scholarly journals Potential Roles of Adipocyte Extracellular Vesicle–Derived miRNAs in Obesity-Mediated Insulin Resistance

2020 ◽  
Author(s):  
Yujeong Kim ◽  
Ok-Kyung Kim
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Signaling Pathway ◽  
Insulin Signaling ◽  
Metabolic Disorders ◽  
Extracellular Vesicle ◽  
Extracellular Mirnas

ABSTRACT Recently, extracellular microRNAs (miRNAs) from adipose tissue have been shown to be involved in the development of insulin resistance. Here, we summarize several mechanisms explaining the pathogenesis of obesity-induced insulin resistance and associated changes in the expression of obesity-associated extracellular miRNAs. We discuss how miRNAs, particularly miR-27a, miR-34a, miR-141-3p, miR-155, miR210, and miR-222, in extracellular vesicles secreted from the adipose tissue can affect the insulin signaling pathway in metabolic tissue. Understanding the role of these miRNAs will further support the development of therapeutics for obesity and metabolic disorders such as type 2 diabetes.

scholarly journals 1197Identification of insulin signaling pathway-related circulating circRNAs as novel biomarkers of type 2 diabetes

2021 ◽  
Vol 50 (Supplement_1) ◽  
Author(s):  
Yu-xiang Yan ◽  
Ya-Ke Lu ◽  
Xi Chu ◽  
Yue Sun ◽  
Jing Dong
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Signaling Pathway ◽  
Insulin Signaling ◽  
Akt Signaling ◽  
Insulin Signaling Pathway ◽  
Luciferase Reporter ◽  
Mirna Targets ◽  
Novel Biomarkers

Abstract Background The underlying molecular mechanism of type 2 diabetes (T2D) and insulin resistance is that abnormalities occur in the complex insulin signaling pathway. Circular RNAs (circRNAs) are involved in the development of diseases by regulating gene expression and become promising novel biomarkers for diseases. This study screened and validated the insulin signaling pathway-related circulating circRNAs, which are associated with T2D. Methods Based on circRNA microarray, candidate circRNAs involved in the insulin PI3K/Akt signaling pathway were selected and validated by RT-qPCR. The association between circRNAs and T2D and their clinical significance were further assessed by logistic regression model, correlation analysis and ROC curve in a large cohort. The miRNA targets of validated circRNAs was verified by dual-luciferase reporter assay. Results A total of 370 upregulated circRNAs and 180 downregulated circRNAs were differentially expressed between new T2D cases and controls. hsa_circ_0063425, hsa_circ_0056891 and hsa_circ_0104123 were selected as candidate circRNAs for validation. Low expressed circ_0063425 and hsa_circ_0056891 were independent predictors of T2D, impaired fasting glucose (IFG) and insulin resistance. The two-circRNA panel had a high diagnostic accuracy for discriminating T2D and IFG from healthy controls. miR-19a-3p and miR-1-3p were identified as the miRNA targets of hsa_circ_0063425 and hsa_circ_0056891, respectively. Significantly positive correlations were found between the expression levels of AKT and hsa_circ_0063425, PI3K and hsa_circ_0056891, in the total sample and subgroups stratified by glucose levels. Conclusion hsa_circ_0063425 and hsa_circ_0056891 are valuable circulating biomarkers for early detection of T2D, which may be involved in regulation of PI3K/AKT signaling. Key messages Insulin signaling pathway-related circulating circRNAs was identification as novel biomarkers of type 2 diabetes. Keywords circRNA; type 2 diabetes; insulin signaling; biomarker.

scholarly journals An Update to the WISP-1/CCN4 Role in Obesity, Insulin Resistance and Diabetes

Medicina ◽  
2021 ◽  
Vol 57 (2) ◽  
pp. 100
Author(s):  
Małgorzata Mirr ◽  
Maciej Owecki
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Energy Homeostasis ◽  
Peripheral Tissues ◽  
Insulin Resistant ◽  
Highly Active ◽  
Underlying Processes

Insulin resistance refers to the diminished response of peripheral tissues to insulin and is considered the major risk factor for type 2 diabetes. Although many possible mechanisms have been reported to develop insulin resistance, the exact underlying processes remain unclear. In recent years, the role of adipose tissue as a highly active metabolic and endocrine organ, producing proteins called adipokines and their multidirectional activities has gained interest. The physiological effects of adipokines include energy homeostasis and insulin sensitivity regulation. In addition, an excess of adipose tissue is followed by proinflammatory state which results in dysregulation of secreted cytokines contributing to insulin resistance. Wingless-type (Wnt) inducible signalling pathway protein-1 (WISP-1), also known as CCN4, has recently been described as a novel adipokine, whose circulating levels are elevated in obese and insulin resistant individuals. Growing evidence suggests that WISP-1 may participate in the impaired glucose homeostasis. In this review, we characterize WISP-1 and summarize the latest reports on the role of WISP-1 in obesity, insulin resistance and type 2 diabetes.

