scholarly journals Natural killer cell-derived exosomal miR-1249-3p attenuates insulin resistance and inflammation in mouse models of type 2 diabetes

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Ying Wang ◽  
Mengwei Li ◽  
Lin Chen ◽  
Huan Bian ◽  
Xiangying Chen ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Natural Killer Cell ◽  
Nk Cells ◽  
Natural Killer ◽  
Ternary Complex ◽  
Killer Cell ◽  
Enhance Insulin Sensitivity

AbstractNatural killer (NK) cells have been suggested to be associated with type 2 diabetes by regulating systemic inflammation. However, the mechanism by which NK cells regulate insulin sensitivity remains unknown. This study shows that NK-derived exosomes from lean mice attenuate obesity-induced insulin resistance and inflammation in mice of type 2 diabetes. Moreover, lean NK-derived exosomes enhance insulin sensitivity and relieve inflammation in adipocytes and hepatocytes. MiR-1249-3p, which is significantly upregulated in lean NK-derived exosomes, can be transferred from NK cells to adipocytes and hepatocytes via exosomes. NK-derived exosomal miR-1249-3p dramatically induces cellular insulin sensitivity and relieves inflammation. Mechanistically, exosomal miR-1249-3p directly targets SKOR1 to regulate the formation of ternary complex SMAD6/MYD88/SMURF1, which mediates glucose homeostasis by suppressing the TLR4/NF-κB signaling pathway. This study reveals an emerging role for NK-derived exosomal miR-1249-3p in remission of insulin resistance, and provides a series of potential therapeutic targets in type 2 diabetes.

scholarly journals Relationship between natural killer cell activity and glucose control in patients with type 2 diabetes and prediabetes

2019 ◽  
Vol 10 (5) ◽  
pp. 1223-1228 ◽  
Author(s):  
Jung Hye Kim ◽  
Kahui Park ◽  
Sang Bae Lee ◽  
Shinae Kang ◽  
Jong Suk Park ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Natural Killer Cell ◽  
Natural Killer ◽  
Glucose Control ◽  
Natural Killer Cell Activity ◽  
Killer Cell ◽  
Cell Activity ◽  
Killer Cell Activity

scholarly journals Natural killer cell levels in adults living with type 2 diabetes: a systematic review and meta-analysis of clinical studies

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Vuyolwethu Mxinwa ◽  
Phiwayinkosi V. Dludla ◽  
Tawanda M. Nyambuya ◽  
Kabelo Mokgalaboni ◽  
Sithandiwe E. Mazibuko-Mbeje ◽  
...  
Keyword(s):  
Systematic Review ◽  
Type 2 Diabetes ◽  
Nk Cells ◽  
Natural Killer ◽  
Nk Cell ◽  
Meta Analysis ◽  
Killer Cell ◽  
Adult Patients ◽  
Increased Risk

Abstract Background Chronic immune activation and hyperglycaemia are a hallmark of type 2 diabetes mellitus (T2D) while natural killer (NK) cells are involved in the pathogenesis of T2D. Dysregulated NK cell responses are associated with an increased risk of cardiovascular disease in patients living with T2D. Objective To provide a comprehensive and systematic evidence-based estimate on the levels of NK cells in patients living with T2D. Results This systematic review and meta-analysis included 13 studies reporting on 491 adult patients with T2D and 1064 nondiabetic controls. The pooled effect estimates showed increased levels of NK cells in adult patients with T2D compared to controls (MD: 0.03 [− 3.20, 3.26], I2 = 97%, p < 0.00001). Conclusion Overall, the evidence presented in this systematic review shows that the changes in NK cells in patients living with T2D are still unclear and further studies are needed.

scholarly journals A prospective observational case-controlled pilot study protocol on natural killer cell activity in patients with type 2 diabetes mellitus taking empagliflozin

2020 ◽  
Author(s):  
Sayak Roy ◽  
Anindita Chatterjee
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Nk Cells ◽  
Natural Killer ◽  
Transforming Growth Factor ◽  
Natural Killer Cell Activity ◽  
Killer Cell ◽  
Cell Activity

Abstract Belonging to the innate immune system, natural killer (NK) cells play crucial roles in various kinds of cancers and other pathologies. The function and development of NK cells are regulated and enhanced by various inflammatory cytokines like common-γ chain family cytokines, transforming growth factor-β, interleukin (IL)-3, IL-10, IL-12, and IL-18. It has been found that their activity, as measured by interferon gamma assay release method, is decreased in Type 2 diabetes mellitus (T2DM) as well as prediabetes and is directly related to the degree of glycemic control. The multiple mechanisms shown by sodium-glucose cotransporter inhibitors (SGLT2Is) to address glycemic as well as non-glycemic inflammatory pathways make them an ideal candidate in most of our obese patients with T2DM since most of them are at higher cardiovascular (CV) risk. Obesity, a common comorbidity in T2DM, is also a known contributor of decreased NK cell activity. Since SGLT2Is have an indirect anti-inflammatory property, hence this study is intended to investigate any change in the NKC activity after initiating empagliflozin over 4 weeks in a cohort of well-controlled diabetic population.

