Transcriptional and post-translational regulation of adiponectin

2009 ◽  
Vol 425 (1) ◽  
pp. 41-52 ◽  
Author(s):  
Meilian Liu ◽  
Feng Liu
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Translational Regulation ◽  
Metabolic Disorders ◽  
Recent Progress ◽  
Serum Levels ◽  
High Molecular Mass ◽  
Adiponectin Gene ◽  
Underlying Mechanisms

Adiponectin is an adipose-tissue-derived hormone with anti-diabetic, anti-atherogenic and anti-inflammatory functions. Adiponectin circulates in the bloodstream in trimeric, hexameric and high-molecular-mass species, and different forms of adiponectin have been found to play distinct roles in the regulation of energy homoeostasis. The serum levels of adiponectin are negatively correlated with obesity and insulin resistance, yet the underlying mechanisms remain elusive. In the present review, we summarize recent progress made on the mechanisms regulating adiponectin gene transcription, multimerization and secretion. We also discuss the potential relevance of these studies to the development of new clinical therapy for insulin resistance, Type 2 diabetes and other obesity-related metabolic disorders.

scholarly journals Pathophysiological Molecular Mechanisms of Obesity: A Link between MAFLD and NASH with Cardiovascular Diseases

2021 ◽  
Vol 22 (21) ◽  
pp. 11629
Author(s):  
Jorge Gutiérrez-Cuevas ◽  
Arturo Santos ◽  
Juan Armendariz-Borunda
Keyword(s):  
Insulin Resistance ◽  
Metabolic Disorders ◽  
Molecular Mechanisms ◽  
Causes Of Death ◽  
Cardiovascular Prevention ◽  
Atherogenic Dyslipidemia ◽  
Metabolic Dysfunction ◽  
Systemic Insulin Resistance ◽  
Underlying Mechanisms

Obesity is now a worldwide epidemic ensuing an increase in comorbidities’ prevalence, such as insulin resistance, type 2 diabetes (T2D), metabolic dysfunction-associated fatty liver disease (MAFLD), nonalcoholic steatohepatitis (NASH), hypertension, cardiovascular disease (CVD), autoimmune diseases, and some cancers, CVD being one of the main causes of death in the world. Several studies provide evidence for an association between MAFLD and atherosclerosis and cardio-metabolic disorders, including CVDs such as coronary heart disease and stroke. Therefore, the combination of MAFLD/NASH is associated with vascular risk and CVD progression, but the underlying mechanisms linking MAFLD/NASH and CVD are still under investigation. Several underlying mechanisms may probably be involved, including hepatic/systemic insulin resistance, atherogenic dyslipidemia, hypertension, as well as pro-atherogenic, pro-coagulant, and pro-inflammatory mediators released from the steatotic/inflamed liver. MAFLD is strongly associated with insulin resistance, which is involved in its pathogenesis and progression to NASH. Insulin resistance is a major cardiovascular risk factor in subjects without diabetes. However, T2D has been considered the most common link between MAFLD/NASH and CVD. This review summarizes the evidence linking obesity with MAFLD, NASH, and CVD, considering the pathophysiological molecular mechanisms involved in these diseases. We also discuss the association of MAFLD and NASH with the development and progression of CVD, including structural and functional cardiac alterations, and pharmacological strategies to treat MAFLD/NASH and cardiovascular prevention.

scholarly journals Pathology, Risk Factors, and Oxidative Damage Related to Type 2 Diabetes-Mediated Alzheimer’s Disease and the Rescuing Effects of the Potent Antioxidant Anthocyanin

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Muhammad Sohail Khan ◽  
Muhammad Ikram ◽  
Tae Ju Park ◽  
Myeong Ok Kim
Keyword(s):  
Alzheimer’S Disease ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Alzheimer's Disease ◽  
Inflammatory Cytokines ◽  
Amyloid Beta ◽  
Acid Oxidation ◽  
Chronic Hyperglycemia ◽  
Underlying Mechanisms