scholarly journals Role of Gut Microbiome on Metabolic Disorders

2020 ◽  
pp. 21-35
Author(s):  
Ifeanyi O. Oshim ◽  
Nneka R. Agbakoba ◽  
Evelyn U. Urama ◽  
Oluwayemisi Odeyemi ◽  
Nkechi A. Olise ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Intestinal Permeability ◽  
Visceral Adipose Tissue ◽  
Gut Microbiome ◽  
Metabolic Disorders ◽  
Ppar Γ ◽  
Visceral Adipose

Microbiome that reside in the human gut are key contributors to host metabolism and are considered potential sources of novel therapeutics in metabolic disorders. This review discusses the role of gut microbiome in the pathogenesis of obesity, type 2 diabetes mellitus (T2DM), chronic kidney disease and cardiovascular disease. Gut microbiome remains quite stable, although changes take place between birth and adulthood due to external influences, such as diet, disease and environment. Understanding these changes is important to predict diseases and develop therapies. In gut heamostasis, Gut microbiome converts high fibres intake into short-chain fatty acids like butyrate, propionate and acetate which normalize intestinal permeability and alter de novo lipogenesis and gluconeogenesis through reduction of free fatty acid production by visceral adipose tissue. This effect contributes to reduce food intake and to improve glucose metabolism. Propionate can also bind to G protein coupled receptors (GPR)-43 expressed on lymphocytes in order to maintain appropriate immune defence. Butyrate activates peroxisome proliferator-activated receptor-γ (PPAR-γ) leading to beta-oxidation and oxygen consumption, a phenomenon contributing to maintain anaerobic condition in the gut lumen. In contrast, diets most especially western diet consisting among others of high fat and high salt content has been reported to cause gut dysbiosis. This alteration of gut microbiome result to chronic bacterial translocation and increased intestinal permeability that can drive a systemic inflammation leading to macrophage influx into visceral adipose tissue, activation of hepatic kuffer cells and insulin resistance in type 2 diabetes. This effect contributes to lower mucus thickness, decrease butyrate and propionate producing bacteria, L-cells secrete less gut peptides, lack of PPAR-γ activation lead to higher oxygen available for the microbiome at the proximity of the mucosa and increases the proliferation of Enterobacteriaceae with commensurate increase in opportunistic pathogens. However, Gut microbiome are major biomarker for early prognosis of diabetes and other metabolic disorders.

More than a simple storage organ: Adipose tissue as a source of adipokines involved in cardiovascular disease

2013 ◽  
Vol 110 (10) ◽  
pp. 641-650 ◽  
Author(s):  
Gersina Rega-Kaun ◽  
Christoph Kaun ◽  
Johann Wojta
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Overweight And Obesity ◽  
Therapeutic Approaches ◽  
Storage Organ ◽  
Pathophysiological Role ◽  
Metabolically Healthy

SummaryOverweight and obesity in many countries have developed into a serious health problem by themselves and by their impact on other pathologies such as insulin resistance, type 2 diabetes, hypertension, heart disease and cancer. The modulation of these diseases by adipose tissue-derived biomolecules, so-called adipokines, could be the key to differentiate between metabolically healthy and unhealthy obesity. This review will discuss the pathophysiological role of selected adipokines, primarily focusing on cardiovascular diseases. Furthermore, we will highlight possible therapeutic approaches, which target these biomolecules.

scholarly journals N1-Methylnicotinamide Improves Hepatic Insulin Sensitivity via Activation of SIRT1 and Inhibition of FOXO1 Acetylation

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Jingfan Zhang ◽  
Yu Chen ◽  
Cong Liu ◽  
Ling Li ◽  
Ping Li
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Blood Glucose ◽  
Insulin Sensitivity ◽  
Signaling Pathway ◽  
Insulin Signaling ◽  
Related Proteins

