Article
Endocrinology & Metabolism
Pablo Panico, Myrian Velasco, Ana Maria Salazar, Patricia Ostrosky-Wegman, Marcia Hiriart
Summary: This study evaluated the effects of sucrose and arsenic exposure on the pathways involved in insulin-stimulated GLUT4 translocation in muscle. The results showed that sucrose and arsenic exposure induced systemic insulin resistance, with defects in GLUT4 retention and docking in the quadriceps muscle, and impacts on the Akt pathway and proteolytic pathway in the gastrocnemius muscle.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Multidisciplinary Sciences
Lisbeth L. V. Moller, Mona S. Ali, Jonathan Davey, Steffen H. Raun, Nicoline R. Andersen, Jonathan Z. Long, Hongwei Qian, Jacob F. Jeppesen, Carlos Henriquez- Olguin, Emma Frank, Thomas E. Jensen, Kurt Hojlund, Jorgen F. P. Wojtaszewski, Joachim Nielsen, Tim T. Chiu, Mark P. Jedrychowski, Paul Gregorevic, Amira Klip, Erik A. Richter, Lykke Sylow
Summary: RhoGDIα is identified as a key regulator in controlling skeletal muscle insulin sensitivity by interacting with Rac1 and modulating GLUT4 translocation. Overexpression of RhoGDIα impairs insulin action and glucose tolerance, and elevated RhoGDIα protein content is observed in skeletal muscles of insulin-resistant patients with type 2 diabetes. This study highlights the clinical relevance of RhoGDIα as a controller of skeletal muscle insulin sensitivity and whole-body glucose homeostasis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Man Piu Chan, Nobuyuki Takenaka, Takaya Satoh
Summary: Insulin-stimulated glucose uptake in skeletal muscle is impaired in Lep(ob/ob) mouse model due to the complete inhibition of Akt2-mediated activation of Rac1 and partial inhibition of RalA activation downstream of Rac1.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Margarita Beckerman, Chava Harel, Inbal Michael, Amira Klip, Philip J. Bilan, Emily J. Gallagher, Derek LeRoith, Eli C. Lewis, Eddy Karnieli, Shulamit Levenberg
Summary: The study successfully demonstrated that engineered muscle constructs composed of GLUT4-overexpressing cells can effectively reduce and stabilize basal glucose levels in diabetic mice, suggesting a potential innovative modality for T2D therapy.
Article
Cell Biology
Rosa Isela Ortiz-Huidobro, Carlos Larque, Myrian Velasco, Juan Pablo Chavez-Maldonado, Jean Sabido, Yuriko Itzel Sanchez-Zamora, Marcia Hiriart
Summary: This study examined the sexual dimorphism and underlying mechanisms of physiological insulin resistance in rats at postnatal day 20 (p20). The results showed that both male and female p20 rats exhibited elevated glucose and insulin levels, reduced systemic insulin sensitivity, and glucose intolerance. Additionally, there were sex- and tissue-related differences in the activation of insulin signaling proteins in p20 rats compared to adult rats.
CELL COMMUNICATION AND SIGNALING
(2022)
Article
Endocrinology & Metabolism
Kohei Kido, Tatsuro Egawa, Shinya Watanabe, Kentaro Kawanaka, Jonas T. Treebak, Tatsuya Hayashi
Summary: This study demonstrated the synergistic enhancement of insulin-stimulated TBC1D4 phosphorylation and glucose uptake by fasting and prior muscle contraction, which is associated with augmented AMPK pathway activation.
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
(2022)
Article
Cell Biology
Zoltan M. Kohler, Gyorgy Trencsenyi, Laszlo Juhasz, Agnes Zvara, Judit P. Szabo, Laszlo Dux, Laszlo G. Puskas, Laszlo Rovo, Aniko Keller-Pinter
Summary: Skeletal muscle plays a crucial role in glucose metabolism. This study demonstrates that tilorone can improve glucose uptake and metabolism by enhancing BMP signaling and Akt2/AS160 signaling pathways in C2C12 myoblasts and differentiated myotubes. The in vivo experiments show that tilorone administration increases glucose uptake in skeletal muscle, liver, and adipose tissue of mice. These findings provide new insights for the treatment of type 2 diabetes.
