Article
Endocrinology & Metabolism
Lucie Yammine, Belen Picatoste, Nazish Abdullah, Rosemary A. Leahey, Emma F. Johnson, Nicolas Gomez-Banoy, Carolina Rosselot, Jennifer Wen, Tahmina Hossain, Marcus D. Goncalves, James C. Lo, Adolfo Garcia-Ocana, Timothy E. McGraw
Summary: This study generated mouse models of GIPR-Q354 and GIPR-E354 using CRISPR-CAS9 editing and found that GIPR-Q350 mice show differences in weight, diet-induced obesity resistance, and glucose tolerance. The study also discovered the impact of GIPR-Q354 variant on metabolism in pancreatic islets and β-cells. These findings contribute to a better understanding of the influence of GIPR-Q354 variant on glucose homeostasis and potentially provide new targets for pharmacologic treatment of metabolic diseases.
MOLECULAR METABOLISM
(2023)
Article
Cell Biology
Julia K. Panzer, Alejandro Tamayo, Alejandro Caicedo
Summary: This study identifies a defect in autocrine signaling in pancreatic alpha cells of individuals with type 1 diabetes, which leads to inadequate glucagon response and susceptibility to hypoglycemia. Reactivating residual AMPA/kainate receptor function with positive allosteric modulators can restore normal glucagon secretion and prevent hypoglycemia, providing a potential therapeutic approach for managing diabetes.
Article
Endocrinology & Metabolism
Henriette H. Nerild, Andreas Bronden, Ida M. Gether, Pernille H. Hellmann, Mille Baekdal, Matthew P. Gillum, Jens S. Svenningsen, Bolette Hartmann, Naveen Rathor, Hanna Angelene Kudiyanur Muniraju, Jens F. Rehfeld, Jens J. Holst, Tina Vilsboll, David P. Sonne, Filip K. Knop
Summary: In this study, it was found that Liraglutide treatment is associated with gallbladder-related disorders and can delay postprandial gallbladder refilling. The gut hormones CCK, FGF19, and GLP-2, which regulate gallbladder motility, may be implicated in these disorders.
DIABETES OBESITY & METABOLISM
(2023)
Review
Biochemistry & Molecular Biology
Anastasia N. Vaganova, Taisiia S. Shemyakova, Karina V. Lenskaia, Roman N. Rodionov, Charlotte Steenblock, Raul R. Gainetdinov
Summary: Currently, the treatment of metabolic syndrome primarily focuses on pharmacological symptom relief and complex lifestyle changes. This study explores the role of trace amines and their receptor systems, particularly trace amine-associated receptor 1 (TAAR1), in the pathogenesis of metabolic syndrome and the regulation of insulin secretion in pancreatic islets. The findings suggest that TAAR1 agonists have a positive effect on the progression of metabolic syndrome and the development of related diseases. Additionally, the expression of TAARs and the deregulation of their functional associations were found to be different in patients with metabolic diseases compared to healthy donors, indicating their potential as therapeutic targets.
Article
Endocrinology & Metabolism
Harshal A. Deshmukh, Anne Lundager Madsen, Ana Vinuela, Christian Theil Have, Niels Grarup, Andrea Tura, Anubha Mahajan, Alison J. Heggie, Robert W. Koivula, Federico De Masi, Konstantinos K. Tsirigos, Allan Linneberg, Thomas Drivsholm, Oluf Pedersen, Thorkild I. A. Sorensen, Arne Astrup, Anette A. P. Gjesing, Imre Pavo, Andrew R. Wood, Hartmut Ruetten, Angus G. Jones, Anitra D. M. Koopman, Henna Cederberg, Femke Rutters, Martin Ridderstrale, Markku Laakso, Mark McCarthy, Tim M. Frayling, Ele Ferrannini, Paul W. Franks, Ewan R. Pearson, Andrea Mari, Torben Hansen, Mark Walker
Summary: Through a genome-wide meta-analysis, we have identified variations in the GIPR-QPCTL and CDKAL1 loci as key determinants of pancreatic beta-cell glucose sensitivity. These results indicate that genetic variations play a significant role in regulating beta-cell glucose sensitivity.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2021)
Article
Biochemistry & Molecular Biology
Peng Jiang, Lejiao Ren, Li Zhi, Zhong Yu, Fengxiang Lv, Fengli Xu, Wei Peng, Xiaoyu Bai, Kunlun Cheng, Li Quan, Xiuqin Zhang, Xianhua Wang, Yan Zhang, Dan Yang, Xinli Hu, Rui-Ping Xiao
Summary: High glucose suppresses AMPK signaling through MG53-mediated AMPK alpha degradation and deactivation, as well as ROS-dependent inhibition of AMPK alpha phosphorylation at T172. These findings elucidate the mechanism of impaired AMPK signaling in overnutrition-related diseases and underscore the importance of maintaining the yin-yang balance of AMPK signaling for metabolic homeostasis.