The pathology and neurodegeneration in type 2 diabetes- (T2D-) mediated Alzheimer’s disease (AD) have been reported in several studies. Despite the lack of information regarding the basic underlying mechanisms involved in the development of T2D-mediated AD, some common features of the two conditions have been reported, such as brain atrophy, reduced cerebral glucose metabolism, and insulin resistance. T2D phenotypes such as glucose dyshomeostasis, insulin resistance, impaired insulin signaling, and systemic inflammatory cytokines have been shown to be involved in the progression of AD pathology by increasing amyloid-beta accumulation, tau hyperphosphorylation, and overall neuroinflammation. Similarly, oxidative stress, mitochondrial dysfunction, and the generation of advanced glycation end products (AGEs) and their receptor (RAGE) as a result of chronic hyperglycemia may serve as critical links between diabetes and AD. The natural dietary polyflavonoid anthocyanin enhances insulin sensitivity, attenuates insulin resistance at the level of the target tissues, inhibits free fatty acid oxidation, and abrogates the release of peripheral inflammatory cytokines in obese (prediabetic) individuals, which are responsible for insulin resistance, systemic hyperglycemia, systemic inflammation, brain metabolism dyshomeostasis, amyloid-beta accumulation, and neuroinflammatory responses. In this review, we have shown that obesity may induce T2D-mediated AD and assessed the recent therapeutic advances, especially the use of anthocyanin, against T2D-mediated AD pathology. Taken together, the findings of current studies may help elucidate a new approach for the prevention and treatment of T2D-mediated AD by using the polyflavonoid anthocyanin.

scholarly journals Disrupting phosphatase SHP2 in macrophages protects mice from high-fat diet-induced hepatic steatosis and insulin resistance by elevating IL-18 levels

2020 ◽  
Vol 295 (31) ◽  
pp. 10842-10856 ◽  
Author(s):  
Wen Liu ◽  
Ye Yin ◽  
Meijing Wang ◽  
Ting Fan ◽  
Yuyu Zhu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Hepatic Steatosis ◽  
High Fat Diet ◽  
Metabolic Disorders ◽  
Metabolic Diseases ◽  
Low Grade ◽  
High Fat ◽  
Caspase 1

Chronic low-grade inflammation plays an important role in the pathogenesis of type 2 diabetes. Src homology 2 domain-containing tyrosine phosphatase-2 (SHP2) has been reported to play diverse roles in different tissues during the development of metabolic disorders. We previously reported that SHP2 inhibition in macrophages results in increased cytokine production. Here, we investigated the association between SHP2 inhibition in macrophages and the development of metabolic diseases. Unexpectedly, we found that mice with a conditional SHP2 knockout in macrophages (cSHP2-KO) have ameliorated metabolic disorders. cSHP2-KO mice fed a high-fat diet (HFD) gained less body weight and exhibited decreased hepatic steatosis, as well as improved glucose intolerance and insulin sensitivity, compared with HFD-fed WT littermates. Further experiments revealed that SHP2 deficiency leads to hyperactivation of caspase-1 and subsequent elevation of interleukin 18 (IL-18) levels, both in vivo and in vitro. Of note, IL-18 neutralization and caspase-1 knockout reversed the amelioration of hepatic steatosis and insulin resistance observed in the cSHP2-KO mice. Administration of two specific SHP2 inhibitors, SHP099 and Phps1, improved HFD-induced hepatic steatosis and insulin resistance. Our findings provide detailed insights into the role of macrophagic SHP2 in metabolic disorders. We conclude that pharmacological inhibition of SHP2 may represent a therapeutic strategy for the management of type 2 diabetes.

scholarly journals Correlation between Blood Activin Levels and Clinical Parameters of Type 2 Diabetes

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Hui Wu ◽  
Michael Wu ◽  
Yi Chen ◽  
Carolyn A. Allan ◽  
David J. Phillips ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Glucose Tolerance ◽  
Fasting Glucose ◽  
Serum Levels ◽  
Activin A ◽  
Oral Glucose ◽  
Clinical Parameters ◽  
Model Assessment