Objective. To explore the effects of N1-methylnicotinamide (MNAM) on insulin resistance and glucose metabolism in obese type 2 diabetes mellitus (T2DM) mice and regulatory mechanisms of the NAD-dependent deacetylase sirtuin-1 (SIRT1)/forkhead box protein O1 (FOXO1) pathway. Methods. Blood glucose and insulin levels were examined in mice. HE and oil red O staining were used to observe the effects of MNAM on liver lipid deposition in ob/ob mice. Real-time PCR and Western blotting were used to detect expression of gluconeogenesis, insulin signaling-related proteins, and SIRT1/FOXO1 pathway-related proteins. L-O2 cells were cultured as a model of insulin resistance, and MNAM and SIRT1 inhibitors were administered in vivo. Residual glucose and insulin signaling-related proteins were detected and the mechanisms associated with the SIRT1/FOXO1 signaling pathway in insulin resistance explored. Results. MNAM can effectively reduce levels of fasting blood glucose and insulin, improve liver morphology, and reduce lipid accumulation in obese type 2 diabetes mellitus mice. MNAM also downregulates the key proteins in the gluconeogenesis pathway in the liver, upregulates Sirt1 expression, and reduces acetylation of the FOXO1 protein. In vitro, MNAM could promote the glucose uptake capacity of L-O2 cells induced by palmitic acid (PA), a saturated fatty acid that induces IR in various scenarios, including hepatocytes, improving insulin resistance. As Sirt1 expression was inhibited, the reduction of hepatocyte gluconeogenesis and the regulation of the insulin signaling pathway by MNAM were reversed. Conclusion. MNAM activates SIRT1 and inhibits acetylation of FOXO1, which in turn regulates insulin sensitivity in type 2 diabetic mice, leading to a reduction of hepatic glucose output and improvement of insulin resistance.

scholarly journals AB0083 STUDY OF THE ROLE OF ANGIOPOIETIN-LIKE PROTEIN TYPE 4 IN METABOLIC DISORDERS CAUSED BY INFLAMMATION IN RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1341.2-1341
Author(s):  
A. Aleksandrov ◽  
V. Aleksandrov ◽  
L. Shilova
Keyword(s):  
Rheumatoid Arthritis ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Blood Serum ◽  
Disease Activity ◽  
Metabolic Disorders ◽  
Healthy Individuals

Background:Objectives:To assess the potential role of angiopoietin-like protein type 4 (ANGPTL4) in metabolic disorders caused by inflammation in rheumatoid arthritis (RA).Methods:The study included 88 patients with significant RA, 64 patients with other rheumatic diseases (RD) (36 patients with osteoarthritis (OA); 28 patients with psoriatic arthritis (PsA); 17 patients with ankylosing spondylitis (AS)) and 32 healthy individuals. Estimation of ANGPTL4 was carried out by enzyme immunoassay using the commercial test system “RayBio Human ANGPTL4 ELISA Kit” (RayBiotech, USA) in blood serum. Levels of ESR, CRP, RF, antibodies to cyclic citrullinated peptide (anti-CCP) and modified vimentin (anti-MCV) in the ELISA test were determined for all patients with RA.Results:The level of ANGPTL4 in the blood serum of patients with RA was significantly higher than in healthy people (p <0.001) and patients with other RD (p = 0.012 compared with OA; p = 0.046 with PsA; p = 0.008 with AS). ANGPTL4 indices in patients with RA correlated with the age of onset of RA (r = -0.658, p <0.001), disease activity according to DAS-28 (r = 0.449, p = 0.001), level of education (r = 0.235, p = 0.029), dose of glucocorticoid hormones (r = 0.321, p = 0.009) and methotrexate (r = -0.496, p = 0.05), the presence of osteopenia (r = 0.44), signs of kidney damage - proteinuria (r = 0.309, p = 0.037) and hypoalbuminemia (r = 0.386, p = 0.022), as well as with CRP levels (r = 0.488, p = 0.003), ESR (r = 0.458, p = 0.002), serum vitamin D (r = -0.417) and urinary calcium when recalculated to creatinine (r = 0.797, p = 0.032).Patients with RA showed a high frequency of insulin resistance (according to the HOMA-IR index) (1.27 [0.84–1.62] in patients with RA; 0.76 [0.44–1.02] in healthy individuals; p <0.001) and the presence of coronary heart disease, as well as a positive correlation between disease activity (according to DAS-28) and insulin resistance (according to the HOMA-IR index) (p = 0.033).Higher values of C-reactive protein (p = 0.04) and serum ANGPTL4 levels (p = 0.042, compared with patients with RA without type 2 diabetes; p = 0.026, compared with healthy individuals) were determined in the group of patients with RA with the presence of type 2 diabetes. ANGPTL4 acts as an inhibitor of lipoprotein lipase. His contribution to the development of dyslipidemia in RA can be demonstrated by the results we obtained when comparing groups of patients with / without signs of metabolic syndrome (MS). A positive correlation between ANGPTL4 and triglyceride levels (r = 0.42, p = 0.018) was found. An increase in the level of ANGPTL4 in blood serum of patients with RA with MS (p = 0.027 compared with RA without MS) can predict the development of cardiac pathology in this group of patients.Conclusion:ANGPTL4 is directly involved in the regulation of glucose homeostasis, lipid metabolism, and insulin sensitivity. Cardiovascular diseases associated with atherosclerosis, insulin resistance and metabolic syndrome are known as the most common extraarticular manifestations of RA; the study of the role of ANGPTL4 in metabolic disorders caused by inflammation can show a new direction in the development of laboratory and therapeutic technologies in RA.Disclosure of Interests:None declared

scholarly journals Sphingolipids as a Culprit of Mitochondrial Dysfunction in Insulin Resistance and Type 2 Diabetes

