Insulin Resistance: From Naive Understanding of Genetics to the Complexity of Endocrine and Metabolic Diseases

2005 ◽  
Vol 1 (3) ◽  
pp. 341-350
Author(s):  
Florin Grigorescu
Keyword(s):  
Insulin Resistance ◽  
Metabolic Diseases

Folate and vitamin B-12 deficiencies additively impaired memory function and disturbed the gut microbiota in amyloid-β infused rats

2019 ◽  
pp. 1-13 ◽  
Author(s):  
Sunmin Park ◽  
Sunna Kang ◽  
Da Sol Kim
Keyword(s):  
Insulin Resistance ◽  
Gut Microbiota ◽  
Insulin Signaling ◽  
Gut Microbiome ◽  
Metabolic Diseases ◽  
Memory Function ◽  
Amyloid Β ◽  
Impaired Memory ◽  
Ca1 Region ◽  
Folate And Vitamin B12

Abstract. Folate and vitamin B12(V-B12) deficiencies are associated with metabolic diseases that may impair memory function. We hypothesized that folate and V-B12 may differently alter mild cognitive impairment, glucose metabolism, and inflammation by modulating the gut microbiome in rats with Alzheimer’s disease (AD)-like dementia. The hypothesis was examined in hippocampal amyloid-β infused rats, and its mechanism was explored. Rats that received an amyloid-β(25–35) infusion into the CA1 region of the hippocampus were fed either control(2.5 mg folate plus 25 μg V-B12/kg diet; AD-CON, n = 10), no folate(0 folate plus 25 μg V-B12/kg diet; AD-FA, n = 10), no V-B12(2.5 mg folate plus 0 μg V-B12/kg diet; AD-V-B12, n = 10), or no folate plus no V-B12(0 mg folate plus 0 μg V-B12/kg diet; AD-FAB12, n = 10) in high-fat diets for 8 weeks. AD-FA and AD-VB12 exacerbated bone mineral loss in the lumbar spine and femur whereas AD-FA lowered lean body mass in the hip compared to AD-CON(P < 0.05). Only AD-FAB12 exacerbated memory impairment by 1.3 and 1.4 folds, respectively, as measured by passive avoidance and water maze tests, compared to AD-CON(P < 0.01). Hippocampal insulin signaling and neuroinflammation were attenuated in AD-CON compared to Non-AD-CON. AD-FAB12 impaired the signaling (pAkt→pGSK-3β) and serum TNF-α and IL-1β levels the most among all groups. AD-CON decreased glucose tolerance by increasing insulin resistance compared to Non-AD-CON. AD-VB12 and AD-FAB12 increased insulin resistance by 1.2 and 1.3 folds, respectively, compared to the AD-CON. AD-CON and Non-AD-CON had a separate communities of gut microbiota. The relative counts of Bacteroidia were lower and those of Clostridia were higher in AD-CON than Non-AD-CON. AD-FA, but not V-B12, separated the gut microbiome community compared to AD-CON and AD-VB12(P = 0.009). In conclusion, folate and B-12 deficiencies impaired memory function by impairing hippocampal insulin signaling and gut microbiota in AD rats.

scholarly journals Adipocyte, Immune Cells, and miRNA Crosstalk: A Novel Regulator of Metabolic Dysfunction and Obesity

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1004
Author(s):  
Sonia Kiran ◽  
Vijay Kumar ◽  
Santosh Kumar ◽  
Robert L Price ◽  
Udai P. Singh
Keyword(s):  
Insulin Resistance ◽  
Immune Response ◽  
T Cells ◽  
Immune Cells ◽  
Metabolic Diseases ◽  
Liver Disorder ◽  
Low Grade ◽  
Peripheral Tissues ◽  
Nonalcoholic Fatty Liver ◽  
Cytokines And Chemokines

Obesity is characterized as a complex and multifactorial excess accretion of adipose tissue (AT) accompanied with alterations in the immune response that affects virtually all age and socioeconomic groups around the globe. The abnormal accumulation of AT leads to several metabolic diseases, including nonalcoholic fatty liver disorder (NAFLD), low-grade inflammation, type 2 diabetes mellitus (T2DM), cardiovascular disorders (CVDs), and cancer. AT is an endocrine organ composed of adipocytes and immune cells, including B-Cells, T-cells and macrophages. These immune cells secrete various cytokines and chemokines and crosstalk with adipokines to maintain metabolic homeostasis and low-grade chronic inflammation. A novel form of adipokines, microRNA (miRs), is expressed in many developing peripheral tissues, including ATs, T-cells, and macrophages, and modulates the immune response. miRs are essential for insulin resistance, maintaining the tumor microenvironment, and obesity-associated inflammation (OAI). The abnormal regulation of AT, T-cells, and macrophage miRs may change the function of different organs including the pancreas, heart, liver, and skeletal muscle. Since obesity and inflammation are closely associated, the dysregulated expression of miRs in inflammatory adipocytes, T-cells, and macrophages suggest the importance of miRs in OAI. Therefore, in this review article, we have elaborated the role of miRs as epigenetic regulators affecting adipocyte differentiation, immune response, AT browning, adipogenesis, lipid metabolism, insulin resistance (IR), glucose homeostasis, obesity, and metabolic disorders. Further, we will discuss a set of altered miRs as novel biomarkers for metabolic disease progression and therapeutic targets for obesity.

