Vitamin A and Its Multi-Effects on Pancreas: Recent Advances and Prospects

Zhou, Yunting; Wang, Huiying; Zhou, Junming; Qiu, Shanhu; Cai, Tingting; Li, Huiqin; Zheng, Shen; Hu, Yun; Ding, Bo; Luo, Min; Huang, Rong; Yan, Rengna; Xu, Wei; He, Cong; Li, Fengfei; Sun, Zilin; Ma, Jianhua

doi:10.3389/fendo.2021.620941

Cited by 17 publications

(10 citation statements)

References 101 publications

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Section: Retinoid Actions In Pancreatic Developmentmentioning

confidence: 99%

“…The RA-signaling pathway plays critical roles in a wide range of developmental processes at multiple stages during embryogenesis [34]. In the pancreas, RA signaling is necessary for the onset of pancreagenesis; previous studies have demonstrated that inhibition of this RA signaling pathway leads to pancreas agenesis [35]. High levels of RA are crucial for initial pancreas specification, and RA is used in several protocols for stem cell differentiation and for pancreatic endoderm specification in culture.…”

Section: Retinoid Actions In Pancreatic Developmentmentioning

confidence: 99%

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Pancreatic Ductal Adenocarcinoma: New Insights into the Actions of Vitamin A

Aguila¹,

Tang²,

Gudas³

2022

Oncol Res Treat

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Background: Pancreatic ductal adenocarcinoma (PDAC) is a gland-forming malignancy arising in the pancreas. It is estimated that in developed countries the incidence of PDAC will continue to rise, and PDAC is now the fourth leading cause of cancer-related deaths in the USA. The mortality of PDAC patients closely parallels the incidence rate, as this malignancy generally remains asymptomatic until it reaches an advanced stage. Summary: The poor prognosis results from the aggressive nature of the tumor, late detection, and resistance to chemotherapy and radiotherapy. Retinoids, vitamin A (retinol) and its metabolites, such as retinoic acid (RA), play critical roles in important biological functions, including cell growth and differentiation, development, metabolism, and immunity. The actions of retinoids in maintaining normal pancreatic functions have generated considerable research interest from investigators interested in understanding and treating PDAC. Altered expression of retinoid receptors and other RA signaling pathway genes in human cancers offers opportunities for target discovery, drug design, and personalized medicine for distinct molecular retinoid subtypes. Key messages: The goals of this review are to explore the potential activities of retinoids in the pancreas, to assess the evidence that retinoid functions become dysregulated in PDAC, and to describe the actions of retinoids in new therapies developed to increase patient survival.

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Section: Retinoid Actions In Pancreatic Developmentmentioning

confidence: 99%

Section: Retinoid Actions In Pancreatic Developmentmentioning

confidence: 99%

Pancreatic Ductal Adenocarcinoma: New Insights into the Actions of Vitamin A

Aguila¹,

Tang²,

Gudas³

2022

Oncol Res Treat

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“…The plasma level of VA appears to be low in human patients with type 1 diabetes but elevated in those with T2DM [82,83]. VA is stored in pancreatic stellate cells [84]. RA treatment (0.5 mg/mouse intraperitoneally every other day) for 6 weeks is able to delay the onset of diabetes in NOD/Scid mice [85].…”

Section: The Effects Of Ra On Metabolismmentioning

confidence: 99%

“…Both mouse and rat studies have attributed the benefits of RA treatment to the improvement of pancreatic β cell functions [85,86]. More studies are needed to understand the roles of VA in the control of pancreatic functions, as discussed in [84]. In addition, the RA effects may be attributed to the regulation of glucose metabolism [87].…”

Section: The Effects Of Ra On Metabolismmentioning

confidence: 99%

The Interactions of Insulin and Vitamin A Signaling Systems for the Regulation of Hepatic Glucose and Lipid Metabolism

