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JOURNAL ARTICLE
Shannon Rose, Reid D Landes, Kanan K Vyas, Leanna Delhey, Sarah Blossom
BACKGROUND: Obesity-associated inflammation drives the development of insulin resistance and type 2 diabetes. We sought to identify associations of circulating regulatory T cells (Treg) with the degree of obesity (eg, body mass index Z -score [BMIz]), insulin resistance (homeostatic model of insulin resistance [HOMA-IR]), and glycemic control (HbA1c) in children and adolescents. We further sought to examine associations among bioenergetics of peripheral blood mononuclear cells (PBMCs) and CD4 T cells and BMIz, HOMA-IR, and HbA1c...
April 2024: Immunometabolism (Cobham)
#2
JOURNAL ARTICLE
Barbara Becattini, Angela Molinaro, Marcus Henricsson, Jan Borén, Giovanni Solinas
Insulin-PI3K signaling controls insulin secretion. Understanding this feedback mechanism is crucial for comprehending how insulin functions. However, the role of adipocyte insulin-PI3K signaling in controlling insulin secretion in vivo remains unclear. Using adipocyte-specific PI3Kα knockout mice (PI3KαAdQ ) and a panel of isoform-selective PI3K inhibitors, we show that PI3Kα and PI3Kβ activities are functionally redundant in adipocyte insulin signaling. PI3Kβ-selective inhibitors have no effect on adipocyte AKT phosphorylation in control mice but blunt it in adipocytes of PI3KαAdQ mice, demonstrating adipocyte-selective pharmacological PI3K inhibition in the latter...
April 23, 2024: Cell Reports
#3
JOURNAL ARTICLE
Nazan Akdağ, Engin Atli, Drenushe Zhuri, Hazal Sezgi Ner Güler, Yıldız Gürsel Ürün
BACKGROUND: Acne vulgaris (AV) is an inflammatory skin disease caused by the mechanistic target of rapamycin complex 1 (mTORC1). forkhead box protein (Fox) O1 is known to regulate the relationship between the mTORC1 signaling pathway and insulin resistance (IR). Increased mTORC1 signaling is known to predispose one to diseases such as insulin resistance (IR), obesity, and diabetes mellitus. One of the major components of mTORC1 is mTOR. FoxO1 and mTOR play key roles in the onset and progression of metabolic syndrome (MetS)...
March 2024: Curēus
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JOURNAL ARTICLE
Xuelian Dong, Qiang Chen, Wenyan Chi, Zhidong Qiu, Ye Qiu
(1) Background: Diabetes is a common metabolic disease that seriously endangers human health. In the present study, we investigated the therapeutic effects of the active ingredient Eleutheroside B (EB) from the traditional Chinese medicine Eleutheroside on diabetes mellitus in a zebrafish model. Concomitant hepatic injury was also analysed, along with the study of possible molecular mechanisms using metabolomics technology. This work should provide some theoretical references for future experimental studies...
March 29, 2024: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
#5
REVIEW
Antonio Paoli, Grant M Tinsley, Mark P Mattson, Immaculata De Vivo, Ravi Dhawan, Tatiana Moro
Intermittent short-term fasting (ISTF) and ketogenic diets (KDs) exert overlapping but not identical effects on cell metabolism, function, and resilience. Whereas health benefits of KD are largely mediated by the ketone bodies (KBs), ISTF engages additional adaptive physiological responses. KDs act mainly through inhibition of histone deacetylases (HDACs), reduction of oxidative stress, improvement of mitochondria efficiency, and control of inflammation. Mechanisms of action of ISTF include stimulation of autophagy, increased insulin and leptin sensitivity, activation of AMP-activated protein kinase (AMPK), inhibition of the mechanistic target of rapamycin (mTOR) pathway, bolstering mitochondrial resilience, and suppression of oxidative stress and inflammation...