2021 ◽  
Vol 12 ◽  
Author(s):  
Kamila Roszczyc-Owsiejczuk ◽  
Piotr Zabielski
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Protein Kinase ◽  
Mitochondrial Dysfunction ◽  
Signaling Pathway ◽  
Mitochondrial Function ◽  
Insulin Signaling ◽  
Skeletal Muscles ◽  
Insulin Signaling Pathway

Insulin resistance is defined as a complex pathological condition of abnormal cellular and metabolic response to insulin. Obesity and consumption of high-fat diet lead to ectopic accumulation of bioactive lipids in insulin-sensitive tissues. Intracellular lipid accumulation is regarded as one of the major factors in the induction of insulin resistance and type 2 diabetes (T2D). A significant number of studies have described the involvement of ceramides and other sphingolipids in the inhibition of insulin-signaling pathway in both skeletal muscles and the liver. Adverse effects of sphingolipid accumulation have recently been linked to the activation of protein kinase Cζ (PKCζ) and protein phosphatase 2A (PP2A), which, in turn, negatively affect phosphorylation of serine/threonine kinase Akt [also known as protein kinase B (PKB)], leading to decreased glucose uptake in skeletal muscles as well as increased gluconeogenesis and glycogenolysis in the liver. Sphingolipids, in addition to their direct impact on the insulin signaling pathway, may be responsible for other negative aspects of diabetes, namely mitochondrial dysfunction and deficiency. Mitochondrial health, which is characterized by appropriate mitochondrial quantity, oxidative capacity, controlled oxidative stress, undisturbed respiratory chain function, adenosine triphosphate (ATP) production and mitochondrial proliferation through fission and fusion, is impaired in the skeletal muscles and liver of T2D subjects. Recent findings suggest that impaired mitochondrial function may play a key role in the development of insulin resistance. Mitochondria stay in contact with the endoplasmic reticulum (ER), Golgi membranes and mitochondria-associated membranes (MAM) that are the main places of sphingolipid synthesis. Moreover, mitochondria are capable of synthesizing ceramide though ceramide synthase (CerS) activity. Recently, ceramides have been demonstrated to negatively affect mitochondrial respiratory chain function and fission/fusion activity, which is also a hallmark of T2D. Despite a significant correlation between sphingolipids, mitochondrial dysfunction, insulin resistance and T2D, this subject has not received much attention compared to the direct effect of sphingolipids on the insulin signaling pathway. In this review, we focus on the current state of scientific knowledge regarding the involvement of sphingolipids in the induction of insulin resistance by inhibiting mitochondrial function.

scholarly journals RGC32 deficiency protects against high-fat diet-induced obesity and insulin resistance in mice

2014 ◽  
Vol 224 (2) ◽  
pp. 127-137 ◽  
Author(s):  
Xiao-Bing Cui ◽  
Jun-Na Luan ◽  
Jianping Ye ◽  
Shi-You Chen
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
High Fat Diet ◽  
Tolerance Test ◽  
High Fat ◽  
Diet Induced Obesity

Obesity is an important independent risk factor for type 2 diabetes, cardiovascular diseases and many other chronic diseases. Adipose tissue inflammation is a critical link between obesity and insulin resistance and type 2 diabetes and a contributor to disease susceptibility and progression. The objective of this study was to determine the role of response gene to complement 32 (RGC32) in the development of obesity and insulin resistance. WT and RGC32 knockout (Rgc32−/− (Rgcc)) mice were fed normal chow or high-fat diet (HFD) for 12 weeks. Metabolic, biochemical, and histologic analyses were performed. 3T3-L1 preadipocytes were used to study the role of RGC32 in adipocytes in vitro. Rgc32−/− mice fed with HFD exhibited a lean phenotype with reduced epididymal fat weight compared with WT controls. Blood biochemical analysis and insulin tolerance test showed that RGC32 deficiency improved HFD-induced dyslipidemia and insulin resistance. Although it had no effect on adipocyte differentiation, RGC32 deficiency ameliorated adipose tissue and systemic inflammation. Moreover, Rgc32−/− induced browning of adipose tissues and increased energy expenditure. Our data indicated that RGC32 plays an important role in diet-induced obesity and insulin resistance, and thus it may serve as a potential novel drug target for developing therapeutics to treat obesity and metabolic disorders.

Sign in / Sign up

Export Citation Format

Share Document