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Advances in Insulin Resistance

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: 15 April 2024 | Viewed by 17207

Special Issue Editors

Department of Food Science and Nutrition, University of Ulsan, Ulsan 44610, Republic of Korea
Interests: transcription; nuclear receptors; coregulators; cancer; metabolism; glycolysis
Special Issues, Collections and Topics in MDPI journals
Department of Food Science and Nutrition, Pusan National University, Busan 46241, Republic of Korea
Interests: bioactive compounds; polyphenols; metabolites; bioavailability; gut microbiota; inflammation; inflammatory bowel disease; obesity; chronic disease
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Insulin resistance arises when cells in fat, skeletal muscle, the heart and the liver cannot respond to insulin hormone. It has been reported that insulin resistance plays a critical risk factor for development of type 2 diabetes mellitus, cardiovascular disease and other related metabolic diseases. Development of insulin resistance is strongly associated with several important metabolic pathways such as glucose/lipid metabolism, ectopic lipid accumulation, mitochondria dysfunction, ER stress and inflammation. The aim of this Special Issues is to find and delineate new molecular targets and mechanisms which reduces a main cause of insulin resistance.

Dr. ByungYong Ahn
Dr. HyeMee Kim
Guest Editors

Manuscript Submission Information

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Keywords

  • insulin resistance
  • obesity
  • metabolic diseases
  • diabetes
  • metabolism
  • inflammation

Published Papers (6 papers)

