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Nutrients, Bioactives and Insulin Resistance

A special issue of Nutrients (ISSN 2072-6643).

Deadline for manuscript submissions: closed (31 January 2018) | Viewed by 112236

Special Issue Editors


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Guest Editor
1. Department of Food and Human Nutritional Sciences, University of Manitoba, Winnipeg, MB R3T 2N2, Canada
2. Canadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Hospital Albrechtsen Research Centre, Winnipeg, MB R2H 2A6, Canada
3. Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, MB R3E 0W2, Canada
Interests: physiology; metabolism; insulin resistance; insulin signalling; endothelial dysfunction; hypertension; atherosclerosis; obesity; lipid mediators; clinical trials

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Guest Editor
Department of Human Nutritional Sciences, Faculty of Agriculture and Food Science, University of Manitoba, and Canadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Albrechtsen Research Centre, 351 Tache Avenue, Winnipeg, MB, Canada R2H 2A6
Interests: nutrition; dietary interventions; obesity; diabetes; metabolic syndrome; adipocyte dysfunction; hepatic steatosis; immune defense; cell signaling
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Our understanding of insulin resistance remains limited, even though this condition is a considerable burden on human health. Diet has a major role in its onset and eventual progression to diabetes, however, at the same time, it is recognized that dietary constituents may provide a means to intervene, thus reducing the morbidity and mortality that stem from insulin resistance. Information regarding the ability of nutrients and bioactive compounds to modulate insulin resistance may provide novel therapeutic approaches for intervention. However, this can only happen if we know which compounds exhibit biological activity in an achievable dose, thus establishing which of the many components in our diet have relevance, will only occur if we know function, as well as their potency. Accumulation of the necessary knowledge could enable translation to the clinic through the development of novel functional foods or nutraceuticals, or through the formulation of new dietary guidelines to assist those who are insulin resistant.

Developing new paradigms to explain the effects of diet on glucose and lipid metabolism in the context of insulin resistance could lead to novel insights regarding approaches to intervene in these processes. This Special Issue will, thus, include original research and scientific perspectives on the relationship between insulin resistance and dietary constituents that may promote or prevent progression of this condition to diabetes. Mechanistic insights defining the contribution of diet to the occurrence and management of insulin resistance will provide additional details to our understanding of the clinical implications of insulin resistance.

Dr. Peter Zahradka
Dr. Carla G. Taylor
Guest Editors

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Keywords

  • insulin resistance
  • obesity
  • diabetes
  • glycemia
  • lipidemia
  • macronutrients
  • micronutrients
  • dietary bioactive compounds
  • signal transduction
  • gene expression

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Published Papers (9 papers)

