH) vs 43.8±4.6 (saline), P=0.09, although GH induced insulin resistance.Conclusionsi) Serum RBP4 concentrations decrease in response to hyperinsulinemia, ii) ghrelin abrogates the inhibitory effect of insulin on circulating RBP4 concentrations, and iii) ghrelin as well as GH acutely induces insulin resistance in skeletal muscle without significant changes in circulating RBP4 levels.

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The STRA6 Receptor Is Essential for Retinol-binding Protein-induced Insulin Resistance but Not for Maintaining Vitamin A Homeostasis in Tissues Other Than the Eye

Journal of Biological Chemistry ◽

10.1074/jbc.m113.484014 ◽

2013 ◽

Vol 288 (34) ◽

pp. 24528-24539 ◽

Cited By ~ 79

Author(s):

Daniel C. Berry ◽

Hugues Jacobs ◽

Gurdeep Marwarha ◽

Aurore Gely-Pernot ◽

Sheila M. O'Byrne ◽

...

Keyword(s):

Insulin Resistance ◽

Vitamin A ◽

Binding Protein ◽

Retinol Binding Protein

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Serum retinol-binding protein 4 levels in polycystic ovary syndrome

Endocrine Connections ◽

10.1530/ec-19-0116 ◽

2019 ◽

Vol 8 (6) ◽

pp. 709-717

Author(s):

Shilpa Lingaiah ◽

Laure Morin-Papunen ◽

Terhi Piltonen ◽

Inger Sundström-Poromaa ◽

Elisabet Stener-Victorin ◽

...

Keyword(s):

Insulin Resistance ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Binding Protein ◽

Serum Levels ◽

Retinol Binding Protein ◽

Enzyme Linked Immunosorbent Assay ◽

Serum Retinol ◽

Ovary Syndrome ◽

Retinol Binding Protein 4

Objective Serum levels of retinol-binding protein 4 (RBP4), an adipokine thought to affect systemic insulin sensitivity, were compared between women with polycystic ovary syndrome (PCOS) and non-PCOS controls to evaluate the association of RBP4 with clinical, hormonal and metabolic parameters of PCOS. Subjects and methods Serum RBP4 levels were analysed in 278 women with PCOS (age range 18–57 years) and 191 non-PCOS controls (age 20–53 years) by enzyme-linked immunosorbent assay. Results Serum levels of RBP4 were increased in women with PCOS compared with control women in the whole population (45.1 ± 24.0 (s.d.) vs 33.5 ± 18.3 mg/L, P < 0.001). Age-stratified analysis showed that serum RBP4 levels were increased in women with PCOS aged ≤30 years compared with controls (47.7 ± 23.5 vs 27.1 ± 10.4 mg/L, P < 0.001), whereas no significant differences were seen in the other age groups. No significant correlations of RBP4 were seen with either steroids or indices of insulin resistance. Conclusions Although serum RBP4 levels were increased in younger women with PCOS compared with age-matched non-PCOS controls, RBP4 does not seem to be a good marker of insulin resistance or other metabolic derangements in women with PCOS.

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Association of serum levels of retinol-binding protein 4 with male sex but not with insulin resistance in obese patients

Archives of Physiology and Biochemistry ◽

10.3109/13813451003631421 ◽

2010 ◽

Vol 116 (2) ◽

pp. 57-62 ◽

Cited By ~ 25

Author(s):

Fatma Ülgen ◽

Christian Herder ◽

Markus C. Kühn ◽

Holger S. Willenberg ◽

Matthias Schott ◽

...

