Vitamin A homeostasis and diabetes mellitus

doi:10.1016/S0899-9007(97)00192-5

Nutrition

Volume 13, Issue 9, September 1997, Pages 804-806

https://doi.org/10.1016/S0899-9007(97)00192-5 Get rights and content

Abstract

Recent studies have shown that plasma concentrations of vitamin A (retinol) and its carrier proteins, retinol-binding protein (RBP), and transthyretin (TTR), are decreased in human subjects with insulin-dependent (IDDM) but not with noninsulin dependent diabetes mellitus (NIDDM). Rats made diabetic with streptozotocin (STZ) have also been shown to have reduced levels of plasma vitamin A while its hepatic concentrations elevate. The circulatory vitamin A levels remained low while its hepatic concentrations were further elevated following supplementation of the vitamin. The reduced circulatory status of vitamin A in diabetic animals was not caused by its impaired intestinal absorption. Further experimental studies have pointed to the fact that IDDM is associated with a deficiency of vitamin A, which is secondary to an impaired transport mechanism of this vitamin from its hepatic storage to the target site, such as retina of the eyes. The diabetes-associated changes in vitamin A metabolism were reversed to normal by insulin treatment. The underlying cause for decreased metabolic availability in uncontrolled diabetes, is not clearly understood. It appears that the increased hepatic store of vitamin A is attributed to a decreased availability of its carrier proteins. Subnormal vitamin A status in poorly controlled diabetic subjects may not respond to vitamin A supplementation, rather it may increase its load in the liver leading to hepatoxicity. These results clearly suggest that there is a need for further research identifying the importance of vitamin A in diabetes mellitus.

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Cited by (68)

