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
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
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
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
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
Rafael A. Casuso, Saad Al Fazazi, Francisco J. Ruiz-Ojeda, Julio Plaza-Diaz, Ascension Rueda-Robles, Jeronimo Aragon-Vela, Jesus R. Huertas
Summary: The study tested whether supplementing hydroxytyrosol, the main polyphenol in olive oil, during exercise would modify the molecular regulators of glucose uptake. Results showed that a low-to-moderate dose of hydroxytyrosol might alter the beneficial effect of training on basal AKT phosphorylation and Rac1 activity in rats.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Article
Physiology
Arkady Uryash, Alfredo Mijares, Carlos E. Lopez, Jose A. Adams, Jose R. Lopez
Summary: Chronic elevated muscle Ca2+ levels may decrease insulin-stimulated glucose uptake, leading to hyperglycemia. By reducing muscle Ca2+ levels, muscle glucose uptake can be improved, alleviating hyperglycemia. This phenomenon may be related to the expression and subcellular fractionation of GLUT4.
FRONTIERS IN PHYSIOLOGY
(2022)
Review
Physiology
David H. Wasserman
Summary: Research conducted over the last 50 years has provided insights into the mechanisms of insulin-stimulated glucose transport in skeletal muscle cells, highlighting the importance of glucose phosphorylation by hexokinases for glucose uptake. However, the regulation of insulin-regulated hexokinase II remains poorly understood.
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
Cardiac & Cardiovascular Systems
Yang Jiao, Albert Williams, Ning Wei
Summary: This study found that Que promoted glucose uptake, inhibited oxidative stress, and improved insulin resistance through METTL3-mediated m6A modification of PRKD2 mRNA.
NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES
(2022)
Review
Endocrinology & Metabolism
Jinhee Hwang, Debbie C. Thurmond
Summary: The impaired GLUT4 translocation and defects in SNARE proteins and their regulators are closely related to the pathogenesis of diabetes. Novel functions of SNARE proteins in pathways not typically associated with SNAREs may provide new therapeutic targets for combating insulin resistance and diabetes.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Automation & Control Systems
Yara Hamshawi, Florin-Daniel Bilbie, Andrei Paun, Assaf Malka, Ron Piran
Summary: Membrane computing, a subfield of natural computing, models living systems using mathematical tools. Researchers have developed a new conceptual tool to better fit P-systems to higher-order organisms and successfully simulated glucose homeostasis in health and disease.
JOURNAL OF THE FRANKLIN INSTITUTE-ENGINEERING AND APPLIED MATHEMATICS
(2022)
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
Cell Biology
Suting Li, Zhi Wang, Mao Chen, Ya Xiao, Jie Min, Ming Hu, Jianming Tang, Li Hong
Summary: In this study, ArfGAP3 was found to be expressed during skeletal muscle injury and myoblast differentiation, and positively correlated with COPI-related genes. In vitro experiments showed that ArfGAP3 regulates COPI-associated vesicle and GLUT4 transport, impacting myoblast proliferation and differentiation by influencing glucose uptake. These findings provide insight into the repair process after skeletal muscle injury.
CELLULAR SIGNALLING
(2023)
Article
Biochemistry & Molecular Biology
Atsushi Sudo, Motoi Kanagawa, Mai Kondo, Chiyomi Ito, Kazuhiro Kobayashi, Mitsuharu Endo, Yasuhiro Minami, Atsu Aiba, Tatsushi Toda
HUMAN MOLECULAR GENETICS
(2018)
Article
Multidisciplinary Sciences
Yusuke Sakai, Hidetoshi Kassai, Hisako Nakayama, Masahiro Fukaya, Tatsuya Maeda, Kazuki Nakao, Kouichi Hashimoto, Hiroyuki Sakagami, Masanobu Kano, Atsu Aiba
SCIENTIFIC REPORTS
(2019)
Article
Dermatology
Takehiko Ueyama, Megumi Sakuma, Mio Nakatsuji, Tatsuya Uebi, Takeshi Hamada, Atsu Aiba, Naoaki Saito
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2020)
Article
Multidisciplinary Sciences
Harumi Nakao, Yasushi Kishimoto, Kouichi Hashimoto, Kazuo Kitamura, Miwako Yamasaki, Kazuki Nakao, Masahiko Watanabe, Masanobu Kano, Yutaka Kirino, Atsu Aiba
SCIENTIFIC REPORTS
(2019)
Article
Multidisciplinary Sciences
Wakako Kumita, Kenya Sato, Yasuhiro Suzuki, Yoko Kurotaki, Takeshi Harada, Yang Zhou, Noriyuki Kishi, Kengo Sato, Atsu Aiba, Yasubumi Sakakibara, Guoping Feng, Hideyuki Okano, Erika Sasaki
SCIENTIFIC REPORTS
(2019)
Article
Cell Biology
Kenichiro Nagahama, Kazuto Sakoori, Takaki Watanabe, Yusuke Kishi, Keita Kawaji, Michinori Koebis, Kazuki Nakao, Yukiko Gotoh, Atsu Aiba, Naofumi Uesaka, Masanobu Kano
Article
Biochemistry & Molecular Biology
Layla Kawarada, Masahiro Fukaya, Ryo Saito, Hidetoshi Kassai, Hiroyuki Sakagami, Atsu Aiba
Summary: ALKBH1 plays critical roles in the hippocampus, and its deficiency results in mitochondrial dysfunction, hippocampal abnormalities, and impaired hippocampus-dependent learning.