Intramyocellular fat storage in metabolic diseases

2016 ◽  
Vol 26 (1) ◽  
Author(s):  
Claire Laurens ◽  
Cedric Moro
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Metabolic Diseases ◽  
Recent Literature ◽  
Lipid Storage ◽  
Muscle Lipid ◽  
The Past ◽  
Skeletal Muscle Lipid ◽  
Ectopic Lipid Storage

AbstractOver the past decades, obesity and its metabolic co-morbidities such as type 2 diabetes (T2D) developed to reach an endemic scale. However, the mechanisms leading to the development of T2D are still poorly understood. One main predictor for T2D seems to be lipid accumulation in “non-adipose” tissues, best known as ectopic lipid storage. A growing body of data suggests that these lipids may play a role in impairing insulin action in metabolic tissues, such as liver and skeletal muscle. This review aims to discuss recent literature linking ectopic lipid storage and insulin resistance, with emphasis on lipid deposition in skeletal muscle. The link between skeletal muscle lipid content and insulin sensitivity, as well as the mechanisms of lipid-induced insulin resistance and potential therapeutic strategies to alleviate lipotoxic lipid pressure in skeletal muscle will be discussed.

scholarly journals Effects of 10-Week Concurrent Training on Insulin Resistance and the Serum Levels of Vaspin and Visfatin in Overweight Females

2019 ◽  
Vol 25 (3) ◽  
pp. 146-157
Author(s):  
Abdolreza Kazemi ◽  
◽  
Sareh Mahalati ◽  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Diseases ◽  
Intervention Group ◽  
Serum Levels ◽  
Analysis Of Covariance ◽  
Concurrent Training ◽  
Improve Insulin Sensitivity ◽  
Glucose Levels ◽  
Kerman City ◽  
Training Protocol

Aims: The present study investigated the effects of a 10-week concurrent training on the serum levels of vaspin and visfatin in overweight females. Methods & Materials: Twenty-four over-weight females from Kerman City, Iran (Mean±SD age: 11.23±0.62 years; Mean±SD weight: 64.83±2.70kg; Mean±SD BMI: 27.97±0.47 kg/m2) were randomly assigned into the control and concurrent training groups. The intervention group performed the training protocol as follows: endurance training: 65-85% of Vo2 max for 20 minutes per session, and resistance training: 50-60% of One Repetition Maximum (1RM) for 30 minutes per session and 3 days a week for 10 weeks. Fasting plasma vaspin, visfatin, and insulin levels were measured by ELISA method. To analyze the data, Analysis of Covariance (ANCOVA) was used. Findings: Performing 10 weeks of concurrent training significantly decreased vaspin and visfatin plasma levels, and insulin resistance resting levels (P≤0.05); however, there was no significant decrease in glucose levels. Conclusion: Concurrent training can decrease insulin resistance, probably by reducing vaspin and visfatin in overweight females. Therefore, it is suggested that overweight females use concurrent training to improve insulin sensitivity and prevent metabolic diseases.

scholarly journals Exposure to the Widely Used Pyrethroid Pesticide Deltamethrin, Does Not Exacerbate High Fat Diet Induced Obesity or Insulin Resistance in C57BL/6J Mice

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A45-A46
Author(s):  
Evangelia Evelyn Tsakiridis ◽  
Marisa Morrow ◽  
Andrea Llanos ◽  
Bo Wang ◽  
Alison Holloway ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glycemic Control ◽  
Metabolic Diseases ◽  
Uncoupling Protein ◽  
Diet Induced Obesity ◽  
Brown Adipose ◽  
Pyrethroid Pesticide ◽  
First Time

Abstract Deltamethrin is a commonly used pesticide for the control of mosquito populations. Despite widespread use, the effects of deltamethrin on adiposity and glucose homeostasis have been equivocal with some studies showing increased, decreased and no effect on adiposity and glycemic control. However, no study to date has investigated the effect of deltamethrin in mice housed at thermoneutral temperatures, which is important for modelling metabolic diseases in rodents due to reduced thermal stress and constitutive activation of brown adipose tissue. In the current study we demonstrate for the first time that deltamethrin reduces uncoupling protein-1 expression in brown adipocytes cultured in vitro at concentrations as low as 1pm. Meanwhile, in-vivo deltamethrin does not appear to alter glycemic control or promote adiposity at exposures equivalent to 0.01, 0.1 or 1.0 mg/kg/day. Together, our study demonstrates environmentally relevant exposure to deltamethrin does not exacerbate diet induced obesity or insulin resistance.