JOURNAL OF CELLULAR PHYSIOLOGY
(2023)
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
Geriatrics & Gerontology
Ravikumar Manickam, Jared Tur, Sachin L. Badole, Kalyan C. Chapalamadugu, Puja Sinha, Zhiying Wang, David W. Russ, Marco Brotto, Srinivas M. Tipparaju
Summary: This study aimed to investigate the effects of P7C3 on skeletal muscle function in type 2 diabetic mice. The results showed that P7C3 treatment improved diabetes and skeletal muscle function by activating NAMPT.
JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE
(2022)
Article
Biochemistry & Molecular Biology
Aiwen Jiang, Hongyun Guo, Xiaoyu Jiang, Jingli Tao, Wangjun Wu, Honglin Liu
Summary: This study reveals the down-regulation of G6PD during skeletal muscle development and explores its importance in myogenic differentiation. G6PD deficiency may provide a new perspective for the treatment of insulin resistance and type-2 diabetes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, Research & Experimental
Aline Pedro de Melo Yamamoto, Fernando Yamamoto Chiba, Rafael Dias Astolphi, Max Sander de Oliveira da Mota, Mario Jefferson Quirino Louzada, Maria Sara de Lima Coutinho Mattera, Clea Adas Saliba Garbin, Edilson Ervolino, Thais Veronica Saori Tsosura, Bianca Elvira Belardi, Rodrigo Martins dos Santos, Maristela Mitiko Okamoto, Ubiratan Fabres Machado, Doris Hissako Matsushita
Summary: The study demonstrated that resistance training had positive effects on glycemia, GLUT4 content, bone mineral density, and microstructural and biomechanical properties of osteopenic and non-osteopenic diabetic rats. These effects were not observed in the control groups without resistance training.
Article
Biology
Jonas R. Knudsen, Kaspar W. Persson, Carlos Henriquez-Olguin, Zhencheng Li, Nicolas Di Leo, Sofie A. Hesselager, Steffen H. Raun, Janne R. Hingst, Raphael Trouillon, Martin Wohlwend, Jorgen F. P. Wojtaszewski, Martin A. M. Gijs, Thomas Elbenhardt Jensen, Michael Czech
Summary: Microtubules play a crucial role in GLUT4 trafficking and maintaining an insulin-responsive GLUT4 pool in skeletal muscle fibers. Disruption of microtubules impairs long-range GLUT4 movement and decreases insulin-stimulated glucose uptake. Kinesin-1-mediated trafficking is essential for insulin-stimulated GLUT4 translocation and glucose uptake.
Article
Biochemistry & Molecular Biology
Mirko Magnone, Sonia Spinelli, Giulia Begani, Lucrezia Guida, Laura Sturla, Laura Emionite, Elena Zocchi
Summary: This study demonstrates that the plant hormone ABA can improve glycemic control and enhance muscle insulin sensitivity and glucose uptake in a murine model of T1D.
Article
Biochemistry & Molecular Biology
Amit Kumar, Malabika Datta
Summary: This study found that the long non-coding RNA (lncRNA) H19 and HDAC6 exhibit inverse expression patterns in diabetic mice and cells, and inhibition of H19 leads to increased HDAC activity and levels. This is associated with downregulation of IRS1 levels, suggesting that the H19-HDAC6 axis may regulate cellular IRS1 levels. Restoring normal H19 levels could be a potential therapeutic strategy for insulin resistance and type 2 diabetes.
MOLECULAR MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Xi Sheng Rao, Xiao Xia Cong, Xiu Kui Gao, Yin Pu Shi, Lin Jing Shi, Jian Feng Wang, Chen-Yao Ni, Ming Jie He, Yingke Xu, Cong Yi, Zhuo-Xian Meng, Jinling Liu, Peng Lin, Li Ling Zheng, Yi Ting Zhou
Summary: This study reveals that AMPK positively regulates the activation of Rab5 and identifies TBC1D17 as a GAP of Rab5, regulating Glut4 translocation in cells and muscles. TBC1D17 interacts with Rab5 or AMPK via N-Ter or TBC domain, while AMPK phosphorylates TBC1D17 at Ser 168 to enhance its auto-inhibition.
CELL DEATH AND DIFFERENTIATION
(2021)
Article
Gastroenterology & Hepatology
Anita R. Patel, Henriette Frikke-Schmidt, Olivier Bezy, Paul Sabatini, Nikolaj Rittig, Niels Jessen, Martin G. Myers, Randy J. Seeley
Summary: The study found that Lipopolysaccharide (LPS) can increase levels of GDF15 in mice, rats, and humans, but GDF15 is not necessary for inducing anorexia and weight loss in response to moderate systemic infection.
