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15 pages, 2819 KiB

Open AccessArticle

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 107 | Viewed by 10187

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

Open AccessArticle

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 41 | Viewed by 5680

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

Open AccessArticle

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 28 | Viewed by 6137

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), Kir_6.2, and Cav_1.2 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

Open AccessReview

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 101 | Viewed by 18540

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

Open AccessReview

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 80 | Viewed by 9564

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

Open AccessReview

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 25 | Viewed by 10755

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

Open AccessReview

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 50 | Viewed by 9135

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

Open AccessReview

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 135 | Viewed by 16186

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

Open AccessReview

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 121 | Viewed by 14735

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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