Aims. Activins A and B, and their binding protein, follistatin, regulate glucose metabolism and inflammation. Consequently, their role in type 2 diabetes (T2D) was examined.Methods. Blood was taken from fasted participants (34 males; 58 females; 50–75 years) with diabetes or during an oral glucose tolerance test (OGTT). Clinical parameters were assessed, and blood assayed for activins, follistatin, and C-reactive protein.Results. Serum levels of activin A (93.3 ± 27.0 pg/mL, mean ± SD), B (81.8 ± 30.8 pg/mL), or follistatin (6.52 ± 3.15 ng/mL) were not different (P>0.05) between subjects with normal OGTT (n=39), impaired glucose tolerance and/or fasting glucose (n=17), or T2D (n=36). However, activin A and/or activin B were positively correlated with parameters of insulin resistance and T2D, including fasting glucose (P<0.001), fasting insulin (P=0.02), glycated hemoglobin (P=0.003), and homeostasis model assessment of insulin resistance (HOMA-IR;P<0.001). Follistatin was positively correlated with HOMA-IR alone (P=0.01).Conclusions. These data indicate that serum measurements of activin A, B, or follistatin cannot discriminate risk for T2D in individual patients, but the activins display a positive relationship with clinical parameters of the disease.

scholarly journals The insulin resistance indices: necessity and opportunities in type 2 diabetes mellitus management

2020 ◽  
Vol 96 (7) ◽  
pp. 529-535
Author(s):  
Yu. A. Sorokina ◽  
O. V. Zanozina ◽  
A. D. Postnikova
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Clinical Practice ◽  
Glycemic Control ◽  
Metabolic Disorders ◽  
Glycosylated Hemoglobin ◽  
Tissue Sensitivity

The article provides a review of the literature on the possibilities of using various indices of insulin resistance in type 2 diabetes (T2DM) treatment. The main mechanisms of insulin resistance and its role in the formation of type 2 diabetes mellitus and other metabolic disorders are described. The main indices of insulin resistance, used in real clinical practice nowadays, are considered. Methods of their calculation are given. The effect of metformin and incretin active medications on insulin resistance is described. It was shown that the combination of these medications improves tissue sensitivity to insulin in patients with T2DM. Standard indicators for assessing glycemic control, such as fasting glucose and glycosylated hemoglobin (HbA1c), do not reflect the patient’s lipid metabolism. The use of insulin resistance assessment indices in patients with type 2 diabetes mellitus allows both, exercising glycemic control, and the metabolic disorders, often associated with carbohydrate metabolism disorders, monitoring. Using insulin resistance indices, it is possible to select the optimal treatment regimen for type 2 diabetes mellitus for a particular patient, to predict and evaluate the effectiveness of treatment in dynamics. Simple, generally available laboratory indicators and anthropometric data are used to calculate the indices of insulin resistance, and they are easy to measure. In this regard, the use of insulin resistance indices is possible in routine clinical practice.

scholarly journals Intersections between copper, β-arrestin-1, calcium, FBXW7, CD17, insulin resistance and atherogenicity mediate depression and anxiety due to type 2 diabetes mellitus: a nomothetic network approach.

2021 ◽  
Author(s):  
Hussein K Al-Hakeim ◽  
Shaymaa Al-Hamami ◽  
Ghoufran Jawad ◽  
Michael Maes
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Rating Scales ◽  
Serum Levels ◽  
Depression And Anxiety ◽  
Affective Symptoms ◽  
Copper Zinc

Background: Type 2 diabetes mellitus (T2DM) is frequently accompanied by affective disorders with a prevalence of comorbid depression of around 25%. Nevertheless, the biomarkers of affective symptoms including depression and anxiety due to T2DM are not well established. Aims: This study was conducted to delineate the serum biomarkers predicting affective symptoms due to T2DM above and beyond the effects of insulin resistance and atherogenicity. Methods: The present study delineated the effects of serum levels of copper, zinc, β-arrestin-1, FBXW7, lactosylceramide (LacCer), serotonin, albumin, calcium, magnesium, IR and atherogenicity on severity of depression and anxiety in 58 men with T2DM and 30 healthy male controls. Severity of affective symptoms was assessed using the Hamilton Depression and Anxiety rating scales. Results: We found that 61.7% of the variance in affective symptoms was explained by the multivariate regression on copper, β-arrestin-1, calcium, and insulin resistance coupled with atherogenicity, while 44.4% of the variance in the latter was explained by copper, β-arrestin-1, LacCer (all positively) and calcium and FBXW7 (both negatively). Copper and LacCer (positive) and calcium and BXW7 (inverse) had significant specific indirect effects on affective symptoms which were mediated by insulin resistance and atherogenicity. Copper, β-arrestin-1, and calcium were associated with affective symptoms above and beyond the effects of insulin resistance and atherogenicity. Discussion: T2DM and affective symptoms share common pathways namely increased atherogenicity, insulin resistance, copper, and β-arrestin-1, and lowered calcium, whereas copper, β-arrestin-1, calcium, LacCer, and FBXW7 may modulate depression and anxiety symptoms by affecting T2DM.