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
(2022)
Article
Nutrition & Dietetics
Mette Glavind Bulow Pedersen, Esben Sondergaard, Camilla Bak Nielsen, Mogens Johannsen, Lars Christian Gormsen, Niels Moller, Niels Jessen, Nikolaj Rittig
Summary: Oral lactate administration can directly affect the upper gastrointestinal tract, altering gut hormone secretion, motility, and appetite sensations, which cannot be solely mediated by lactate in the systemic circulation. This may have implications for the treatment of metabolic diseases.
CLINICAL NUTRITION
(2022)
Article
Biochemistry & Molecular Biology
Haoning Howard Cen, Bahira Hussein, Jose Diego Botezelli, Su Wang, Jiashuo Aaron Zhang, Nilou Noursadeghi, Niels Jessen, Brian Rodrigues, James A. Timmons, James D. Johnson
Summary: Hyperinsulinemia, often considered as a compensatory response to insulin resistance, may actually contribute to insulin resistance. The molecular mechanisms underlying this cyclic process are poorly understood. This study found a reliable negative correlation between fasting insulin and INSR mRNA in skeletal muscle. Through cell culture experiments, it was demonstrated that elevated insulin levels attenuated AKT and ERK signaling in muscle cells. RNA-sequencing analysis revealed changes in gene expression related to insulin receptor signaling, FOXO signaling, and glucose metabolism pathways. Hyperinsulinemia led to reduced Insr gene expression and decreased surface INSR protein. SIN3A was identified as a negative regulator of Insr mRNA. These findings provide insights into the mechanisms of hyperinsulinemia-induced insulin resistance in muscle.
Article
Medicine, General & Internal
Mai C. Arlien-Soborg, Jakob Dal, Michael Alle Madsen, Morten Lyng Hogild, Astrid Johannesson Hjelholt, Steen B. Pedersen, Niels Moller, Niels Jessen, Jens O. L. Jorgensen
Summary: This study investigates the molecular mechanisms of insulin resistance dissociated from obesity in patients with acromegaly. The results suggest that uncontrolled lipolysis is a major feature of insulin resistance in active acromegaly, characterized by upregulation of PTEN and suppression of insulin signaling in both muscle and fat.
Article
Endocrinology & Metabolism
Esben S. Lauritzen, Ulla Kampmann, Mette G. B. Pedersen, Lise-Lotte Christensen, Niels Jessen, Niels M-ller, Julie Stoy
Summary: The study investigated the metabolic effects of long-term melatonin treatment in patients with type 2 diabetes, revealing that melatonin treatment decreased insulin sensitivity and increased glucose-stimulated insulin secretion in male patients.
JOURNAL OF PINEAL RESEARCH
(2022)
Article
Endocrinology & Metabolism
Morten Lyng Hogild, Astrid Johannesson Hjelholt, Jakob Hansen, Steen Bonlokke Pedersen, Niels Moller, Jorgen F. P. Wojtaszewski, Mogens Johannsen, Niels Jessen, Jens Otto Lunde Jorgensen
Summary: This study reveals that administration of β-OHB can increase insulin sensitivity by suppressing lipolysis.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2023)
Article
Biochemistry & Molecular Biology
Camilla Blunk Brandt, Sofie Vestergaard Fonager, Janos Hasko, Rikke Bek Helmig, Soren Degn, Lars Bolund, Niels Jessen, Lin Lin, Yonglun Luo
Summary: This study reports a highly efficient and selection-free CRISPR gene editing approach using ribonucleoprotein (RNP) complex in primary endothelial cells (HUVECs). The optimized mRNA delivery protocol achieved nearly 100% transfection efficiency of HUVECs with EGFP mRNA. By utilizing this optimized DNA-free approach, highly efficient (98%) and biallelic HIF1A knockout in HUVECs without selection was achieved using three different gRNAs. Functional assays validated the effects of HIF1A knockout on ECs' angiogenic characteristics and response to hypoxia. This work provides a simple method for highly efficient gene editing of primary endothelial cells (HUVECs) in studies and manipulations of ECs functions.