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Research

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15 pages, 2819 KiB  
Article
Lactobacillus plantarum Strain Ln4 Attenuates Diet-Induced Obesity, Insulin Resistance, and Changes in Hepatic mRNA Levels Associated with Glucose and Lipid Metabolism
by Eunjung Lee, So-Ra Jung, So-Young Lee, Na-Kyoung Lee, Hyun-Dong Paik and Seong-Il Lim
Nutrients 2018, 10(5), 643; https://doi.org/10.3390/nu10050643 - 19 May 2018
Cited by 122 | Viewed by 11072
Abstract
The prevalence of obesity and associated metabolic disorders, including diabetes and cardiovascular disease, is rapidly becoming a severe global health problem. Recent reports have suggested that the alteration of the gut ecosystem through the consumption of probiotics and fermented foods, such as yogurt [...] Read more.
The prevalence of obesity and associated metabolic disorders, including diabetes and cardiovascular disease, is rapidly becoming a severe global health problem. Recent reports have suggested that the alteration of the gut ecosystem through the consumption of probiotics and fermented foods, such as yogurt and Kimchi, can significantly impact obesity and Type 2 diabetes (T2D)-related biomarkers. In this study, we screened over 400 strains of lactic acid bacteria (LAB) that were isolated from fermented foods to identify potent anti-obesogenic and diabetic probiotics in vitro. Of the strains tested, Lactobacillus plantarum Ln4 (Ln4), which was obtained from napa cabbage kimchi, significantly reduced lipid accumulation and stimulated glucose uptake in 3T3-L1 adipocytes. Oral administration of Ln4 reduced weight gain and epididymal fat mass in mice fed on a high-fat diet (HFD). Total plasma triglyceride level was significantly lower in mice that were treated Ln4 as compared with mice fed HFD. The protein levels of adipokines such as C-reactive protein (CRP), insulin-like growth factor binding proteins-3 (IGFBP-3), and monocyte chemoattractant protein-1 (MCP-1) decreased in white adipose tissues of Ln4-treated mice. Furthermore, these mice exhibited a significant reduction of insulin resistance index (HOMA-IR) and the improvement of glucose tolerance (OGTT) and insulin response (ITT) following Ln4 administration. This was associated with changes in several hepatic gene expressions (increased mRNA levels of IRS2, Akt2, AMPK, LPL, and reduced CD36) that regulate glucose and lipid metabolism. Taken together, these results indicate that in vitro and in vivo Ln4 treatment attenuates diet-induced obesity and T2D biomarkers, highlighting the potential of Ln4 as a therapeutic probiotic agent for metabolic disorders. Full article
(This article belongs to the Special Issue Nutrients, Bioactives and Insulin Resistance)
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12 pages, 1394 KiB  
Article
Anti-Diabetic Effects and Anti-Inflammatory Effects of Laminaria japonica and Hizikia fusiforme in Skeletal Muscle: In Vitro and In Vivo Model
by Sae-ym Kang, Eunyoung Kim, Inhae Kang, Myoungsook Lee and Yunkyoung Lee
Nutrients 2018, 10(4), 491; https://doi.org/10.3390/nu10040491 - 16 Apr 2018
Cited by 46 | Viewed by 6219
Abstract
Laminaria japonica (LJ) and Hizikia fusiforme (HF) are brown seaweeds known to have various health-promoting effects. In this study, we investigated the anti-diabetic effects and possible mechanism(s) of LJ and HF by using both in vitro and in vivo [...] Read more.
