The regulatory role of insulin in energy metabolism and leukocyte functions

Cruz-Pineda, Walter David; Parra‐Rojas, Isela; Rodríguez-Ruiz, Hugo Alberto; Illades‐Aguiar, Berenice; Matia‐García, Inés; Garibay‐Cerdenares, Olga Lilia

doi:10.1002/jlb.2ru1220-847r

Cited by 16 publications

(8 citation statements)

References 160 publications

(230 reference statements)

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“…In leukocytes, insulin influences glucose uptake and metabolism, as well as the regulation of some of their immune functions. 35 Our data are consistent with previous findings that showed increased Th1 cells at the systemic level in obese children 32 and in morbidly obese adults, Th1 cells correlated with the degree of insulin resistance. 36 In a community-based Multi-Ethnic Study of Atherosclerosis (MESA), a high proportion of memory CD4+ cells and low proportion of naive CD4+ cells in circulating blood were associated with the prevalence of T2DM.…”

Section: Discussionsupporting

confidence: 93%

“…The activation and metabolic turnover of T cells is accompanied by the positive regulation of the insulin receptor, which allows a greater proliferation capacity, cytokine production and survival, and as a result, a correct activation of these cells. 35,39 Furthermore, T lymphocytes from obese individuals with insulin resistance stimulated in vitro with supraphysiological insulin concentrations showed no increase in AKT phosphorylation or decrease in the Th1/Th2 ratio, nor was there any effect on Th cell differentiation as in lymphocytes from lean controls, since insulin under normal conditions can promote the differentiation of Th cells towards an anti- inflammatory Th2 phenotype. This indicates that lymphocytes from obese individuals have an altered response to insulin.…”

Section: Discussionmentioning

confidence: 92%

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Th1/Th2 Balance in Young Subjects: Relationship with Cytokine Levels and Metabolic Profile

Matia‐García¹,

Vadillo²,

Pelayo³

et al. 2021

JIR

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Purpose:We aim to identify Th1 and Th2 cell clusters in young subjects, including their clinical and metabolic characteristics and the Th1/Th2 balance. Patients and Methods: A total of 100 participants were included. The frequencies of Th1 and Th2 cells in peripheral blood were determined by flow cytometry. Serum C-reactive protein was measured using a turbidimetric assay, and insulin levels were quantified with an enzyme-linked immunosorbent assay. Circulating cytokine levels were analyzed using a multiplex system. Results: A cluster analysis was performed to determine the Th1/Th2 balance in a group of young people, and 3 clusters were formed with the following characteristics: 1) subjects with a higher prevalence of hyperglycemia (38%), dyslipidemia (38-75%), and insulin resistance (50%), as well as a higher percentage of Th1 cells and Th1/Th2 ratio, including elevated IFN-ɣ levels; 2) subjects with a lower prevalence of hyperglycemia (23%) and insulin resistance (15.4%), but a higher prevalence of dyslipidemia (8-85%) with a predominance of Th2 cells, and lower Th1/Th2 ratio; 3) subjects with a lower prevalence of hyperglycemia (6%), insulin resistance (41%), and dyslipidemia (10-63%), as well as a balance of Th1 and Th2 cells and lower Th1/Th2 ratio, including low IFN-ɣ levels. Positive correlations between Th1 cells with IFN-γ, IL-12, and IL-1β and between Th2 cells with IFN-γ, IL-2, and IL-4 were found (p < 0.05). A significant increase in Th1 cells was observed in the presence of hyperglycemia and high LDL-C levels, as well as increased Th2 cells in the absence of abdominal obesity and high blood pressure, including low HDL-C levels. The Th1/Th2 ratio was higher in the group with high cardiometabolic risk (p = 0.03). Conclusion: Th1/Th2 balance is related to metabolic abnormalities that may occur in young population, and thus the timely identification of different phenotypes may help predict an increased cardiometabolic risk.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 92%

Th1/Th2 Balance in Young Subjects: Relationship with Cytokine Levels and Metabolic Profile

Matia‐García¹,

Vadillo²,

Pelayo³

et al. 2021

JIR

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“…The role of insulin signaling in different subsets of leukocytes which may or may not express the insulin receptors (IR), is now beginning to emerge. It was demonstrated that indeed insulin elicits intracellular signaling in human leukocytes, however it is unclear as to what is the functional relevance of this signaling, despite it being disrupted in diabetic patients [42, 43]. Others have shown that insulin primes activated neutrophils toward phagocytosis [1].…”

Section: Resultsmentioning

confidence: 99%

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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“…Insulin is a 5.8 kDa protein which plays an important role in regulating metabolism and enhancement of cell growth [78,79]. The oral use of insulin is still challenging owing to easy degradation in the gastro-intestinal tract.…”

Section: Insulin Deliverymentioning

confidence: 99%

Nanofiber-based systems intended for diabetes

et al. 2021

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Diabetic mellitus (DM) is the most communal metabolic disease resulting from a defect in insulin secretion, causing hyperglycemia by promoting the progressive destruction of pancreatic β cells. This autoimmune disease causes many severe disorders leading to organ failure, lower extremity amputations, and ultimately death. Modern delivery systems e.g., nanofiber (NF)-based systems fabricated by natural and synthetic or both materials to deliver therapeutics agents and cells, could be the harbinger of a new era to obviate DM complications. Such delivery systems can effectively deliver macromolecules (insulin) and small molecules. Besides, NF scaffolds can provide an ideal microenvironment to cell therapy for pancreatic β cell transplantation and pancreatic tissue engineering. Numerous studies indicated the potential usage of therapeutics/cells-incorporated NF mats to proliferate/regenerate/remodeling the structural and functional properties of diabetic skin ulcers. Thus, we intended to discuss the aforementioned features of the NF system for DM complications in detail. Graphic abstract

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The regulatory role of insulin in energy metabolism and leukocyte functions

Cited by 16 publications

References 160 publications

Th1/Th2 Balance in Young Subjects: Relationship with Cytokine Levels and Metabolic Profile

Th1/Th2 Balance in Young Subjects: Relationship with Cytokine Levels and Metabolic Profile

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

Nanofiber-based systems intended for diabetes

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