February 2024: Trends in Endocrinology and Metabolism: TEM
#6
JOURNAL ARTICLE
Ryan J Duchatel, Evangeline R Jackson, Sarah G Parackal, Dylan Kiltschewskij, Izac J Findlay, Abdul Mannan, Dilana E Staudt, Bryce C Thomas, Zacary P Germon, Sandra Laternser, Padraic S Kearney, M Fairuz B Jamaluddin, Alicia M Douglas, Tyrone S Beitaki, Holly P McEwen, Mika L Persson, Emily A Hocke, Vaibhav Jain, Michael Aksu, Elizabeth E Manning, Heather C Murray, Nicole M Verrills, Claire Xin Sun, Paul Daniel, Ricardo E Vilain, David A Skerrett-Byrne, Brett Nixon, Susan Hua, Charles E de Bock, Yolanda Colino-Sanguino, Fatima Valdes-Mora, Maria Tsoli, David S Ziegler, Murray J Cairns, Eric H Raabe, Nicholas A Vitanza, Esther Hulleman, Timothy N Phoenix, Carl Koschmann, Frank Alvaro, Christopher V Dayas, Christopher L Tinkle, Helen Wheeler, James R Whittle, David D Eisenstat, Ron Firestein, Sabine Mueller, Santosh Valvi, Jordan R Hansford, David M Ashley, Simon G Gregory, Lindsay B Kilburn, Javad Nazarian, Jason E Cain, Matthew D Dun
Diffuse midline glioma (DMG), including tumors diagnosed in the brainstem (diffuse intrinsic pontine glioma - DIPG), are uniformly fatal brain tumors that lack effective treatment. Analysis of CRISPR-Cas9 loss-of-function gene deletion screens identified PIK3CA and MTOR as targetable molecular dependencies across DIPG patient models, highlighting the therapeutic potential of the blood-brain barrier penetrant PI3K/Akt/mTOR inhibitor, paxalisib. At the human equivalent maximum tolerated dose, mice treated with paxalisib experienced systemic glucose feedback and increased insulin levels commensurate with patients using PI3K inhibitors...
February 6, 2024: Journal of Clinical Investigation
#7
REVIEW
Syed Sayeed Ahmad, Hee Jin Chun, Khurshid Ahmad, Inho Choi
Skeletal muscle (SM) is the largest organ of the body and is largely responsible for the metabolism required to maintain body functions. Furthermore, the maintenance of SM is dependent on the activation of muscle satellite (stem) cells (MSCs) and the subsequent proliferation and fusion of differentiating myoblasts into mature myofibers (myogenesis). Natural compounds are being used as therapeutic options to promote SM regeneration during aging, muscle atrophy, sarcopenia, cachexia, or obesity. In particular, ginseng-derived compounds have been utilized in these contexts, though ginsenoside Rg1 is mostly used for SM mass management...
January 2024: Journal of Ginseng Research
#8
JOURNAL ARTICLE
Hossein Pirani, Afsaneh Soltany, Maryam Hossein Rezaei, Adeleh Khodabakhshi Fard, Rohollah Nikooei, Kimya Khoramipoor, Karim Chamari, Kayvan Khoramipour
Impaired autophagy is a hallmark of diabetes. The current study proposed to investigate if high intensity interval training (HIIT) induced lactate accumulation could stimulate autophagy in type 2 diabetic male rats. 28 male Wistar rats were randomly assigned into four groups: Healthy Control (CO), Diabetes Control (T2D), Exercise (EX), and Diabetes + Exercise (T2D + EX). Diabetes was induced by feeding high-fat diet and administrating single dose of streptozotocin (35 mg/kg). After becoming diabetic, the animals in the exercise groups (EX and T2D + EX) performed an eight-week HIIT (4-10 interval, 80-100% Vmax, 5 days per week)...
January 11, 2024: Scientific Reports
#9
JOURNAL ARTICLE
Hend Al-Jaber, Shamma Al-Muraikhy, Aldana Jabr Jabr, Aisha Yousuf, Najeha Anwardeen, Mohamed Elrayess, Layla Al-Mansoori
UNLABELLED: Cell culture plays a crucial role in addressing fundamental research questions, particularly in studying insulin resistance (IR) mechanisms. Multiple in vitro models are utilized for this purpose, but their technical distinctions and relevance to in vivo conditions remain unclear. This study aims to assess the effectiveness of existing in vitro models in inducing IR and their ability to replicate in vivo IR conditions. BACKGROUND: Insulin resistance (IR) is a cellular condition linked to metabolic disorders...
