Prediabetes uncovers differential gene expression at fasting and in response to oral glucose load in immune cells

Mallu, Abhiram Charan Tej; Vasudevan, Madavan; Allanki, Srinivas; Nathan, Abel Arul; Ravi, Mahalakshmi M.; Ramanathan, Gowri; Pradeepa, Rajendra; Mohan, Viswanathan; Dixit, Madhulika

doi:10.1016/j.clnu.2020.08.007

Cited by 7 publications

(7 citation statements)

References 69 publications

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“…It would also be worthwhile to determine how different types of commercial insulin preparations; be it rapid‐, intermediate‐ or long‐acting insulin impact the adhesive and homing properties of circulating lymphocytes in diabetic patients. In a recent pilot study from our group, it was observed that PBMCs of pre‐diabetic men exhibit differential gene expression in response to oral glucose load, as opposed to that observed for age‐matched healthy NGT subjects [67]. Thereby, suggesting that in the backdrop of impaired glucose metabolism and insulin resistance, the phenotypic responses of circulating lymphocytes are altered similar to that seen for endothelium during hyperinsulinemia.…”

Section: Discussionmentioning

confidence: 92%

Feeding enhances fibronectin adherence of quiescent lymphocytes through non‐canonical insulin signalling

et al. 2023

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Nutritional availability during fasting and refeeding affects the temporal redistribution of lymphoid and myeloid immune cells among the circulating and tissue‐resident pools. Conversely, nutritional imbalance and impaired glucose metabolism are associated with chronic inflammation, aberrant immunity and anomalous leukocyte trafficking. Despite being exposed to periodic alterations in blood insulin levels upon fasting and feeding, studies exploring the physiological effects of these hormonal changes on quiescent immune cell function and trafficking are scanty. Here, we report that oral glucose load in mice and healthy men enhances the adherence of circulating peripheral blood mononuclear cells (PBMCs) and lymphocytes to fibronectin. Adherence to fibronectin is also observed upon regular intake of breakfast following overnight fasting in healthy subjects. This glucose load‐induced phenomenon is abrogated in streptozotocin‐injected mice that lack insulin. Intra‐vital microscopy in mice demonstrated that oral glucose feeding enhances the homing of PBMCs to injured blood vessels in vivo. Furthermore, employing flow cytometry, Western blotting and adhesion assays for PBMCs and Jurkat‐T cells, we elucidate that insulin enhances fibronectin adherence of quiescent lymphocytes through non‐canonical signalling involving insulin‐like growth factor‐1 receptor (IGF‐1R) autophosphorylation, phospholipase C gamma‐1 (PLCγ‐1) Tyr783 phosphorylation and inside‐out activation of β‐integrins respectively. Our findings uncover the physiological relevance of post‐prandial insulin spikes in regulating the adherence and trafficking of circulating quiescent T‐cells through fibronectin–integrin interaction.

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Section: Discussionmentioning

confidence: 92%

Feeding enhances fibronectin adherence of quiescent lymphocytes through non‐canonical insulin signalling

et al. 2023

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“…Based on these observations and our intra-vital microscopy data, it is fair to speculate that the responsiveness of circulating quiescent T-cells to post-prandial insulin spikes would contribute to their periodic homing and recruitment due to enhanced fibronectin adherence, to lymphoid as well as non-lymphoid organs for routine surveillance, repair and localized immunity. Oral glucose load in healthy individuals also regulates the effector gene expression in innate and adaptive immune cells [8, 26]. Studies have demonstrated that β1 integrins are necessary for the paracrine activity of T-cells including Jurkat T-cells, for expression and release of IFN-γ and VEGF [66].…”

Section: Resultsmentioning

confidence: 99%

“…Additionally, development of immunity in the new born through mother's breast milk, epigenetic modifications during T-cell differentiation, or gross reprogramming of gene expression in immune cells during insulin resistance, all support this inter-dependence [3][4][5][6][7][8][9].…”