Laminaria japonica (LJ) and Hizikia fusiforme (HF) are brown seaweeds known to have various health-promoting effects. In this study, we investigated the anti-diabetic effects and possible mechanism(s) of LJ and HF by using both in vitro and in vivo models. C2C12 myotubes, mouse-derived skeletal muscle cells, treated with LF or HF extracts were used for the in vitro model, and muscle tissues from C57BL/6N mice fed a high-fat diet supplemented with 5% LF or HF for 16 weeks were used for the in vivo model. Although both the LF and HF extracts significantly inhibited α-glucosidase activity in a dose-dependent manner, the HF extract had a superior α-glucosidase inhibition than the LF extract. In addition, glucose uptake was significantly increased by LJ- and HF-treated groups when compared to the control group. Phosphorylation of protein kinase B and AMP-activated protein kinase was induced by LJ and HF in both the vivo and in vitro skeletal muscle models. Furthermore, LJ and HF significantly decreased tumor necrosis factor-α whereas both extracts increased interleukin (IL)-6 and IL-10 production in lipopolysaccharide-stimulated C2C12 myotubes. Taken together, these findings imply that the brown seaweeds LJ and HF could be useful therapeutic agents to attenuate muscle insulin resistance due to diet-induced obesity and its associated inflammation. Full article
(This article belongs to the Special Issue Nutrients, Bioactives and Insulin Resistance)
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2233 KiB  
Article
Cyanidin Stimulates Insulin Secretion and Pancreatic β-Cell Gene Expression through Activation of l-type Voltage-Dependent Ca2+ Channels
by Tanyawan Suantawee, Sara T. Elazab, Walter H. Hsu, Shaomian Yao, Henrique Cheng and Sirichai Adisakwattana
Nutrients 2017, 9(8), 814; https://doi.org/10.3390/nu9080814 - 28 Jul 2017
Cited by 30 | Viewed by 6665
Abstract
Cyanidin is a natural anthocyanidin present in fruits and vegetables with anti-diabetic properties including stimulation of insulin secretion. However, its mechanism of action remains unknown. In this study, we elucidated the mechanisms of cyanidin for stimulatory insulin secretion from pancreatic β-cells. Rat pancreatic [...] Read more.
Cyanidin is a natural anthocyanidin present in fruits and vegetables with anti-diabetic properties including stimulation of insulin secretion. However, its mechanism of action remains unknown. In this study, we elucidated the mechanisms of cyanidin for stimulatory insulin secretion from pancreatic β-cells. Rat pancreatic β-cells INS-1 were used to investigate the effects of cyanidin on insulin secretion, intracellular Ca2+ signaling, and gene expression. We detected the presence of cyanidin in the intracellular space of β-cells. Cyanidin stimulated insulin secretion and increased intracellular Ca2+ signals in a concentration-dependent manner. The Ca2+ signals were abolished by nimodipine, an l-type voltage-dependent Ca2+ channel (VDCC) blocker or under extracellular Ca2+ free conditions. Stimulation of cells with cyanidin activated currents typical for VDCCs and up-regulated the expression of glucose transporter 2 (GLUT2), Kir6.2, and Cav1.2 genes. Our findings indicate that cyanidin diffuses across the plasma membrane, leading to activation of l-type VDCCs. The increase in intracellular Ca2+ stimulated insulin secretion and the expression of genes involved in this process. These findings suggest that cyanidin could be used as a promising agent to stimulate insulin secretion. Full article
(This article belongs to the Special Issue Nutrients, Bioactives and Insulin Resistance)
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Review