Article
Neurosciences
Ryo Saito, Chika Miyoshi, Michinori Koebis, Itaru Kushima, Kazuki Nakao, Daisuke Mori, Norio Ozaki, Hiromasa Funato, Masashi Yanagisawa, Atsu Aiba
Summary: The study generated two mouse models mimicking 22q11.2DS, finding that the 1.4-Mb deletion mice exhibited decreased locomotor activity, while the 1.5-Mb deletion mice showed impairment in prepulse inhibition and fear memory. This suggests that impaired social recognition observed in mice mimicking the human 3.0-Mb deletion requires mutations in both the 1.4-Mb and 1.5-Mb regions.
Article
Biochemistry & Molecular Biology
Kiko Hasegawa, Nobuyuki Takenaka, Kenya Tanida, Man Piu Chan, Mizuki Sakata, Atsu Aiba, Takaya Satoh
Summary: Rac1 is involved in insulin-dependent glucose uptake and lipogenesis in white adipocytes, and its deficiency may result in reduced insulin responsiveness and atrophy of white adipose tissues.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Yukiko Abe, Harumi Nakao, Motoki Goto, Moe Tamano, Michinori Koebis, Kazuki Nakao, Atsu Aiba
Summary: Genetic engineering of common marmosets using AET and CRISPR/Cas9 systems has been developed as an efficient method to produce mutant animals, reducing the time for in vitro embryo culture. This method uses an embryo donor as the recipient, minimizing the number of animals used and aligning with the 3R principles of humane experimental technique.
SCIENTIFIC REPORTS
(2021)
Article
Neurosciences
Keita Mori, Michinori Koebis, Kazuki Nakao, Shizuka Kobayashi, Yuji Kiyama, Masahiko Watanabe, Toshiya Manabe, Yuichi Iino, Atsu Aiba
Summary: This study investigates the function of Calsyntenins (CLSTNs) by generating triple knockout (TKO) mice lacking all CLSTN paralogs. The mutant mice exhibited freezing behavior in novel environments and hypersensitivity to stress. Glucose levels under stress were significantly higher in the mutant mice than in the wild-type controls. Phenotypes such as decreased motivation, which had not been reported in single Clstn knockout mice, were newly discovered. The TKO mice generated in this study serve as an important mouse model for further understanding the function of CLSTN.
Article
Cell Biology
Maria Harbers, Harumi Nakao, Takaki Watanabe, Kyoko Matsuyama, Shoichi Tohyama, Kazuki Nakao, Yasushi Kishimoto, Masanobu Kano, Atsu Aiba
Summary: mGluR1 and mGluR5 show complementary distributions in the central nervous system. The study on mGluR5-rescue mice suggests that mGluR5 functions comparably to mGluR1 in cerebellar Purkinje cells.
Article
Multidisciplinary Sciences
Yasuko O. Abe, Hikari Yoshitane, Dae Wook Kim, Satoshi Kawakami, Michinori Koebis, Kazuki Nakao, Atsu Aiba, Jae Kyoung Kim, Yoshitaka Fukada
Summary: This study identifies the critical role of a secondary feedback loop in the mammalian circadian clock, which works in conjunction with the core loop to establish a disturbance-resistant clock system.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Kiko Hasegawa, Nobuyuki Takenaka, Maaya Yamamoto, Yoshiki Sakoda, Atsu Aiba, Takaya Satoh
Summary: White adipocytes play a vital role in energy balance by storing lipids. The small GTPase Rac1 is involved in regulating insulin-stimulated glucose uptake in white adipocytes. In this study, we used in vitro differentiation systems to investigate the abnormal development of Rac1-deficient white adipocytes. Rac1-deficient adipocytes showed significantly reduced lipid droplet formation and inhibition of enzymes responsible for fatty acid and triacylglycerol synthesis. Transcription factors involved in lipogenic enzyme induction were also inhibited in Rac1-deficient cells. These results suggest that Rac1 is crucial for adipogenic differentiation and lipogenesis by regulating differentiation-related transcription.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Ippei Kikuchi, Yusuke Iwashita, Atsushi Takahashi-Kanemitsu, Michinori Koebis, Atsu Aiba, Masanori Hatakeyama
Summary: Researchers generated BFK triple-knockout mice and found that they exhibited impaired intestinal homeostasis, including a reduced stem/progenitor cell population and defective recovery from radiation-induced mucosal damage, specifically in the ileum. RNA-seq analysis revealed elevated IL-22/STAT3 signaling and altered composition of the ileal microbiota in BFK/TKO mice. BFKs may redundantly confer robust homeostasis to the ileum, which plays crucial roles in nutrient absorption and mucosal immunity.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)