scholarly journals MicroRNAs in Insulin Resistance and Obesity

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Michael D. Williams ◽  
Geraldine M. Mitchell
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Messenger Rna ◽  
Physiological Role ◽  
Mrna Translation ◽  
Aberrant Expression ◽  
Peripheral Tissues ◽  
Pancreatic Islets Of Langerhans ◽  
Diabetes And Obesity

MicroRNAs (miRNAs) are a class of short, single-stranded non-protein coding gene products which can regulate the gene expression through post-transcriptional inhibition of messenger RNA (mRNA) translation. They are known to be involved in many essential biological processes including development, insulin secretion, and adipocyte differentiation. miRNAs are involved in complex metabolic processes, such as energy and lipid metabolism, which have been studied in the context of diabetes and obesity. Obesity, hyperlipidemia (elevated levels of blood lipids), and insulin resistance are strongly associated with the onset of type 2 diabetes. These conditions are also associated with aberrant expression of multiple essential miRNAs in pancreatic islets of Langerhans and peripheral tissues, including adipose tissue. A thorough understanding of the physiological role these miRNAs play in these tissues, and changes to their expression under pathological conditions, will allow researchers to develop new therapeutics with the potential to correct the aberrant expression of miRNAs in type 2 diabetes and obesity.

Abstract 209: Dimethylarginine Dimethylaminohydrolase 1 and Insulin Resistance

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Sophie E Piper ◽  
James M Leiper
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Plasma Glucose ◽  
Knockout Mice ◽  
Physiological Role ◽  
Causal Link ◽  
Chow Diet ◽  
Dimethylarginine Dimethylaminohydrolase

Type 2 diabetes is a prevalent metabolic condition and is the result of an impaired response to insulin. Insulin resistance and type 2 diabetes are clearly associated with obesity and the secondary cardiovascular complications of this condition are serious and life threatening. Asymemetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthases and increased levels are seen in multiple pathologies. Increased plasma levels of ADMA have been associated with patients with type 2 diabetes, insulin resistance and obesity, although a causal link between ADMA and diabetes has not been established. Dimethylarginine dimethylaminohydrolase (DDAH) is the enzyme that catalyses the metabolism of ADMA. There are two isoforms of the enzyme which are both involved in the control of ADMA and NO. The interplay of insulin with NO release is well established but the initial causes for the onset of insulin resistance are not well defined. Elevated levels of ADMA are linked to insulin resistance and transgenic mice that over-express ddah1 show increased insulin sensitivity. Of note is that metformin, an insulin sensitising drug that is widely used in the treatment of insulin resistance, reduces plasma glucose and ADMA concentrations. In order to elucidate the physiological role of DDAH1 in glucose homeostasis we investigated the glucose handling in a ddah1 global knockout model. Intra-peritoneal glucose tolerance tests in ddah1 global knockout mice demonstrate insulin resistance. Baseline plasma glucose levels were 25% higher in ddah1 knockouts and peak levels were 53% higher in ddah1 knockouts. The kinetics of plasma glucose accumulation and clearance in ddah1 knockout mice suggests dysfunction in both the liver and skeletal muscle. On a normal chow diet, hepatocyte specific ddah1 knockout mice and skeletal muscle specific ddah1 knockout mice show no insulin resistance. On a high fat diet however the hepatocyte specific ddah1 knockout mice show significant insulin resistance and lower metabolic rate than their fat fed wild-type counterparts. These studies demonstrate for the first time a causal link between ADMA accumulation and insulin resistance. Furthermore these data establish DDAH1 activity is a significant regulator of insulin resistance.

scholarly journals Obesity and Insulin Resistance: An Abridged Molecular Correlation

2013 ◽  
Vol 6 ◽  
pp. LPI.S10805 ◽  
Author(s):  
Biswajit Mukherjee ◽  
Chowdhury M. Hossain ◽  
Laboni Mondal ◽  
Paramita Paul ◽  
Miltu K. Ghosh
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Molecular Mechanisms ◽  
Physiological Role ◽  
Cardiovascular Complications ◽  
Vital Role ◽  
Diabetic Patients ◽  
Predisposing Factor ◽  
Main Culprit

A relationship between obesity and type 2 diabetes is now generally well accepted. This relationship represents several major health hazards including morbid obesity and cardiovascular complications worldwide. Diabetes mellitus is a complex metabolic disorder characterized by impaired insulin release and insulin resistance. Lipids play an important physiological role in skeletal muscle, heart, liver and pancreas. Deregulation of fatty acid metabolism is the main culprit for developing insulin resistance and type 2 diabetes. A predominant predisposing factor to developing obesity, insulin resistance and type 2 diabetes is the permanent elevation of free fatty acids in plasma followed by impaired utilization of lipids by muscle. Diabetes-induced inflammation and oxidative stress have also vital role for development of insulin resistance in diabetic patients. The present review is intended to describe the correlation between lipids, obesity and insulin resistance based on current literature, in order to elucidate involved molecular mechanisms in depth.