Chen

2021

Cells

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The pandemics of obesity and type 2 diabetes have become a concern of public health. Nutrition plays a key role in these concerns. Insulin as an anabolic hormonal was discovered exactly 100 years ago due to its activity in controlling blood glucose level. Vitamin A (VA), a lipophilic micronutrient, has been shown to regulate glucose and fat metabolism. VA’s physiological roles are mainly mediated by its metabolite, retinoic acid (RA), which activates retinoic acid receptors (RARs) and retinoid X receptors (RXRs), which are two transcription factors. The VA status and activations of RARs and RXRs by RA and synthetic agonists have shown to affect the glucose and lipid metabolism in animal models. Both insulin and RA signaling systems regulate the expression levels of genes involved in the regulation of hepatic glucose and lipid metabolism. Interactions of insulin and RA signaling systems have been observed. This review is aimed at summarizing the history of diabetes, insulin and VA signaling systems; the effects of VA status and activation of RARs and RXRs on metabolism and RAR and RXR phosphorylation; and possible interactions of insulin and RA in the regulation of hepatic genes for glucose and lipid metabolism. In addition, some future research perspectives for understanding of nutrient and hormone interactions are provided.

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“…Retinoic acid, as a product of retinol catabolism, can maintain the activity of vitamin A by activating retinoic acid receptor (RAR) and retinoid acid X receptor (RXR). Studies have confirmed that retinoid is highly associated with diabetes, islet function, and glucose and lipid metabolism by regulating the transcription of downstream target genes [ 12–14 ]. The RXRs are nuclear receptors that mediate the biological effects of retinoids by their involvement in retinoic acid-mediated genes activation.…”

Section: Introductionmentioning

confidence: 99%

Association between functional genetic variants in retinoid X receptor-α/γand the risk of gestational diabetes mellitus in a southern Chinese population

Song

Zheng

et al. 2021

Bioscience Reports

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To clarify the effect of retinoid X receptor-a/g (RXR-α/γ) genes functional genetic variants (RXR-α rs4842194 G>A, RXR-γ rs100537 A>G and rs2134095 T>C) on the risk of gestational diabetes mellitus (GDM), a case-control study with 573 GDM patients and 740 pregnant women with normal glucose tolerance was performed in Guangxi area of China. An odds ratio (OR) with its corresponding 95%CI was used to assess the strengths of the association between genetic variation and GDM. After adjustment of age and pre-BMI, the logistic regression analysis showed that the rs2134095 was significantly associated with GDM risk (CC vs. TT/TC: adjusted OR=0.71, 95%CI=0.56~0.90) in all subjects, and this result remained highly significant after Bonferroni’s correction for multiple testing (P=0.004). The stratified analysis showed that rs2134095 was significantly associated with the risk of GDM among age>30 years (adjusted OR=0.61, 95%CI=0.39~0.97), BMI>22 kg/m2 (adjusted OR=0.46, 95%CI= 0.30~0.70), SBP>120mmHg (adjusted OR=1.96, 95%CI= 1.14~3.36), HbA1c<6.5%(adjusted OR=1.41, 95%CI=1.11~1.78), TG≤1.7mmol/L(adjusted OR=2.57,95%CI=1.45~4.53), TC≤ 5.18mmol/L (adjusted OR=1.58, 95%CI=1.13~2.22), HDL-c≤1.5mmol/L(adjusted OR=1.70, 95%CI= 1.16~2.49) and LDL-c> 3.12 mmol/L(adjusted OR= 1.47, 95%CI= 1.08~2.00) subjects, under the recessive genetic model. We also found that rs2134095 interacted with age (Pinteraction=0.039), pre-BMI (Pinteraction=0.040) and TG (Pinteraction=0.025) influencing individual's genetic susceptibility to GDM. The rs2134095 T>C is significantly associated with the risk of GDM by effect of a single locus and / or complex joint gene-gene and gene-environment interactions. Larger sample-size and different population studies are required to confirm the findings.

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Vitamin A and Its Multi-Effects on Pancreas: Recent Advances and Prospects

Cited by 17 publications

References 101 publications

Pancreatic Ductal Adenocarcinoma: New Insights into the Actions of Vitamin A

Pancreatic Ductal Adenocarcinoma: New Insights into the Actions of Vitamin A

The Interactions of Insulin and Vitamin A Signaling Systems for the Regulation of Hepatic Glucose and Lipid Metabolism

Association between functional genetic variants in retinoid X receptor-α/γand the risk of gestational diabetes mellitus in a southern Chinese population

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