January 9, 2024: Current Diabetes Reviews
#10
JOURNAL ARTICLE
Valeria Melissa García-Cruz, Clorinda Arias
Metabolic diseases derived from an unhealthy lifestyle have been linked with an increased risk for developing cognitive impairment and even Alzheimer's disease (AD). Although high consumption of saturated fatty acids such as palmitic acid (PA) has been associated with the development of obesity and type II diabetes, the mechanisms connecting elevated neuronal PA levels and increased AD marker expression remain unclear. Among other effects, PA induces insulin resistance, increases intracellular calcium and reactive oxygen species (ROS) production, and reduces the NAD+/NADH ratio, resulting in decreased activity of the deacetylase Sirtuin1 (SIRT1) in neurons...
January 3, 2024: Molecular Neurobiology
#11
REVIEW
Jiahui Gong, Xilong Gao, Shaoyang Ge, Hongliang Li, Ran Wang, Liang Zhao
The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) is a crucial innate defence mechanism against viral infection in the innate immune system, as it principally induces the production of type I interferons. Immune responses and metabolic control are inextricably linked, and chronic low-grade inflammation promotes the development of metabolic diseases. The cGAS-STING pathway activated by double-stranded DNA (dsDNA), cyclic dinucleotides (CDNs), endoplasmic reticulum stress (ER stress), mitochondrial stress, and energy imbalance in metabolic cells and immune cells triggers proinflammatory responses and metabolic disorders...
2024: International Journal of Biological Sciences
#12
JOURNAL ARTICLE
Xiaolin Chen, Zhuoni Xiao, Qing Liu, Deng Luo, Yuli Cai, Mingxia Fan
INTRODUCTION: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have shown neuroprotective effects in obese mice. However, whether SGLT2i can ameliorate high-fat diet (HFD)-related ovulation disorders remains unknown. The aim of this research was to investigate whether dapagliflozin improves HFD-induced ovulatory dysfunction by attenuating microglia-mediated hypothalamic inflammation. METHODS: C57BL/6J female mice fed HFD were treated with dapagliflozin (1mg/kg) for 22 weeks...
December 26, 2023: Neuroendocrinology
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JOURNAL ARTICLE
Qamraa H Alqahtani, Samiyah Alshehri, Ahlam M Alhusaini, Wedad S Sarawi, Sana S Alqarni, Raessa Mohamed, Meha N Kumar, Juman Al-Saab, Iman H Hasan
Diabetes is a ubiquitous disease that causes several complications. It is associated with insulin resistance, which affects the metabolism of proteins, carbohydrates, and fats and triggers liver diseases such as fatty liver disease, steatohepatitis, fibrosis, and cirrhosis. Despite the effectiveness of Sitagliptin (ST) as an antidiabetic drug, its role in diabetes-induced liver injury is yet to be fully investigated. Therefore, this study aims to investigate the effect of ST on hepatic oxidative injury, inflammation, apoptosis, and the mTOR/NF-κB/NLRP3 signaling pathway in streptozotocin (STZ)-induced liver injury...
December 18, 2023: Diseases (Basel)
#14
JOURNAL ARTICLE
Oto Inoue, Chiaki Goten, Daiki Hashimuko, Kosei Yamaguchi, Yusuke Takeda, Ayano Nomura, Hiroshi Ootsuji, Shinichiro Takashima, Kenji Iino, Hirofumi Takemura, Manasi Halurkar, Hee-Woong Lim, Vivian Hwa, Joan Sanchez-Gurmaches, Soichiro Usui, Masayuki Takamura
Therapeutic angiogenesis using mesenchymal stem/stromal cell grafts have shown modest and controversial effects in preventing amputation for patients with critical limb ischemia. Through single-cell transcriptomic analysis of human tissues, we identify CD271+ progenitors specifically from subcutaneous adipose tissue (AT) as having the most prominent pro-angiogenic gene profile distinct from other stem cell populations. AT-CD271+ progenitors demonstrate robust in vivo angiogenic capacity over conventional adipose stromal cell grafts, characterized by long-term engraftment, augmented tissue regeneration, and significant recovery of blood flow in a xenograft model of limb ischemia...
December 19, 2023: Cell reports medicine
#15
JOURNAL ARTICLE
Deyu Li, Yingchao Hu, Xin Liu, Guran Yu
OBJECTIVES: To explore the mechanism of action of Anemarrhenae Rhizoma in treatment of Alzheimer's Disease (AD) through network pharmacology analysis and experimental validation. METHODS: The active ingredients and targets of Anemarrhenae Rhizoma for treatment of AD were screened with network pharmacological methods, the protein-protein interaction (PPI) network was constructed and the core targets were analyzed, enriching Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis was performed...
