Review
Nutrition & Dietetics
Jing Xu, Fei Mao
Summary: NAFLD is the most common chronic liver disease worldwide with the rising incidence of obesity and diabetes. A long-term high-salt diet has been suggested to independently increase the risk of NAFLD. Lifestyle intervention remains an effective approach for NAFLD treatment due to lack of therapeutic medication. Many studies have been reported regarding the mechanism of high-salt diet-induced NAFLD.
EUROPEAN JOURNAL OF CLINICAL NUTRITION
(2022)
Article
Immunology
Vitor R. Munoz, Rafael C. Gaspar, Matheus B. Severino, Ana P. A. Macedo, Fernando M. Simabuco, Eduardo R. Ropelle, Dennys E. Cintra, Adelino S. R. da Silva, Young-Bum Kim, Jose Rodrigo Pauli
Summary: Physical exercise can restore the levels of RhoA and ROCK2 proteins in the skeletal muscle of obese animals, increase phosphorylation of IRS1 and Akt proteins, and decrease levels of inhibitory regulators such as PTEN and PTP-1B. These findings suggest that exercise-induced upregulation of the RhoA-ROCK2 signaling pathway in skeletal muscle is associated with improved systemic insulin sensitivity in obese mice.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Mohammad Shamsul Ola
Summary: Obesity has become a serious health problem worldwide, leading to various health complications. This study investigated the molecular mechanism of insulin resistance in the skeletal muscle of obese Zucker rats and found altered insulin receptor signal transduction. These findings contribute to our understanding of obesity and type 2 diabetes in humans.
CURRENT ISSUES IN MOLECULAR BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Mary Priyanka Udumula, Sureshbabu Mangali, Jaspreet Kalra, Deepika Dasari, Srashti Goyal, Vandana Krishna, Srivarsha Reddy Bollareddy, Dharamrajan Sriram, Arti Dhar, Audesh Bhat
Summary: Metabolic disorders in young population are increasing due to dietary habits and lack of physical activity. The study investigated the role of PKR pathway in diabetes induced by high fructose and streptozotocin, and found that PKR inhibitor could attenuate the impairments caused by high fructose and streptozotocin. Inhibition of PKR can protect insulin sensitive organs and tissues from diabetic impairments induced by high fructose.
SCIENTIFIC REPORTS
(2021)
Article
Microbiology
Axel Dietschmann, Sebastian Schruefer, Stefanie Westermann, Fiona Henkel, Kirstin Castiglione, Ralf Willebrand, Jasmin Adam, Jurgen Ruland, Roland Lang, Donald C. Sheppard, Julia Esser-von-Bieren, Daniel Radtke, Sven Krappmann, David Voehringer
Summary: Eosinophilia is associated with various inflammatory diseases, such as allergic bronchopulmonary aspergillosis (ABPA). It has been shown that direct interaction between eosinophils and Aspergillus fumigatus is essential for the activation of eosinophils, which then secrete multiple proinflammatory mediators. The PI3K-AKT-mTOR pathway plays a crucial role in A. fumigatus-induced eosinophil activation.
Review
Pharmacology & Pharmacy
Yue Tong, Sai Xu, Lili Huang, Chen Chen
Summary: The prevalence of obesity is a major cause of chronic metabolic disorders. This review discusses the mechanisms of insulin resistance and current therapeutic strategies for obesity.
DRUG DISCOVERY TODAY
(2022)
Article
Biology
Amanda E. Brandon, Lewin Small, Tuong-Vi Nguyen, Eurwin Suryana, Henry Gong, Christian Yassmin, Sarah E. Hancock, Tamara Pulpitel, Sophie Stonehouse, Letisha Prescott, Melkam A. Kebede, Belinda Yau, Lake-Ee Quek, Greg M. Kowalski, Clinton R. Bruce, Nigel Turner, Gregory J. Cooney
Summary: Obesity is generally associated with insulin resistance and increased risk of developing type 2 diabetes, but there is a subset of obese individuals who remain insulin sensitive. Recent research suggests that high carbohydrate diets can cause obesity in mice without glucose intolerance. This study found that dietary manipulation can influence insulin action independently of adiposity, and specific ceramide species may be associated with these differences.
Review
Pharmacology & Pharmacy
Jingqian Su, Lu Tang, Yingsheng Luo, Jingran Xu, Songying Ouyang
Summary: This article provides a comprehensive analysis of the structure and function of INSR and IRS proteins, as well as the drugs used for the treatment of diabetes. It serves as a valuable reference for the advancement of novel therapeutic agents for diabetes management.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Endocrinology & Metabolism
Jose E. Galgani, Rodrigo Fernandez-Verdejo
Summary: Glucose, fatty acids, and amino acids are oxidized to produce ATP for energy, and the complex adaptive systems in the body adjust fuel oxidation rates based on fuel availability. Metabolic flexibility refers to the ability of cells, tissues, or organisms to adapt fuel oxidation to fuel availability, which can be impaired in conditions like insulin resistance, diabetes, and obesity. Mitochondrial dysfunction in these conditions has been linked to metabolic inflexibility and overall metabolic health.