Article
Plant Sciences
Prawej Ansari, Peter R. Flatt, Patrick Harriott, J. M. A. Hannan, Yasser H. A. Abdel-Wahab
Summary: The study demonstrated the antidiabetic effects of Acacia arabica bark extract, showing potential as a treatment for diabetes. The isolated phytoconstituents, including quercetin and kaempferol, improved glucose tolerance and insulin secretion, indicating the benefits of using them as antidiabetic agents.
Article
Endocrinology & Metabolism
Mohammad Tariq, Arnaldo H. H. de Souza, Mohammed Bensellam, Heeyoung Chae, Manon Jaffredo, Anne-Francoise Close, Jean-Philippe Deglasse, Laila R. B. Santos, Antoine Buemi, Nizar I. I. Mourad, Anne Wojtusciszyn, Matthieu Raoux, Patrick Gilon, Christophe Broca, Jean-Christophe Jonas
Summary: Prolonged culture of human islets under moderate to severe glucotoxic conditions markedly increased their glucose sensitivity and revealed a bell-shaped acute glucose response curve for changes in [Ca2+](c) and insulin secretion, with maximal stimulation at 5 or 10 mmol/l glucose and rapid inhibition above that concentration. This novel glucotoxic alteration may contribute to beta cell dysfunction in type 2 diabetes independently from a detectable increase in beta cell apoptosis.
Article
Food Science & Technology
Xiaotong Su, Shun Hao, Wenna Li, Xu Li, Zhentao Mo, Yiqi Li, Lu Xiao, Wenjun Wang, Feng Wang
Summary: Obesity is linked to an increased risk of chronic diseases and negatively impacts overall quality of life. Gardenia jasminoides (Ellis) fruit (GE) and Eucommia ulmoides leaves (EE) are traditional medicines with reported antioxidative, anti-hyperglycemic, anti-hyperlipidemic, and anti-obesity properties. However, the combined effect of GE and EE is still unknown. This study aimed to investigate this combination through animal and cell experiments.
JOURNAL OF FUNCTIONAL FOODS
(2023)
Review
Endocrinology & Metabolism
Yu-Feng Zhao
Summary: This article introduces the effects of FFA receptors on glucose metabolism and the underlying hormonal gastrointestinal-pancreatic-adipose interactions and intracellular mechanisms. It also summarizes the development of therapeutic drugs targeting FFA receptors for the treatment of abnormal glucose metabolism such as type 2 diabetes mellitus.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Neurosciences
Jingwen Li, Jonas R. Knudsen, Carlos Henriquez-Olguin, Zhencheng Li, Jesper B. Birk, Kaspar W. Persson, Ylva Hellsten, Anika Offergeld, William Jarassier, Fabien Le Grand, Peter Schjerling, Jorgen F. P. Wojtaszewski, Thomas E. Jensen
Summary: AXIN1 imKO does not affect whole-body energy metabolism, AMPK/mTORC1 signaling, or glucose uptake in skeletal muscle, showing only differences in exercising gastrocnemius muscle.
JOURNAL OF PHYSIOLOGY-LONDON
(2021)
Article
Multidisciplinary Sciences
Maria F. Rubin de Celis, Ruben Garcia-Martin, Ismail Syed, Jennifer Lee, Cristina Aguayo-Mazzucato, Susan Bonner-Weir, Barbara B. Kahn
Summary: Senescence in pancreatic beta cells contributes to beta cell dysfunction and diabetes. Treatment with PAHSAs, a novel class of endogenous lipids, can delay and reduce the incidence of autoimmune diabetes in NOD mice by preventing and reversing metabolic stress-induced senescence. This protective effect is achieved through multiple mechanisms, including increased expression of Mdm2, DNA repair genes, glutathione metabolism genes, and promotion of autophagy. These findings suggest that PAHSAs may offer similar benefits in humans.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Ryan Fitzgerald, Andrew Olsen, Jessica Nguyen, Winifred Wong, Malek El Muayed, Joshua Edwards
Summary: This study found that islets isolated from animals treated with cadmium for 12 weeks had significantly reduced insulin release in response to glucose stimulation, with selective accumulation of cadmium in pancreatic islets leading to altered islet function and potentially contributing to dysglycemia.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Uma D. Kabra, Charles Affourtit, Martin Jastroch
Summary: The development of obesity and type 2 diabetes is associated with impaired mitochondrial function and abnormal insulin secretion in pancreatic beta cells. Assessment of mitochondrial bioenergetic parameters with Seahorse extracellular flux technology can predict insulin secretion. High-fat feeding in mice led to decreased glucose sensitivity in islet respiration, highlighting the importance of mitochondrial function in regulating insulin secretion.