scholarly journals Novel Grb14-Mediated Cross Talk between Insulin and p62/Nrf2 Pathways Regulates Liver Lipogenesis and Selective Insulin Resistance

2016 ◽  
Vol 36 (16) ◽  
pp. 2168-2181 ◽  
Author(s):  
Lucie Popineau ◽  
Lucille Morzyglod ◽  
Nadège Carré ◽  
Michèle Caüzac ◽  
Pascale Bossard ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Receptor ◽  
Metabolic Diseases ◽  
De Novo ◽  
Liver Steatosis ◽  
Growth Factor Receptor ◽  
Glucose Production ◽  
Acid Synthesis ◽  
Related Factor ◽  
Insulin Resistant

A long-standing paradox in the pathophysiology of metabolic diseases is the selective insulin resistance of the liver. It is characterized by a blunted action of insulin to reduce glucose production, contributing to hyperglycemia, whilede novolipogenesis remains insulin sensitive, participating in turn to hepatic steatosis onset. The underlying molecular bases of this conundrum are not yet fully understood. Here, we established a model of selective insulin resistance in mice by silencing an inhibitor of insulin receptor catalytic activity, the growth factor receptor binding protein 14 (Grb14) in liver. Indeed, Grb14 knockdown enhanced hepatic insulin signaling but also dramatically inhibitedde novofatty acid synthesis. In the liver of obese and insulin-resistant mice, downregulation of Grb14 markedly decreased blood glucose and improved liver steatosis. Mechanistic analyses showed that upon Grb14 knockdown, the release of p62/sqstm1, a partner of Grb14, activated the transcription factor nuclear factor erythroid-2-related factor 2 (Nrf2), which in turn repressed the lipogenic nuclear liver X receptor (LXR). Our study reveals that Grb14 acts as a new signaling node that regulates lipogenesis and modulates insulin sensitivity in the liver by acting at a crossroad between the insulin receptor and the p62-Nrf2-LXR signaling pathways.

scholarly journals Elevated Circulating Fetuin-B Levels Are Associated with Insulin Resistance and Reduced by GLP-1RA in Newly Diagnosed PCOS Women

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Mani Mokou ◽  
Shan Yang ◽  
Bin Zhan ◽  
Shan Geng ◽  
Kejia Li ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Blood Glucose ◽  
Glucose Tolerance ◽  
Metabolic Diseases ◽  
Polycystic Ovary ◽  
Fasting Blood Glucose ◽  
Resistance Index ◽  
Oral Glucose ◽  
Healthy Women ◽  
Tnf Α

Background. Previous studies have suggested that Fetuin-B seems to be a secreted adipokine related to metabolic diseases. However, the results have been inconsistent. Here, our objective is to investigate the changes in circulating Fetuin-B levels in women with polycystic ovary syndrome (PCOS) and analyze the association of Fetuin-B and insulin resistance (IR). Methods. The current study is comprised of a cross-sectional study and a series of interventional studies. Oral glucose tolerance test (OGTT) and euglycemic-hyperinsulinemic clamp (EHC) were engaged to assess glucose tolerance and insulin sensitivity. Serum Fetuin-B levels were determined by ELISA. Results. Serum Fetuin-B and TNF-α levels were markedly increased in women with PCOS compared to healthy women. Circulating Fetuin-B was positively associated with body mass index, waist-to-hip ratio, the percentage of body fat (FAT%), systolic blood pressure, triglyceride, low-density lipoprotein cholesterol, fasting blood glucose, 2 h blood glucose after glucose overload, fasting insulin, 2 h insulin after glucose overload, HOMA-insulin resistance index (HOMA-IR), the area under the curve for insulin (AUCi), AUCg, and TNF-α, while negatively associated with M value and follicular stimulating hormone (FSH). During the EHC, Fetuin-B levels were found to be significantly increased in PCOS women. After a glucose challenge, serum Fetuin-B levels in healthy women were significantly increased. Lipid infusion reduced serum Fetuin-B levels in 30 healthy subjects. After six months of glucagon-like peptide-1 receptor agonist (GLP-1RA) intervention, serum Fetuin-B concentrations in PCOS women markedly decreased following ameliorated IR. Conclusion. Our results indicate that Fetuin-B may be a biomarker of IR in individuals with PCOS. This trial is registered with ChiCTR-IIR-16007901.

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.

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