Article
Oncology
Evan K. Noch, Laura N. Palma, Isaiah Yim, Nayah Bullen, Yuqing Qiu, Hiranmayi Ravichandran, Junbum Kim, Andre Rendeiro, Melissa B. Davis, Olivier Elemento, David J. Pisapia, Kevin Zhai, Hongbiao Carl LeKaye, Jason A. Koutcher, Patrick Y. Wen, Keith L. Ligon, Lewis C. Cantley
Summary: This study investigated the critical role of insulin feedback in the poor clinical efficacy of phosphatidylinositol 3-kinase (PI3K) inhibition in cancer and the independent association between hyperglycemia and poor prognosis in glioblastoma (GBM). It was found that combining anti-hyperglycemic therapy with PI3K inhibition improved treatment efficacy in a GBM mouse model. Analysis of clinical trial data revealed that hyperglycemia was independently associated with poor progression-free survival in GBM patients.
Article
Multidisciplinary Sciences
Ritwik Datta, Carlos O. Lizama, Amin K. Soltani, William Mckleroy, Michael J. Podolsky, Christopher D. Yang, Tony L. Huynh, Kelly M. Cautivo, Biao Wang, Suneil K. Koliwad, Nada A. Abumrad, Kamran Atabai
Summary: The role of MFGE8 in regulating insulin sensitivity through the ?v05 integrin pathway is explored in this study. Blocking the MFGE8/05 pathway enhances insulin-stimulated glucose uptake, whereas augmentation dampens it. Additionally, insulin-induced surface enrichment of MFGE8 in skeletal muscle dampens insulin receptor signaling, establishing a potential pathway for improving insulin sensitivity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Endocrinology & Metabolism
Vicente Herrero-Aguayo, Juan M. Jimenez-Vacas, Prudencio Saez-Martinez, Enrique Gomez-Gomez, Juan L. Lopez-Canovas, Lourdes Garrido-Sanchez, Aura D. Herrera-Martinez, Laura Garcia-Bermejo, Manuel Macias-Gonzalez, Jose Lopez-Miranda, Justo P. Castano, Manuel D. Gahete, Raul M. Luque
Summary: The study revealed that miR-4454 levels were higher in plasma of obese individuals and associated with insulin resistance, highlighting its potential as a target for obesity-related interventions. miR-4454 was found to be highly expressed in prostate and liver tissues, regulated by insulin, and may impair cellular response to insulin, particularly in prostate gland, through modulation of the splicing process.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2021)
Article
Biochemistry & Molecular Biology
Sasja Blokzijl-Franke, Bas Ponsioen, Stefan Schulte-Merker, Philippe Herbomel, Karima Kissa, Suma Choorapoikayil, Jeroen den Hertog
Summary: The study found that HSPCs in mutant zebrafish embryos lacking pten function exhibited death during development, which could be rescued by inhibiting PI3K, while inhibiting PI3K in wild-type embryos also induced HSPC death. PI3K signaling tightly controls HSPC survival, with both up- and downregulation of the signaling pathway reducing stemness of HSPCs.
Article
Biochemistry & Molecular Biology
Biqin Zhang, Cheukyau Luk, Joyce Valadares, Christos Aronis, Lazaros C. Foukas
Summary: The study found that p110α plays a key role in the activation downstream of both the insulin receptor and the beta-adrenergic receptor, with its interaction with Ras enhancing its activation strength by insulin. This offers further insights into the role of PI3K isoforms in energy metabolism regulation and potential therapeutic applications.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Mohamed E. Shaker, Hesham A. M. Gomaa, Sara H. Hazem, Mohamed A. Abdelgawad, Mohamed El-Mesery, Ahmed A. Shaaban
Summary: The study investigated the role of PI3K alpha in hepatic sterile inflammation caused by APAP-overdose and found that the selective modulation of PI3K alpha activity by alpelisib can inhibit the inflammatory response and immune cell infiltration. Alpelisib reduced the escalation of liver function biomarkers and hepatic necroinflammation score, as well as apoptosis and proliferation in liver hepatocytes induced by APAP. It also limited the overproduction of pro-inflammatory cytokines and the activation of several signal transduction proteins.
FRONTIERS IN PHARMACOLOGY
(2023)