Article
Endocrinology & Metabolism
Aleksander L. Hansen, Reimar W. Thomsen, Charlotte Brons, Helene M. L. Svane, Rasmus T. Jensen, Mette K. Andersen, Torben Hansen, Jens S. Nielsen, Peter Vestergaard, Kurt Hojlund, Niels Jessen, Michael H. Olsen, Henrik T. Sorensen, Allan A. Vaag
Summary: Low birthweight is associated with earlier onset of type 2 diabetes and lower BMI and waist circumference. Individuals with low birthweight have more comorbidities and require more medication for glucose-lowering and hypertension control.
Article
Endocrinology & Metabolism
Mai C. Arlien-Soborg, Jakob Dal, Michael Alle Madsen, Morten Lyng Hogild, Steen B. Pedersen, Niels Jessen, Jens O. L. Jorgensen, Niels Moller
Summary: Active acromegaly induces reversible changes in whole-body and skeletal muscle protein kinetics, with a decrease in whole-body protein breakdown and synthesis, and unaltered forearm muscle protein kinetics.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2023)
Article
Biochemical Research Methods
Tine Borum Billeskov, Jonas Brorson Jensen, Niels Jessen, Jean Farup
Summary: This article details the specific quantification and isolation steps for primary human fibro-adipogenic progenitors and skeletal muscle stem cells using fluorescence-activated cell sorting. It emphasizes important phenotypic traits such as time to enter the cell cycle and assessment of cell differentiation for the isolated cell populations. The technique has been applied on tissue obtained from surgery and needle biopsies.
Article
Nutrition & Dietetics
Mette Glavind Billow Pedersen, Esben Stistrup Lauritzen, Mads Vandsted Svart, Julie Stoy, Esben Sondergaard, Henrik Holm Thomsen, Ulla Kampmann, Mette Bjerre, Niels Jessen, Niels Moller, Nikolaj Rittig
Summary: LEAP2 concentration decreases after fasting and increases postprandially. Oral administration of glucose and lactate elevates LEAP2 concentration, while BHB reduces LEAP2 concentration.
AMERICAN JOURNAL OF CLINICAL NUTRITION
(2023)
Article
Pharmacology & Pharmacy
Pernille Tveden-Nyborg, Troels K. Bergmann, Niels Jessen, Ulf Simonsen, Jens Lykkesfeldt
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
(2023)
Article
Endocrinology & Metabolism
Anne Kathrine Nissen Pedersen, Lars Christian Gormsen, Soren Nielsen, Niels Jessen, Mette Bjerre
Summary: The study found that treatment with metformin in patients with type 2 diabetes can suppress circulating FAP activity, increase the expression of FGFR1c and beta-klotho, and improve the sensitivity of adipose tissue to FGF21.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2023)
Article
Geriatrics & Gerontology
A. Augusto Peluso, Agnete T. Lundgaard, Parizad Babaei, Felippe Mousovich-Neto, Andrea L. Rocha, Mads V. Damgaard, Emilie G. Bak, Thiyagarajan Gnanasekaran, Ole L. Dollerup, Samuel A. J. Trammell, Thomas S. Nielsen, Timo Kern, Caroline B. Abild, Karolina Sulek, Tao Ma, Zach Gerhart-Hines, Matthew P. Gillum, Manimozhiyan Arumugam, Cathrine Orskov, Douglas McCloskey, Niels Jessen, Markus J. Herrgard, Marcelo A. S. Mori, Jonas T. Treebak
Summary: The gut microbiota is influenced by dietary supplementation of nicotinamide riboside (NR), an NAD(+) precursor. NR altered the gut microbiota in rats and mice, leading to changes in fat and energy absorption. However, the gut microbiota of humans remained unaltered by NR supplementation. These findings suggest that the effects of NR on the gut microbiota may be species-specific.
Meeting Abstract
Public, Environmental & Occupational Health
Frederik Pagh Kristensen, Diana Christensen, Brian Callaghan, Helene Svane, Jacob Stidsen, Jens Nielsen, Kurt Hojlund, Henning Beck-Nielsen, Troels Jensen, Henning Andersen, Peter Vestergaard, Niels Jessen, Michael Olsen, Torben Hansen, Charlotte Brons, Allan Vaag, Henrik Toft Sorensen, Reimar Thomsen
PHARMACOEPIDEMIOLOGY AND DRUG SAFETY
(2022)