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21 pages, 1065 KiB  
Review
Capsaicin in Metabolic Syndrome
by Sunil K. Panchal, Edward Bliss and Lindsay Brown
Nutrients 2018, 10(5), 630; https://doi.org/10.3390/nu10050630 - 17 May 2018
Cited by 114 | Viewed by 21059
Abstract
Capsaicin, the major active constituent of chilli, is an agonist on transient receptor potential vanilloid channel 1 (TRPV1). TRPV1 is present on many metabolically active tissues, making it a potentially relevant target for metabolic interventions. Insulin resistance and obesity, being the major components [...] Read more.
Capsaicin, the major active constituent of chilli, is an agonist on transient receptor potential vanilloid channel 1 (TRPV1). TRPV1 is present on many metabolically active tissues, making it a potentially relevant target for metabolic interventions. Insulin resistance and obesity, being the major components of metabolic syndrome, increase the risk for the development of cardiovascular disease, type 2 diabetes, and non-alcoholic fatty liver disease. In vitro and pre-clinical studies have established the effectiveness of low-dose dietary capsaicin in attenuating metabolic disorders. These responses of capsaicin are mediated through activation of TRPV1, which can then modulate processes such as browning of adipocytes, and activation of metabolic modulators including AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor α (PPARα), uncoupling protein 1 (UCP1), and glucagon-like peptide 1 (GLP-1). Modulation of these pathways by capsaicin can increase fat oxidation, improve insulin sensitivity, decrease body fat, and improve heart and liver function. Identifying suitable ways of administering capsaicin at an effective dose would warrant its clinical use through the activation of TRPV1. This review highlights the mechanistic options to improve metabolic syndrome with capsaicin. Full article
(This article belongs to the Special Issue Nutrients, Bioactives and Insulin Resistance)
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33 pages, 614 KiB  
Review
Dietary Flavonoids in the Prevention of T2D: An Overview
by Hana Alkhalidy, Yao Wang and Dongmin Liu
Nutrients 2018, 10(4), 438; https://doi.org/10.3390/nu10040438 - 31 Mar 2018
Cited by 89 | Viewed by 10229
Abstract
Type 2 diabetes (T2D) is a progressive metabolic disease that is increasing in prevalence globally. It is well established that insulin resistance (IR) and a progressive decline in functional β-cell mass are hallmarks of developing T2D. Obesity is a leading pathogenic factor for [...] Read more.
Type 2 diabetes (T2D) is a progressive metabolic disease that is increasing in prevalence globally. It is well established that insulin resistance (IR) and a progressive decline in functional β-cell mass are hallmarks of developing T2D. Obesity is a leading pathogenic factor for developing IR. Constant IR will progress to T2D when β-cells are unable to secret adequate amounts of insulin to compensate for decreased insulin sensitivity. Recently, a considerable amount of research has been devoted to identifying naturally occurring anti-diabetic compounds that are abundant in certain types of foods. Flavonoids are a group of polyphenols that have drawn great interest for their various health benefits. Results from many clinical and animal studies demonstrate that dietary intake of flavonoids might be helpful in preventing T2D, although cellular and molecular mechanisms underlying these effects are still not completely understood. This review discusses our current understanding of the pathophysiology of T2D and highlights the potential anti-diabetic effects of flavonoids and mechanisms of their actions. Full article
(This article belongs to the Special Issue Nutrients, Bioactives and Insulin Resistance)
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28 pages, 962 KiB  
Review
Rebelling against the (Insulin) Resistance: A Review of the Proposed Insulin-Sensitizing Actions of Soybeans, Chickpeas, and Their Bioactive Compounds
by Jaime L. Clark, Carla G. Taylor and Peter Zahradka
Nutrients 2018, 10(4), 434; https://doi.org/10.3390/nu10040434 - 30 Mar 2018
Cited by 27 | Viewed by 12047
Abstract
Insulin resistance is a major risk factor for diseases such as type 2 diabetes and metabolic syndrome. Current methods for management of insulin resistance include pharmacological therapies and lifestyle modifications. Several clinical studies have shown that leguminous plants such as soybeans and pulses [...] Read more.
Insulin resistance is a major risk factor for diseases such as type 2 diabetes and metabolic syndrome. Current methods for management of insulin resistance include pharmacological therapies and lifestyle modifications. Several clinical studies have shown that leguminous plants such as soybeans and pulses (dried beans, dried peas, chickpeas, lentils) are able to reduce insulin resistance and related type 2 diabetes parameters. However, to date, no one has summarized the evidence supporting a mechanism of action for soybeans and pulses that explains their ability to lower insulin resistance. While it is commonly assumed that the biological activities of soybeans and pulses are due to their antioxidant activities, these bioactive compounds may operate independent of their antioxidant properties and, thus, their ability to potentially improve insulin sensitivity via alternative mechanisms needs to be acknowledged. Based on published studies using in vivo and in vitro models representing insulin resistant states, the proposed mechanisms of action for insulin-sensitizing actions of soybeans, chickpeas, and their bioactive compounds include increasing glucose transporter-4 levels, inhibiting adipogenesis by down-regulating peroxisome proliferator-activated receptor-γ, reducing adiposity, positively affecting adipokines, and increasing short-chain fatty acid-producing bacteria in the gut. Therefore, this review will discuss the current evidence surrounding the proposed mechanisms of action for soybeans and certain pulses, and their bioactive compounds, to effectively reduce insulin resistance. Full article