Keyword(s):

Insulin Resistance ◽

Binding Protein ◽

Serum Levels ◽

Retinol Binding Protein ◽

Obese Patients ◽

Retinol Binding Protein 4 ◽

Male Sex

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Effect of intramuscular vitamin A injection on plasma levels of vitamin A and retinol-binding protein in malnourished children

British Journal Of Nutrition ◽

10.1079/bjn19810098 ◽

1981 ◽

Vol 45 (2) ◽

pp. 229-232 ◽

Cited By ~ 4

Author(s):

Vinodini Reddy ◽

M. Mohanram

Keyword(s):

Vitamin A ◽

Binding Protein ◽

Serum Levels ◽

Retinol Binding Protein ◽

Total Vitamin ◽

Normal Children ◽

Retinyl Ester ◽

Malnourished Children ◽

Short Period ◽

Significant Difference

1. Serum levels of retinol-binding protein (RBP), total vitamin A and retinyl ester were measured in twenty-four malnourished children with corneal lesions and nine normal children.2. Initially, the RBP and vitamin A levels were significantly lower in malnourished children than in normal children.3. After intramuscular injection of 30000 μg of aqueous vitamin A, serum levels of total vitamin A were increased significantly at 24 h and tended to fall within 5 d of treatment in both groups.4. Before treatment, retinyl ester accounted for less than 10% of the vitamin in circulation. After vitamin A injection, it increased to 30%, a level much lower than that reported in patients with hypervitaminosis A.5. There was no significant difference between the two groups of children and none of them showed clinical signs of toxicity. These observations indicate that administration of massive doses of vitamin A over a short period will not produce toxic effects even in malnourished children.

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Retinol (vitamin A) and retinol-binding protein serum levels in children with cancer at onset

Nutrition ◽

10.1016/s0899-9007(97)90873-x ◽

1997 ◽

Vol 13 (1) ◽

pp. 17-20 ◽

Cited By ~ 7

Author(s):

Paolo Fiore ◽

Elio Castagnola ◽

Nora Marchese ◽

Carlo Dufour ◽

Alberto Garaventa ◽

...

Keyword(s):

Vitamin A ◽

Binding Protein ◽

Serum Levels ◽

Retinol Binding Protein ◽

Children With Cancer ◽

Protein Serum

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Effects of two different eight-week walking programs on insulin resistance and ER stressrelated markers in pre-menopausal women / Premenopozal kadınlarda 8 haftalık farklı şiddetteki yürüyüş antrenmanlarının insülin direnci ve ER stresiyle ilişkili markerler üzerine etkileri

Turkish Journal of Biochemistry ◽

10.1515/tjb-2016-0047 ◽

2016 ◽

Vol 41 (5) ◽

Author(s):

Yeliz Doğru ◽

Gürbüz Büyükyazı ◽

Cevval Ulman ◽

Fatma Taneli ◽

Hakan Tıkız ◽

...

Keyword(s):

Insulin Resistance ◽

Er Stress ◽

Metabolic Diseases ◽

Retinol Binding Protein ◽

Brisk Walking ◽

Positive Effects ◽

Tnf Α ◽

Menopausal Women ◽

Walking Programs ◽

Walking Group

AbstractObjective: The relationship between exercise and endoplasmic reticulum (ER) stress, insulin resistance, and obesity is a new field of research. To our knowledge, there are no studies examining the effects of walking exercises on ER stress related markers and insulin resistance in pre-menopausal women. To examine the effect of two different eight-week walking programs on the tumor necrosis factor-alpha (TNF-α), Fetuin-A (α2 - Heremans Schmid glycoprotein), c-Jun N-terminal kinase-1 (JNK-1) and retinol- binding protein-4 (RBP-4), the related markers of ER stress and insulin resistance in pre-menopausal women.Methods: Exercise groups (moderate tempo walking group; MTWG; n=11; brisk walking group BWG; n=12) walked five days a week, starting from 30 minutes, gradually increasing up to 51 minutes. BWG walked at ~70-75% and MTWG at ~50-55 of HRRmax. Body mass index (BMI), body fat percentage (%), VOResults: VOConclusion: Both type of walking resulted in similar positive effects on RBP-4. The reduction observed in TNF-α, RBP-4, and the increases in the negative levels of JNK-1 in BWG show the positive effects of brisk walking on ER stress. The reduction in insulin resistance in relation to the possible reductions in ER stress and apoptosis in BWG may be more effective to prevent metabolic diseases.

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