All-trans retinoic acid ameliorates glycemic control in diabetic mice via modulating pancreatic islet production of vascular endothelial growth factor-A
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Citation Excerpt :
Vitamin A is an essential component for maintaining immune tolerance and T-cell-mediated immunity [7,8]. Therefore, impaired vitamin A metabolism can affect the autoimmune response and development of T1DM [9]. Several clinical studies showed that the individuals with T1D had decreased circulating levels of vitamin A or RBP4 as compared to the non-diabetics [10–12].
Patients with type 1 diabetes mellitus are associated with impairment in vitamin A metabolism. This study evaluated whether treatment with retinoic acid, the biologically active metabolite of vitamin A, can ameliorate diabetes. All-trans retinoic acid (atRA) was used to treat streptozotocin (STZ)-induced diabetic mice which revealed atRA administration ameliorated blood glucose levels of diabetic mice. This hyperglycemic amelioration was accompanied by an increase in the amount of β cells co-expressed Pdx1 and insulin and by restoration of the vascular laminin expression. The atRA-induced production of vascular endothelial growth factor-A from the pancreatic islets was possibly the key factor that mediated the restoration of islet vascularity and recovery of β−cell mass. Furthermore, the combination of islet transplantation and atRA administration significantly rescued hyperglycemia in diabetic mice. These findings suggest that vitamin A derivatives can potentially be used as a supplementary treatment to improve diabetes management and glycemic control.
Role of vitamin A in type 2 diabetes mellitus biology: Effects of intervention therapy in a deficient state
2015, Nutrition
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The complexity of vitamin A intake is highlighted by the fact that although vitamin A supplementation altered the risk for and outcomes of acute respiratory tract infections in third-world countries; an adverse effect was observed when administered to children in developed countries [56]. In certain cases, it has been observed that vitamin A metabolism affected during the onset of diabetes is not reversed by vitamin A supplementation alone [57]. In streptozotocin-induced diabetes in rats, it was found that vitamin A supplementation could not elevate the serum vitamin A levels, rather hepatic levels of retinol were found to be increased ultimately resulting in hepato-toxicity.
Diabetes has emerged as the biggest pandemic of our times, growing parallel to obesity. Insulin treatment regimens have been unable to completely inhibit protein glycation, which is responsible for the development of increased oxidative stress in diabetic tissues. Coupled with recent evidences that highlight the role of reactive oxygen species in the onset and progression of type 2 diabetes mellitus (T2DM), the antioxidants have taken prime focus as a possible intervention strategy. Studies have established a role of antioxidant vitamins C and E in improving patient condition in the past. Vitamin A, in addition to its role as an antioxidant, boasts a pleiotropic role in cell regulation through its action on gene regulation, maintenance of epithelial cell integrity, and resistance to infection. Studies have also ascribed a role to vitamin A in up-regulating the antioxidant enzyme functions in the body. Additionally, a link has been found between diabetes and deficient vitamin A levels indicating vitamin A supplementation may have a role in T2DM biology. This review therefore focuses on the vitamin A intervention in T2DM patients having deficient in vitamin A.
Protection from diabetic cardiomyopathy — Putative role of the retinoid receptor-mediated signaling
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The Membrane Receptor for Plasma Retinol-Binding Protein, A New Type of Cell-Surface Receptor
2011, International Review of Cell and Molecular Biology
Citation Excerpt :
In addition to vision, known biological functions of vitamin A include its roles in embryonic growth and development, immune competence, reproduction, maintenance of epithelial surfaces, and proper functioning of the adult brain (Drager, 2006; Duester, 2008; Mangelsdorf et al., 1993; Napoli, 1999; Ross and Gardner, 1994). Since vitamin A derivatives have profound effects on cellular growth and differentiation, vitamin A also plays positive or negative roles in a wide range of pathological conditions, such as visual disorders (Travis et al., 2006), cancer (Love and Gudas, 1994; Niles, 2004; Verma, 2003), infectious diseases (Stephensen, 2001), diabetes (Basu and Basualdo, 1997; Yang et al., 2005), teratogenicity (Nau et al., 1994), and skin diseases (Chivot, 2005; Orfanos et al., 1997; Zouboulis, 2001). Except for vision, which depends on the aldehyde form of vitamin A, most of these physiological or pathological functions can be ascribed to retinoic acid's effects on nuclear hormone receptors (Chambon, 1996; Evans, 1994).
Vitamin A is essential for diverse aspects of life ranging from embryogenesis to the proper functioning of most adult organs. Its derivatives (retinoids) have potent biological activities such as regulating cell growth and differentiation. Plasma retinol-binding protein (RBP) is the specific vitamin A carrier protein in the blood that binds to vitamin A with high affinity and delivers it to target organs. A large amount of evidence has accumulated over the past decades supporting the existence of a cell-surface receptor for RBP that mediates cellular vitamin A uptake. Using an unbiased strategy, this specific cell-surface RBP receptor has been identified as STRA6, a multitransmembrane domain protein with previously unknown function. STRA6 is not homologous to any protein of known function and represents a new type of cell-surface receptor. Consistent with the diverse functions of vitamin A, STRA6 is widely expressed in embryonic development and in adult organ systems. Mutations in human STRA6 are associated with severe pathological phenotypes in many organs such as the eye, brain, heart, and lung. STRA6 binds to RBP with high affinity and mediates vitamin A uptake into cells. This review summarizes the history of the RBP receptor research, its expression in the context of known functions of vitamin A in distinct human organs, structure/function analysis of this new type of membrane receptor, pertinent questions regarding its very existence, and its potential implication in treating human diseases.
Alterations in Vitamin A/retinoic acid homeostasis in diet-induced obesity and insulin resistance
2017, Proceedings of the Nutrition Society
Age-dependent changes in fat- and water-soluble vitamins—National Health and Nutrition Examination Surveys study
2022, Frontiers in Medicine

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Review articleVitamin A homeostasis and diabetes mellitus☆

Abstract

Am J Med Sci

Am J Clin Nutr

Metabolism

Diabetes Res Clin Pract

Am J Med

The incidence of vision loss in a diabetic population

Opthalmology

Vitamin A deficiency, xerophthalmia and blindness

Nutr Rev

Vitamin A, B and C in diabetic children

Arch Intern Med

Urinary zinc and its relationships with microalbuminuria in type I diabetics

Biol Trace Elem Res

Effect of diabetes type and treatment on zinc status in diabetes mellitus