Article
Biochemistry & Molecular Biology
Dorota Rogacka, Irena Audzeyenka, Patrycja Rachubik, Maria Szrejder, Marlena Typiak, Stefan Angielski, Agnieszka Piwkowska
Summary: In hyperglycemic conditions, the interaction between the protein deacetylase SIRT1 and adenosine monophosphate-dependent protein kinase (AMPK) in glomerular podocytes is altered. Modulating the NO synthase (NOS) / NO pathway can improve SIRT1 and AMPK activity, consequently enhancing glucose uptake.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2021)
Article
Cell Biology
Chutima Charoensuk, Prapaporn Jungtrakoon Thamtarana, Chutima Chanprasert, Watip Tangjittipokin, Jun Shirakawa, Yu Togashi, Kazuki Orime, Pucharee Songprakhon, Chartchai Chaichana, Zuroida Abubakar, Paweena Ouying, Jatuporn Sujjitjoon, Alessandro Doria, Nattachet Plengvidhya, Pa-thai Yenchitsomanus
Summary: This study reveals a missense mutation in the ZYG11A gene associated with hyperglycemia in a family, suggesting its crucial role in beta-cell growth. The findings indicate that the ZYG11A mutation may predispose obese individuals to beta-cell failure and impact glucose homeostasis maintenance.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2021)
Article
Multidisciplinary Sciences
Tomoko Okuyama, Jun Shirakawa, Takashi Nakamura, Takayo Murase, Daisuke Miyashita, Ryota Inoue, Mayu Kyohara, Yu Togashi, Yasuo Terauchi
Summary: The study found that XOR activity is correlated with clinical and metabolic parameters in patients with type 2 diabetes, as well as cardiovascular complications. XOR activity may serve as a potential marker for the development of vascular complications, liver dysfunction, and insulin resistance in T2DM.
SCIENTIFIC REPORTS
(2021)
Review
Biochemistry & Molecular Biology
Tomoko Okuyama, Mayu Kyohara, Yasuo Terauchi, Jun Shirakawa
Summary: IGFs mainly mediate long-term actions in cell fates, while insulin predominantly exerts its role on metabolic activities. The interactions between insulin receptor signaling and IGF-I receptor signaling in metabolism and cell fates are complicated, and the function of IGF-I in respective tissues remains insufficiently understood. Clarifying the precise roles of IGF-I signaling on metabolism separate from those of insulin signaling is necessary.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Editorial Material
Endocrinology & Metabolism
Jun Shirakawa
Summary: Recent reports highlight the potential direct infection of beta-cells by SARS-CoV-2 and the impact on diabetes patients under COVID-19. Developing more effective therapeutic strategies remains crucial in the fight against the virus.
JOURNAL OF DIABETES INVESTIGATION
(2021)
Article
Endocrinology & Metabolism
Sakiko Terui, Ryoichi Akamatsu, Masanori Arai, Ryota Inoue, Tomoko Okuyama, Mayu Kyohara, Jinghe Li, Takahiro Tsuno, Daisuke Miyashita, Yu Togashi, Yasuo Terauchi, Jun Shirakawa
Summary: Dulaglutide, a long-acting GLP-1 receptor agonist, can reduce glucose levels within 24 hours after the first injection in patients with type 2 diabetes, maintaining stable improvements in glucose levels for a week in a hospitalized clinical setting. The drug also improves patients' glucose levels, especially for those without cerebrovascular disease and diabetic retinopathy.
Article
Endocrinology & Metabolism
Jinghe Li, Ryota Inoue, Yu Togashi, Tomoko Okuyama, Aoi Satoh, Mayu Kyohara, Kuniyuki Nishiyama, Takahiro Tsuno, Daisuke Miyashita, Tatsuya Kin, A. M. James Shapiro, Resilind Su Ern Chew, Adrian Kee Keong Teo, Seiichi Oyadomari, Yasuo Terauchi, Jun Shirakawa
Summary: Imeglimin protects beta-cell survival by enhancing function, promoting proliferation, and preventing apoptosis, thereby improving islet survival and mass.
Article
Endocrinology & Metabolism
Taichi Minami, Jun Shirakawa, Hiroko Hiiragi, Taku Yamada, Youichi Suzuki, Shinitiro Shirabe, Hajime Maeda, Yasuo Terauchi
Summary: The study developed and evaluated a Japanese version of the diabetes knowledge test for in-patients with type 2 diabetes, and found that the test scores significantly increased after the education programs. The J-DKT demonstrated acceptable reliability and validity in assessing patients' knowledge levels.