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.

Effects and significance of estradiol in men

2014 ◽  
Vol 155 (23) ◽  
pp. 891-896 ◽  
Author(s):  
Judit Tőke ◽  
Gábor Czirják ◽  
Attila Bezzegh ◽  
Barna Vásárhelyi ◽  
Károly Rácz ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Metabolic Disorders ◽  
Therapeutic Strategies ◽  
Cardiovascular Disorders ◽  
Androgen Deficiency ◽  
Men And Women ◽  
Estradiol Levels

The most important estrogen is estradiol in both men and women. In men elevated estradiol levels and associated metabolic disorders have been implicated in the development of common diseases including cardiovascular disorders, insulin resistance and type 2 diabetes mellitus, as increased estradiol associated with decreased testosterone levels increases the risk of these diseases. In this review the authors summarize the causes and consequences of androgen deficiency and estradiol excess, and they review recent studies on potential therapeutic strategies to correct increased estradiol levels in men. Orv. Hetil., 2014, 155(23), 891–896.

scholarly journals Intersections between Copper, β-Arrestin-1, Calcium, FBXW7, CD17, Insulin Resistance and Atherogenicity Mediate Depression and Anxiety Due to Type 2 Diabetes Mellitus: A Nomothetic Network Approach

2021 ◽  
Author(s):  
Hussein Al-Hakeim ◽  
Hadi Hadi ◽  
Ghoufran Jawad ◽  
Michael Maes
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Serum Levels ◽  
Depression And Anxiety ◽  
Affective Symptoms ◽  
Calcium Magnesium ◽  
Copper Zinc

Type 2 diabetes mellitus (T2DM) is frequently accompanied by affective disorders with a prevalence of comorbid depression of around 25%. Nevertheless, the biomarkers of affective symptoms including depression and anxiety due to T2DM are not well established.Aims: This study was conducted to delineate the serum biomarkers predicting affective symptoms due to T2DM above and beyond the effects of insulin resistance and atherogenicity. Methods: The present study delineated the effects of serum levels of copper, zinc, &beta;-arrestin-1, FBXW7, lactosylceramide (LacCer), serotonin, albumin, calcium, magnesium, IR and atherogenicity on severity of depression and anxiety in 58 men with T2DM and 30 healthy male controls. Severity of affective symptoms was assessed using the Hamilton Depression and Anxiety rating scales.Results: We found that 61.7% of the variance in affective symptoms was explained by the multivariate regression on copper, &beta;-arrestin-1, calcium, and insulin resistance coupled with atherogenicity, while 44.4% of the variance in the latter was explained by copper, &beta;-arrestin-1, LacCer (all positively) and calcium and FBXW7 (both negatively). Copper and LacCer (positive) and calcium and BXW7 (inverse) had significant specific indirect effects on affective symptoms which were mediated by insulin resistance and atherogenicity. Copper, &beta;-arrestin-1, and calcium were associated with affective symptoms above and beyond the effects of insulin resistance and atherogenicity.Discussion: T2DM and affective symptoms share common pathways namely increased atherogenicity, insulin resistance, copper, and &beta;-arrestin-1, and lowered calcium, whereas copper, &beta;-arrestin-1, calcium, LacCer, and FBXW7 may modulate depression and anxiety symptoms by affecting T2DM.

Sign in / Sign up

Export Citation Format

Share Document