December 14, 2023: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
#16
JOURNAL ARTICLE
F Blaine Hollinger, Gokul C Das
INTRODUCTION: Chronic HCV infection results in insulin resistance (IR) through interaction of pathways for glucose homeostasis, insulin signaling, and autophagy. Not known is how soon the pathways are activated, and how IR is related to the signals generated by catabolic and anabolic conditions occurring in infected cells. We have extended our studies to a cell culture system mimicking acute infection and to downstream pathways involving energy-sensor AMPK and nutrient-sensor mTOR that are active in catabolic and anabolic processes within the infected cells...
December 15, 2023: Intervirology
#17
JOURNAL ARTICLE
Daewon Han, Deokryong Kim, Haeil Kim, Jeonga Lee, Jungmook Lyu, Jong-Seok Kim, Jongdae Shin, Jeong Sig Kim, Do Kyung Kim, Hwan-Woo Park
Introduction: Metabolism-associated fatty liver disease (MAFLD) is a global health concern because of its association with obesity, insulin resistance, and other metabolic abnormalities. Methylsulfonylmethane (MSM), an organic sulfur compound found in various plants and animals, exerts antioxidant and anti-inflammatory effects. Here, we aimed to assess the anti-obesity activity and autophagy-related mechanisms of Methylsulfonylmethane. Method: Human hepatoma (HepG2) cells treated with palmitic acid (PA) were used to examine the effects of MSM on autophagic clearance...
2023: Frontiers in Pharmacology
#18
JOURNAL ARTICLE
Zhen Yu, Junyong Han, Lisha Li, Qiufeng Zhang, Ayun Chen, Jinyan Chen, Kun Wang, Jingjun Jin, Huangyuan Li, Gang Chen
Triclosan (TCS) is an antimicrobial compound incorporated into more than 2000 consumer products. This compound is frequently detected in the human body and causes ubiquitous contamination in the environment, thereby raising concerns about its impact on human health and environmental pollution. Here, we demonstrated that 20 weeks' exposure of TCS drove the development of glucose intolerance by inducing compositional and functional alterations in intestinal microbiota in rats. Fecal-transplantation experiments corroborated the involvement of gut microbiota in TCS-induced glucose-tolerance impairment...
December 3, 2023: Food and Chemical Toxicology
#19
JOURNAL ARTICLE
Shuting Zhuang, Xian Zhou, Xiaowen Yang, Dennis Chang, Tao Chen, Yibin Sun, Chenxiang Wang, Chutian Zhang, Jichao Jiang, Yong Chen, Xiaohui Lin, Xiaoning Wang, Wenzhen Yu, Xinjun Lin, Caigu He, Yanfang Zheng, Jieping Zhang, Hong Shi
Dendrobium mixture (DM) is a patented Chinese herbal medicine which has been shown to ameliorate type 2 diabetes mellitus (T2DM) with non-alcoholic fatty liver disease (NAFLD) in vivo and in vitro . We aimed to investigate the underlying mechanism of DM as a therapeutic agent in attenuating liver steatosis in relation to type 2 diabetes mellitus (T2DM). DM (16.2 g/kg/d) was administered to db / db mice for 4 weeks. The db/m mice and db/db mice in the control and model groups were given normal saline. Additionally, DM (11...
November 2023: Heliyon
#20
JOURNAL ARTICLE
Alex J T Yang, Ahmad Mohammad, Michael S Finch, Evangelia Tsiani, Gaynor Spencer, Aleksandar Necakov, Rebecca E K MacPherson
Insulin resistance (IR) is associated with reductions in neuronal proteins often observed with Alzheimer's disease (AD), however, the mechanisms through which IR promotes neurodegeneration/AD pathogenesis are poorly understood. Metformin (MET), a potent activator of the metabolic regulator AMPK is used to treat IR but its effectiveness for AD is unclear. We have previously shown that chronic AMPK activation impairs neurite growth and protein synthesis in SH-SY5Y neurons, however, AMPK activation in IR was not explored...
November 2023: Physiological Reports
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