Section: Introductionmentioning

confidence: 95%

“…In healthy individuals, acute dietary challenges in the form of oral glucose load following over-night fasting, triggers a well-controlled inflammatory response. These studies are however restricted to observing changes either in serum biochemistry or in gene expression of peripheral blood mononuclear cells (PBMCs) [8,[24][25][26]. Intriguingly, studies addressing the effects of oral glucose load on leukocyte function and trafficking remain elusive.…”

Section: Introductionmentioning

confidence: 99%

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Oral glucose feeding enhances adherence of quiescent lymphocytes to fibronectin via non-canonical insulin signalling

Mallu

Sivagurunathan

Paul

et al. 2021

Preprint

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Impaired glucose metabolism is associated with chronic inflammation, aberrant immunity and anomalous leukocyte trafficking. Conversely, infusion of functional immune cells restores glucose metabolism. Despite being exposed to periodic alterations in blood insulin levels upon fasting and feeding, studies exploring the physiological effects of these hormonal changes on quiescent circulating lymphocytes are missing. Here we find that oral glucose load in healthy men and mice enhance adherence of circulating peripheral blood mononuclear cells (PBMCs) to fibronectin. This led to increased homing of post-load PBMCs to injured blood vessels. Cell culture based experiments on Jurkat-T cells and PBMCs demonstrated that insulin elicits these adhesive effects through a non-canonical signalling involving insulin growth factor-1 receptor (IGF-1R) and phospholipase C gamma-1 (PLCγ-1) mediated activation of integrin β1. Our findings point to the relevance of post-prandial insulin spikes in regulating homing of circulating T-cells to various organs for tissue repair and immunity.

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“…CD4 + and CD8 + T cells interact and balance each other to allow for the body to produce a normal immune response. Diabetes patients are prone to multiple organ complications such as heart, brain, kidney injury, and various infections under the condition of continuous high glucose (HG), which are closely related to the weakened immune function of diabetic patients (Giugliano et al., 2021; Mallu et al., 2021; Marciano et al., 2019). In T2DM patients, due to the uncontrolled regulation of the immune network in the body, a status of glucose metabolism disorder was occurred.…”

Section: Introductionmentioning

confidence: 99%

Myricetin ameliorated prediabetes via immunomodulation and gut microbiota interaction

Gao

Gong

et al. 2022

Food Frontiers

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The global prevalence of prediabetes is on the rise, and it is of value to manage prediabetes and predisposal to diabetes at an early stage. Myricetin is a natural polyhydroxyflavonoid, found in planta with several health benefits. This study aimed to evaluate the effects of myricetin on prediabetes. In vitro assay indicated that the cell viability, endocytosis and phagocytosis of macrophages were inhibited in RAW 264.7 cells under high glucose (HG) levels, concurrent with an increase in reactive oxygen species level. Administration of myricetin at a dose of 10 μM, restored the immunosuppressive effects mediated by HG. Moreover, the viability of Jurkat cells was also inhibited concurrent with inhibition of interleukin-2 (IL-2) and interferon-gamma (IFNγ) expression levels versus increase PD-1 after treated with myricetin at the dose of 10 μM. In a prediabetic mouse model fed with high fat diet, increase in body weight, fat mass, fasting blood glucose, Triglyceride (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were observed. Flow cytometry analysis revealed a significant decrease in CD8 + T cells in the spleen and blood, whereas the expression of PD-1 on CD3 + , CD4 + , and CD8 + T cells in the spleen and lymph was significantly elevated. Administration of myricetin showed a potential hypoglycemic and lipid-lowering effect in both prevention and treatment, in addition to restoration of innate and adaptive immune immunity in mice and confirmed by the in vitro immunomodulation effect. In addition, 16S rRNA showed that myricetin ameliorated prediabetes may be This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

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Prediabetes uncovers differential gene expression at fasting and in response to oral glucose load in immune cells

Cited by 7 publications

References 69 publications

Feeding enhances fibronectin adherence of quiescent lymphocytes through non‐canonical insulin signalling

Feeding enhances fibronectin adherence of quiescent lymphocytes through non‐canonical insulin signalling

Oral glucose feeding enhances adherence of quiescent lymphocytes to fibronectin via non-canonical insulin signalling

Myricetin ameliorated prediabetes via immunomodulation and gut microbiota interaction

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