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Research

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31 pages, 2034 KiB  
Article
Ketosis Suppression and Ageing (KetoSAge): The Effects of Suppressing Ketosis in Long Term Keto-Adapted Non-Athletic Females
by Isabella D. Cooper, Yvoni Kyriakidou, Kurtis Edwards, Lucy Petagine, Thomas N. Seyfried, Tomas Duraj, Adrian Soto-Mota, Andrew Scarborough, Sandra L. Jacome, Kenneth Brookler, Valentina Borgognoni, Vanusa Novaes, Rima Al-Faour and Bradley T. Elliott
Int. J. Mol. Sci. 2023, 24(21), 15621; https://doi.org/10.3390/ijms242115621 - 26 Oct 2023
Cited by 1 | Viewed by 9794
Abstract
Most studies on ketosis have focused on short-term effects, male athletes, or weight loss. Hereby, we studied the effects of short-term ketosis suppression in healthy women on long-standing ketosis. Ten lean (BMI 20.5 ± 1.4), metabolically healthy, pre-menopausal women (age 32.3 ± 8.9) [...] Read more.
Most studies on ketosis have focused on short-term effects, male athletes, or weight loss. Hereby, we studied the effects of short-term ketosis suppression in healthy women on long-standing ketosis. Ten lean (BMI 20.5 ± 1.4), metabolically healthy, pre-menopausal women (age 32.3 ± 8.9) maintaining nutritional ketosis (NK) for > 1 year (3.9 years ± 2.3) underwent three 21-day phases: nutritional ketosis (NK; P1), suppressed ketosis (SuK; P2), and returned to NK (P3). Adherence to each phase was confirmed with daily capillary D-beta-hydroxybutyrate (BHB) tests (P1 = 1.9 ± 0.7; P2 = 0.1 ± 0.1; and P3 = 1.9 ± 0.6 pmol/L). Ageing biomarkers and anthropometrics were evaluated at the end of each phase. Ketosis suppression significantly increased: insulin, 1.78-fold from 33.60 (± 8.63) to 59.80 (± 14.69) pmol/L (p = 0.0002); IGF1, 1.83-fold from 149.30 (± 32.96) to 273.40 (± 85.66) µg/L (p = 0.0045); glucose, 1.17-fold from 78.6 (± 9.5) to 92.2 (± 10.6) mg/dL (p = 0.0088); respiratory quotient (RQ), 1.09-fold 0.66 (± 0.05) to 0.72 (± 0.06; p = 0.0427); and PAI-1, 13.34 (± 6.85) to 16.69 (± 6.26) ng/mL (p = 0.0428). VEGF, EGF, and monocyte chemotactic protein also significantly increased, indicating a pro-inflammatory shift. Sustained ketosis showed no adverse health effects, and may mitigate hyperinsulinemia without impairing metabolic flexibility in metabolically healthy women. Full article
(This article belongs to the Special Issue Advances in Insulin Resistance)
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17 pages, 3225 KiB  
Article
The Attenuation of Insulin/IGF-1 Signaling Pathway Plays a Crucial Role in the Myo-Inositol-Alleviated Aging in Caenorhabditis elegans
by Nae-Cherng Yang, Chia-Yu Chin, Ya-Xin Zheng and Inn Lee
Int. J. Mol. Sci. 2023, 24(7), 6194; https://doi.org/10.3390/ijms24076194 - 24 Mar 2023
Cited by 2 | Viewed by 1258
Abstract
Myo-Inositol (MI) has been shown to alleviate aging in Caenorhabditis (C). elegans. However, the mechanism by which MI alleviates aging remains unclear. In this study, we investigate whether MI can modulate the PI3K so as to attenuate the insulin/IGF-1 signaling (IIS) pathway and [...] Read more.
Myo-Inositol (MI) has been shown to alleviate aging in Caenorhabditis (C). elegans. However, the mechanism by which MI alleviates aging remains unclear. In this study, we investigate whether MI can modulate the PI3K so as to attenuate the insulin/IGF-1 signaling (IIS) pathway and exert the longevity effect. The wild-type C. elegans and two mutants of AKT-1 and DAF-16 were used to explore the mechanism of MI so as to extend the lifespan, as well as to improve the health indexes of pharyngeal pumping and body bend, and an aging marker of autofluorescence in the C. elegans. We confirmed that MI could significantly extend the lifespan of C. elegans. MI also ameliorated the pharyngeal pumping and body bend and decreased autofluorescence. We further adopted the approach to reveal the loss-of-function mutants to find the signaling mechanism of MI. The functions of the lifespan-extending, health-improving, and autofluorescence-decreasing effects of MI disappeared in the AKT-1 and DAF-16 mutants. MI could also induce the nuclear localization of the DAF-16. Importantly, we found that MI could dramatically inhibit the phosphoinositide 3-kinase (PI3K) activity in a dose-dependent manner with an IC50 of 90.2 μM for the p110α isoform of the PI3K and 21.7 μM for the p110β. In addition, the downregulation of the PI3K expression and the inhibition of the AKT phosphorylation by MI was also obtained. All these results demonstrate that MI can inhibit the PI3K activity and downregulate the PI3K expression, and the attenuation of the IIS pathway plays a crucial role for MI in alleviating aging in C. elegans. Full article
(This article belongs to the Special Issue Advances in Insulin Resistance)
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17 pages, 1738 KiB  
Article
Sex-Specific Models to Predict Insulin Secretion and Sensitivity in Subjects with Overweight and Obesity
by Myriam Beaudry, Simon Bissonnette, Valérie Lamantia, Marie Devaux and May Faraj
Int. J. Mol. Sci. 2023, 24(7), 6130; https://doi.org/10.3390/ijms24076130 - 24 Mar 2023
Viewed by 1173
Abstract
Sex-specific differences exist in insulin secretion (ISec) and sensitivity (IS) in humans. However, current fasting indices used to estimate them, such as HOMA and QUICKI, are not sex-specific. We aimed to develop sex-specific models to improve the prediction of ISec and IS by [...] Read more.
Sex-specific differences exist in insulin secretion (ISec) and sensitivity (IS) in humans. However, current fasting indices used to estimate them, such as HOMA and QUICKI, are not sex-specific. We aimed to develop sex-specific models to improve the prediction of ISec and IS by fasting measures in adults with overweight/obesity. A post hoc analysis was conducted on baseline data of two clinical trials completed between 2010 and 2020 (37 men and 61 postmenopausal women, 45–73 years, BMI > 25 kg/m2, without chronic disease). Glucose-induced insulin or C-peptide secretions and IS were measured using gold-standard Botnia-clamps, which is a 1 h intravenous glucose tolerance test followed by a 3 h hyperinsulinemic–euglycemic clamp. Stepwise regression analysis using anthropometric and fasting plasma glucose, insulin, and lipoprotein-related measures was used to predict ISec and IS. First-phase, second-phase and total glucose-induced ISec were predicted by a combination of fasting plasma insulin and apoB without or with plasma glucose, triglyceride, and waist circumference in women (R2 = 0.58–0.69), and by plasma insulin and glucose without or with BMI and cholesterol in men (R2 = 0.41–0.83). Plasma C-peptide, alone in men or followed by glucose in women, predicted C-peptide secretion. IS was predicted by plasma insulin and waist circumference, followed by HDL-C in women (R2 = 0.57) or by glucose in men (R2 = 0.67). The sex-specific models agreed with the Botnia-clamp measurements of ISec and IS more than with HOMA or QUICKI. Sex-specific models incorporating anthropometric and lipoprotein-related parameters allowed better prediction of ISec and IS in subjects with overweight or obesity than current indices that rely on glucose and insulin alone. Full article
(This article belongs to the Special Issue Advances in Insulin Resistance)
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Review