scholarly journals Natural Killer Cell Function, an Important Target for Infection and Tumor Protection, Is Impaired in Type 2 Diabetes

PLoS ONE ◽  
2013 ◽  
Vol 8 (4) ◽  
pp. e62418 ◽  
Author(s):  
Jeannig Berrou ◽  
Sophie Fougeray ◽  
Marion Venot ◽  
Victor Chardiny ◽  
Jean-François Gautier ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Natural Killer Cell ◽  
Natural Killer ◽  
Cell Function ◽  
Killer Cell ◽  
Natural Killer Cell Function ◽  
Important Target ◽  
Tumor Protection

scholarly journals Type 2 diabetes mellitus is associated with altered CD8+T and natural killer cell function in pulmonary tuberculosis

Immunology ◽  
2015 ◽  
Vol 144 (4) ◽  
pp. 677-686 ◽  
Author(s):  
Nathella P. Kumar ◽  
Rathinam Sridhar ◽  
Dina Nair ◽  
Vaithilingam V. Banurekha ◽  
Thomas B. Nutman ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Natural Killer Cell ◽  
Pulmonary Tuberculosis ◽  
Natural Killer ◽  
Cell Function ◽  
Killer Cell ◽  
Natural Killer Cell Function

scholarly journals Common Risk Factors in Relatives and Spouses of Patients with Type 2 Diabetes in Developing Prediabetes

Healthcare ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 1010
Author(s):  
Wei-Hao Hsu ◽  
Chin-Wei Tseng ◽  
Yu-Ting Huang ◽  
Ching-Chao Liang ◽  
Mei-Yueh Lee ◽  
...  
Keyword(s):  
Risk Factors ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Cell Function ◽  
Diabetic Patients ◽  
Β Cell ◽  
Tyg Index ◽  
Β Cell Function

Prediabetes should be viewed as an increased risk for diabetes and cardiovascular disease. In this study, we investigated its prevalence among the relatives and spouses of patients with type 2 diabetes or risk factors for prediabetes, insulin resistance, and β-cell function. A total of 175 individuals were included and stratified into three groups: controls, and relatives and spouses of type 2 diabetic patients. We compared clinical characteristics consisting of a homeostatic model assessment for insulin resistance (HOMA-IR) and beta cell function (HOMA-β), a quantitative insulin sensitivity check index (QUICKI), and triglyceride glucose (TyG) index. After a multivariable linear regression analysis, the relative group was independently correlated with high fasting glucose, a high TyG index, and low β-cell function; the relatives and spouses were independently associated with a low QUICKI. The relatives and spouses equally had a higher prevalence of prediabetes. These study also indicated that the relatives had multiple factors predicting the development of diabetes mellitus, and that the spouses may share a number of common environmental factors associated with low insulin sensitivity.

Vascular dysfunction and insulin stimulated blood flow : impact of physical inactivity and type 2 diabetes

2014 ◽  
Author(s):  
◽  
Leryn J. Boyle
Keyword(s):  
Physical Activity ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Blood Flow ◽  
Insulin Sensitivity ◽  
Endothelial Function ◽  
Physical Inactivity ◽  
Vascular Dysfunction ◽  
Insulin Stimulation

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Individuals with type 2 diabetes (T2D) have blunted femoral artery insulin mediated blood flow which is critical for the delivery and uptake of glucose into skeletal muscle. However, it is unclear in humans the precise mechanisms by which insulin resistance impairs insulin stimulated blood flow. Further, chronic physical inactivity is a powerful stimulus for reduced insulin sensitivity and vascular dysfunction; however, the effects of short term, modest reductions in physical activity are limited. Thus, we examined 1) if inactivity for 5 days would impair endothelial function in healthy individuals (study one) 2) if reducing whole body insulin sensitivity, via 5 days of inactivity, would impair the blood flow response to insulin stimulation in parallel with glycemic control (study two) and 3) phosphorylation of endothelial nitric oxide (eNOS) and endothelin-1 (ET-1) production to insulin stimulation would be decreased and increased, respectively, in insulin resistant individuals (study three). We demonstrated significant reductions in endothelial function with only 5 days of reduced daily steps while blood flow to glucose ingestion was unaltered. Further, in obese humans with type 2 diabetes it does not appear that that the reduction in blood flow to 1 hr of insulin stimulation is due to altered peNOS or ET-1. Collectively, these data suggest that reduced daily physical activity and chronic insulin resistance mediate negative impacts on vascular function and insulin stimulated blood flow and signaling.