(This article belongs to the Special Issue Nutrients, Bioactives and Insulin Resistance)
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20 pages, 4037 KiB  
Review
Lysophosphatidic Acid Signaling in Obesity and Insulin Resistance
by Kenneth D’Souza, Geena V. Paramel and Petra C. Kienesberger
Nutrients 2018, 10(4), 399; https://doi.org/10.3390/nu10040399 - 23 Mar 2018
Cited by 56 | Viewed by 9853
Abstract
Although simple in structure, lysophosphatidic acid (LPA) is a potent bioactive lipid that profoundly influences cellular signaling and function upon binding to G protein-coupled receptors (LPA1-6). The majority of circulating LPA is produced by the secreted enzyme autotaxin (ATX). Alterations in LPA signaling, [...] Read more.
Although simple in structure, lysophosphatidic acid (LPA) is a potent bioactive lipid that profoundly influences cellular signaling and function upon binding to G protein-coupled receptors (LPA1-6). The majority of circulating LPA is produced by the secreted enzyme autotaxin (ATX). Alterations in LPA signaling, in conjunction with changes in autotaxin (ATX) expression and activity, have been implicated in metabolic and inflammatory disorders including obesity, insulin resistance, and cardiovascular disease. This review summarizes our current understanding of the sources and metabolism of LPA with focus on the influence of diet on circulating LPA. Furthermore, we explore how the ATX-LPA pathway impacts obesity and obesity-associated disorders, including impaired glucose homeostasis, insulin resistance, and cardiovascular disease. Full article
(This article belongs to the Special Issue Nutrients, Bioactives and Insulin Resistance)
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20 pages, 1932 KiB  
Review
Omega-3 Fatty Acids and Insulin Resistance: Focus on the Regulation of Mitochondria and Endoplasmic Reticulum Stress
by Marilena Lepretti, Stefania Martucciello, Mario Alberto Burgos Aceves, Rosalba Putti and Lillà Lionetti
Nutrients 2018, 10(3), 350; https://doi.org/10.3390/nu10030350 - 14 Mar 2018
Cited by 153 | Viewed by 18043
Abstract
Mitochondrial dysfunction and endoplasmic reticulum (ER) stress have been suggested to play a key role in insulin resistance development. Reactive oxygen species (ROS) production and lipid accumulation due to mitochondrial dysfunction seemed to be important mechanisms leading to cellular insulin resistance. Moreover, mitochondria [...] Read more.
Mitochondrial dysfunction and endoplasmic reticulum (ER) stress have been suggested to play a key role in insulin resistance development. Reactive oxygen species (ROS) production and lipid accumulation due to mitochondrial dysfunction seemed to be important mechanisms leading to cellular insulin resistance. Moreover, mitochondria are functionally and structurally linked to ER, which undergoes stress in conditions of chronic overnutrition, activating the unfolded protein response, which in turn activates the principal inflammatory pathways that impair insulin action. Among the nutrients, dietary fats are believed to play key roles in insulin resistance onset. However, not all dietary fats exert the same effects on cellular energy metabolism. Dietary omega 3 polyunsaturated fatty acids (PUFA) have been suggested to counteract insulin resistance development by modulating mitochondrial bioenergetics and ER stress. In the current review, we summarized current knowledge on the role played by mitochondrial and ER stress in inflammation and insulin resistance onset, focusing on the modulation role of omega 3 PUFA on these stress pathways. Understanding the mechanisms by which omega 3 PUFA modulates cellular metabolism and insulin resistance in peripheral tissues may provide additional details on the potential impact of omega 3 PUFA on metabolic function and the management of insulin resistance in humans. Full article
(This article belongs to the Special Issue Nutrients, Bioactives and Insulin Resistance)
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893 KiB  
Review
Dietary Anthocyanins and Insulin Resistance: When Food Becomes a Medicine
by Tarun Belwal, Seyed Fazel Nabavi, Seyed Mohammad Nabavi and Solomon Habtemariam
Nutrients 2017, 9(10), 1111; https://doi.org/10.3390/nu9101111 - 12 Oct 2017
Cited by 131 | Viewed by 16093
Abstract
Insulin resistance is an abnormal physiological state that occurs when insulin from pancreatic β-cells is unable to trigger a signal transduction pathway in target organs such as the liver, muscles and adipose tissues. The loss of insulin sensitivity is generally associated with persistent [...] Read more.
Insulin resistance is an abnormal physiological state that occurs when insulin from pancreatic β-cells is unable to trigger a signal transduction pathway in target organs such as the liver, muscles and adipose tissues. The loss of insulin sensitivity is generally associated with persistent hyperglycemia (diabetes), hyperinsulinemia, fatty acids and/or lipid dysregulation which are often prevalent under obesity conditions. Hence, insulin sensitizers are one class of drugs currently employed to treat diabetes and associated metabolic disorders. A number of natural products that act through multiple mechanisms have also been identified to enhance insulin sensitivity in target organs. One group of such compounds that gained interest in recent years are the dietary anthocyanins. Data from their in vitro, in vivo and clinical studies are scrutinized in this communication to show their potential health benefit through ameliorating insulin resistance. Specific mechanism of action ranging from targeting specific signal transduction receptors/enzymes to the general antioxidant and anti-inflammatory mechanisms of insulin resistance are presented. Full article
(This article belongs to the Special Issue Nutrients, Bioactives and Insulin Resistance)
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