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34 pages, 1049 KiB  
Review
Glucagon and Its Receptors in the Mammalian Heart
by Joachim Neumann, Britt Hofmann, Stefan Dhein and Ulrich Gergs
Int. J. Mol. Sci. 2023, 24(16), 12829; https://doi.org/10.3390/ijms241612829 - 15 Aug 2023
Cited by 1 | Viewed by 1270
Abstract
Glucagon exerts effects on the mammalian heart. These effects include alterations in the force of contraction, beating rate, and changes in the cardiac conduction system axis. The cardiac effects of glucagon vary according to species, region, age, and concomitant disease. Depending on the [...] Read more.
Glucagon exerts effects on the mammalian heart. These effects include alterations in the force of contraction, beating rate, and changes in the cardiac conduction system axis. The cardiac effects of glucagon vary according to species, region, age, and concomitant disease. Depending on the species and region studied, the contractile effects of glucagon can be robust, modest, or even absent. Glucagon is detected in the mammalian heart and might act with an autocrine or paracrine effect on the cardiac glucagon receptors. The glucagon levels in the blood and glucagon receptor levels in the heart can change with disease or simultaneous drug application. Glucagon might signal via the glucagon receptors but, albeit less potently, glucagon might also signal via glucagon-like-peptide-1-receptors (GLP1-receptors). Glucagon receptors signal in a species- and region-dependent fashion. Small molecules or antibodies act as antagonists to glucagon receptors, which may become an additional treatment option for diabetes mellitus. Hence, a novel review of the role of glucagon and the glucagon receptors in the mammalian heart, with an eye on the mouse and human heart, appears relevant. Mouse hearts are addressed here because they can be easily genetically modified to generate mice that may serve as models for better studying the human glucagon receptor. Full article
(This article belongs to the Special Issue Advances in Insulin Resistance)
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14 pages, 997 KiB  
Review
The Role of Macrophage Populations in Skeletal Muscle Insulin Sensitivity: Current Understanding and Implications
by Min-Kyeong Lee, Heeyeon Ryu, Ji Yun Van, Myeong-Jin Kim, Hyeon Hak Jeong, Won-Kyo Jung, Joo Yun Jun and Bonggi Lee
Int. J. Mol. Sci. 2023, 24(14), 11467; https://doi.org/10.3390/ijms241411467 - 14 Jul 2023
Cited by 1 | Viewed by 1197
Abstract
Insulin resistance is a crucial factor in the development of type 2 diabetes mellitus (T2DM) and other metabolic disorders. Skeletal muscle, the body’s largest insulin-responsive tissue, plays a significant role in the pathogenesis of T2DM due to defects in insulin signaling. Recently, there [...] Read more.
Insulin resistance is a crucial factor in the development of type 2 diabetes mellitus (T2DM) and other metabolic disorders. Skeletal muscle, the body’s largest insulin-responsive tissue, plays a significant role in the pathogenesis of T2DM due to defects in insulin signaling. Recently, there has been growing evidence that macrophages, immune cells essential for tissue homeostasis and injury response, also contribute to the development of skeletal muscle insulin resistance. This review aims to summarize the current understanding of the role of macrophages in skeletal muscle insulin resistance. Firstly, it provides an overview of the different macrophage populations present in skeletal muscle and their specific functions in the development of insulin resistance. Secondly, it examines the underlying mechanisms by which macrophages promote or alleviate insulin resistance in skeletal muscle, including inflammation, oxidative stress, and altered metabolism. Lastly, the review discusses potential therapeutic strategies targeting macrophages to improve skeletal muscle insulin sensitivity and metabolic health. Full article
(This article belongs to the Special Issue Advances in Insulin Resistance)
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17 pages, 2333 KiB  
Review
The Function of MondoA and ChREBP Nutrient—Sensing Factors in Metabolic Disease
by Byungyong Ahn
Int. J. Mol. Sci. 2023, 24(10), 8811; https://doi.org/10.3390/ijms24108811 - 16 May 2023
Cited by 3 | Viewed by 1703
Abstract
Obesity is a major global public health concern associated with an increased risk of many health problems, including type 2 diabetes, heart disease, stroke, and some types of cancer. Obesity is also a critical factor in the development of insulin resistance and type [...] Read more.
Obesity is a major global public health concern associated with an increased risk of many health problems, including type 2 diabetes, heart disease, stroke, and some types of cancer. Obesity is also a critical factor in the development of insulin resistance and type 2 diabetes. Insulin resistance is associated with metabolic inflexibility, which interferes with the body’s ability to switch from free fatty acids to carbohydrate substrates, as well as with the ectopic accumulation of triglycerides in non-adipose tissue, such as that of skeletal muscle, the liver, heart, and pancreas. Recent studies have demonstrated that MondoA (MLX-interacting protein or MLXIP) and the carbohydrate response element-binding protein (ChREBP, also known as MLXIPL and MondoB) play crucial roles in the regulation of nutrient metabolism and energy homeostasis in the body. This review summarizes recent advances in elucidating the function of MondoA and ChREBP in insulin resistance and related pathological conditions. This review provides an overview of the mechanisms by which MondoA and ChREBP transcription factors regulate glucose and lipid metabolism in metabolically active organs. Understanding the underlying mechanism of MondoA and ChREBP in insulin resistance and obesity can foster the development of new therapeutic strategies for treating metabolic diseases. Full article
(This article belongs to the Special Issue Advances in Insulin Resistance)
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