Increasing endogenous PPARγ ligands improves insulin sensitivity and protects against diet-induced obesity without side effects of thiazolidinediones

2021 ◽  
Author(s):  
Yu-Hua Tseng ◽  
Lee-Ming Chuang ◽  
Yi-Cheng Chang ◽  
Meng-Lun Hsieh ◽  
Lun Tsou ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Side Effects ◽  
Knockout Mice ◽  
Fasting Glucose ◽  
Binding Mode ◽  
Fluid Retention ◽  
Diet Induced Obesity

Abstract Insulin resistance and obesity are pivotal features of type 2 diabetes mellitus. Peroxisome proliferator-activated receptor γ (PPARγ) is a master transcriptional regulator of systemic insulin sensitivity and energy balance. The anti-diabetic drug thiazolidinediones are potent synthetic PPARγ ligands and insulin sensitizers with undesirable side effects including increased adiposity, fluid retention, and osteoporosis, which limit their clinical use. We and others have proved that 15-keto-PGE2 is an endogenous natural PPARγ ligand. 15-keto-PGE2 is catalyzed by prostaglandin reductase 2 (PTGR2) to become inactive metabolites. We found that 15-keto-PGE2 level is increased in Ptgr2 knockout mice. Ptgr2 knockout mice were protected from diet-induced obesity, insulin resistance, and hepatic steatosis without fluid retention nor reduced bone mineral density. Diet-induced obese mice have drastically reduced 15-keto-PGE2 levels compared to lean mice. Administration of 15-keto-PGE2 markedly improved insulin sensitivity and prevented diet-induced obesity in mice. We demonstrated that 15-keto-PGE2 activates PPARγ through covalent binding to its cysteine 285 residue at helix 3, which restrained its binding pocket between helix 3 and β-sheets of the PPARγ ligand binding domain. This binding mode differs from the helix12-dependent binding mode of thiazolidinediones. We further identified a small-molecule PTGR2 inhibitor BPRPT245, which interferes the interaction between the substrate-binding sites of PTGR2 and 15-keto-PGE2. BPRPT245 increased 15-keto-PGE2 concentration, activated PPARγ, and promoted glucose uptake in adipocytes. BPRPT245 also prevented diet-induced obesity, improved insulin sensitivity and glucose tolerance, lowers fasting glucose without fluid retention and osteoporosis. In humans, reduced serum 15-keto-PGE2 levels were observed in patients with type 2 diabetes compared with controls. Furthermore, serum 15-keto-PGE2 levels correlate inversely with insulin resistance and fasting glucose in non-diabetic humans. In conclusion, we identified a new therapeutic approach to improve insulin sensitivity and protect diet-induced obesity through increasing endogenous natural PPARγ ligands without side effects of thiazolidinediones.

scholarly journals Adipocyte PU.1 knockout promotes insulin sensitivity in HFD-fed obese mice

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Denise E. Lackey ◽  
Felipe C. G. Reis ◽  
Roi Isaac ◽  
Rizaldy C. Zapata ◽  
Dalila El Ouarrat ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Target Genes ◽  
Obese Mice ◽  
Tissue Macrophage

Abstract Insulin resistance is a key feature of obesity and type 2 diabetes. PU.1 is a master transcription factor predominantly expressed in macrophages but after HFD feeding PU.1 expression is also significantly increased in adipocytes. We generated adipocyte specific PU.1 knockout mice using adiponectin cre to investigate the role of PU.1 in adipocyte biology, insulin and glucose homeostasis. In HFD-fed obese mice systemic glucose tolerance and insulin sensitivity were improved in PU.1 AKO mice and clamp studies indicated improvements in both adipose and liver insulin sensitivity. At the level of adipose tissue, macrophage infiltration and inflammation was decreased and glucose uptake was increased in PU.1 AKO mice compared with controls. While PU.1 deletion in adipocytes did not affect the gene expression of PPARg itself, we observed increased expression of PPARg target genes in eWAT from HFD fed PU.1 AKO mice compared with controls. Furthermore, we observed decreased phosphorylation at serine 273 in PU.1 AKO mice compared with fl/fl controls, indicating that PPARg is more active when PU.1 expression is reduced in adipocytes. Therefore, in obesity the increased expression of PU.1 in adipocytes modifies the adipocyte PPARg cistrome resulting in impaired glucose tolerance and insulin sensitivity.

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