scholarly journals Aberrant Expression of Long Non-Coding RNAs in Newly Diagnosed Type 2 Diabetes Indicates Potential Roles in Chronic Inflammation and Insulin Resistance

2017 ◽  
Vol 43 (6) ◽  
pp. 2367-2378 ◽  
Author(s):  
Xiaoli Wang ◽  
Xiangyun Chang ◽  
Peipei Zhang ◽  
Ling Fan ◽  
Ting Zhou ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Target Genes ◽  
Chinese Patients ◽  
Control Group ◽  
Newly Diagnosed ◽  
Aberrant Expression ◽  
Healthy Control ◽  
Non Coding Rnas

Background/Aims: Long non-coding RNAs (lncRNAs) have emerged as key players in several biological processes and complex diseases. The risk of type 2 diabetes (T2D) is determined by a combination of environmental factors and genetic susceptibility. The purpose of this study was to identify aberrant lncRNAs involved in T2D pathogenesis. Methods: Microarray analysis was performed using whole blood samples from patients newly diagnosed with T2D and healthy controls. Pathway and Gene Ontology (GO) analyses were utilized to annotate the target genes. Coding non-coding co-expression (CNC) analysis was performed to construct a co-expression network. Results: We found 55 lncRNAs and 202 mRNAs were differentially expressed in the T2D group compared to the healthy control group. Pathway and GO analyses demonstrated that dysregulated mRNAs were mainly associated with immune regulation, inflammation, and insulin resistance, whereas CNC analysis identified 10 pairs of co-expressed lncRNA-mRNAs in our patient cohort (R > 0.99). Furthermore, expression of the top three upregulated lncRNAs in the T2D group was correlated with measures of glycometabolism (P < 0.05). Conclusion: This study identified aberrantly expressed lncRNAs and mRNAs in Han Chinese patients with T2D, and demonstrated that dysregulated lncRNAs may have roles in T2D pathogenesis through regulation of inflammation and insulin resistance.

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 Some mechanisms of inflammation development in type 2 diabetes mellitus

2021 ◽  
Vol 24 (4) ◽  
pp. 334-341
Author(s):  
L. A. Bochkareva ◽  
L. V. Nedosugova ◽  
N. A. Petunina ◽  
M. Е. Теlnova ◽  
E. V. Goncharova
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Intracellular Signaling ◽  
Peripheral Tissues ◽  
Surface Receptors ◽  
Peripheral Insulin Resistance ◽  
Systemic Insulin Resistance ◽  
M1 Polarization ◽  
Anti Inflammatory

Inflammation plays a key role in the development and progression of type 2 diabetes (T2DM), a disease characterized by peripheral insulin resistance and systemic glucolipotoxicity. The main source of inflammation in the early stages of the disease is visceral adipose tissue (VT). Macrophages are innate immune cells that are present in all peripheral tissues, including VT. Violation of the response of VT (MT) macrophages to changes in the microenvironment underlies aberrant inflammation and the development of local and systemic insulin resistance. The inflammatory activation of macrophages is regulated at several levels: stimulation of cell surface receptors, intracellular signaling, transcription, and metabolic levels. Which are activated by the transformation of macrophages along the pro-inflammatory or anti-inflammatory pathways. Such polarization of macrophages in modern immunology is divided into classical anti-inflammatory M1 polarization and alternative anti-inflammatory M2 polarization of macrophages. The M1 / M2 ratio of macrophages in the process of inflammation ensures the resolution of inflammation at different stages of its development. The review considers the main mechanisms involved in VT inflammation and the development of insulin resistance in T2DM, supported with the participation of immunocompetent cells, M1 / M2, as well as growth factors and humoral immunity factors secreted during this process.

scholarly journals Vitamin D 3, osteoprotegerin and other hormonal and metabolic parameters in female patients with type 2 diabetes

2012 ◽  
Vol 9 (4) ◽  
pp. 23-27 ◽  
Author(s):  
A F Verbovoi ◽  
L A Sharonova ◽  
A V Kapishnikov ◽  
D V Demidova
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Vitamin D ◽  
Vitamin D3 ◽  
Metabolic Parameters ◽  
Female Patients ◽  
Vitamin D 3 ◽  
Diabetes And Obesity

The article presents the results of evaluation of vitamin D3, osteoprotegerin, carbohydrate and fat metabolic parameters in women with type 2 diabetes and obesity. The study subjects showed an increase of osteoprotegerin, decrease of vitamin D3, insulin resistance and compensatory hyperinsulinemia.

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