JOURNAL OF DIABETES INVESTIGATION
(2022)
Article
Biochemistry & Molecular Biology
Mitsuaki Sobajima, Masato Miyake, Yoshimasa Hamada, Kazue Tsugawa, Miho Oyadomari, Ryota Inoue, Jun Shirakawa, Hiroshi Arima, Seiichi Oyadomari
Summary: The stress-inducible transcription factor ATF4 is crucial for the survival and identity of beta-cells during stress conditions. Its role in glucose-stimulated insulin secretion (GSIS) was investigated using beta-cell-specific Atf4 knockout mice. The results showed that ATF4 is essential for insulin production and glucose-stimulated ATP and cAMP production, contributing to the multifaceted regulatory process in GSIS.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Review
Biochemical Research Methods
Hisashi Hirano, Jun Shirakawa
Summary: Phos-tag electrophoresis is an important method for analyzing the phosphorylation state of proteins. The recently developed Phos-tag diagonal electrophoresis has overcome the drawbacks of the traditional method and made it easier to determine protein phosphorylation state.
EXPERT REVIEW OF PROTEOMICS
(2022)
Article
Endocrinology & Metabolism
Florencia Halperin, Teresa Mezza, Ping Li, Jun Shirakawa, Rohit N. Kulkarni, Allison B. Goldfine
Summary: This study investigates the regulatory role of insulin in the beta cell response to arginine stimulation in healthy humans. The results demonstrate that pre-exposure to insulin enhances arginine-stimulated insulin secretion. This finding reveals the physiological role of insulin in regulating beta cell response to non-glucose secretagogues.
METABOLISM-CLINICAL AND EXPERIMENTAL
(2022)
Article
Endocrinology & Metabolism
Yu Togashi, Daisuke Miyashita, Takahiro Tsuno, Ryota Inoue, Tomoko Okuyama, Mayu Kyohara, Kuniyuki Nishiyama, Masanori Arai, Kenta Kanematsu, Soichiro Kanataki, Yasuo Terauchi, Jun Shirakawa
Summary: This study aimed to clarify the relationship between abdominal aortic calcification (AAC) grade and cardiovascular diseases in individuals with type 2 diabetes mellitus. The study found that AAC score was significantly correlated with coronary artery disease (CAD) and cerebral infarction (CI) in individuals with type 2 diabetes mellitus. Low body mass index (BMI) and Fibrosis-4 (Fib-4) index >2.67 were valuable indicators of AAC in people with type 2 diabetes mellitus.
JOURNAL OF DIABETES INVESTIGATION
(2022)
Article
Multidisciplinary Sciences
Ryota Inoue, Takahiro Tsuno, Yu Togashi, Tomoko Okuyama, Aoi Sato, Kuniyuki Nishiyama, Mayu Kyohara, Jinghe Li, Setsuko Fukushima, Tatsuya Kin, Daisuke Miyashita, Yusuke Shiba, Yoshitoshi Atobe, Hiroshi Kiyonari, Kana Bando, A. M. James Shapiro, Kengo Funakoshi, Rohit N. Kulkarni, Yasuo Terauchi, Jun Shirakawa
Summary: This study highlights the molecular link between the increase in UCP2 expression in beta-cells and beta-cell failure, and suggests that targeting the UCP2/AldB axis may be a promising approach for the recovery of beta-cell function.
Article
Cell Biology
Jun Shirakawa, Yu Togashi, Giorgio Basile, Tomoko Okuyama, Ryota Inoue, Megan Fernandez, Mayu Kyohara, Dario F. De Jesus, Nozomi Goto, Wei Zhang, Takahiro Tsuno, Tatsuya Kin, Hui Pan, Jonathan M. Dreyfuss, A. M. James Shapiro, Peng Yi, Yasuo Terauchi, Rohit N. Kulkarni
Summary: This study investigates the replication pathways of β cells under acute insulin resistance and identifies the involvement of insulin-independent factors CENP-A and transcription factor E2F1 in the multiplication of β cells induced by S961. Inhibition of E2F1 blocks β-cell proliferation in S961-injected mice. Furthermore, adipocytes activate E2F1 to promote β-cell replication.
Article
Multidisciplinary Sciences
Mayu Kyohara, Daisuke Miyashita, Ryota Inoue, Kuniyuki Nishiyama, Takahiro Tsuno, Tomoko Okuyama, Yu Togashi, Yasuo Terauchi, Jun Shirakawa
Summary: This study found that serum SerpinB1 levels in patients with T2DM are associated with insulin sensitivity and blood glucose levels.
Article
Biochemistry & Molecular Biology
Tomozumi Takatani, Jun Shirakawa, Kimitaka Shibue, Manoj K. Gupta, Hyunki Kim, Shusheng Lu, Jiang Hu, Morris F. White, Robert T. Kennedy, Rohit N. Kulkarni
Summary: This study shows that IRS1, instead of IRS2, plays a dominant role in regulating pancreatic alpha cell function. Knockout of IRS1 resulted in glucose intolerance and inappropriate glucagon secretion, while knockout of IRS2 did not lead to these abnormalities.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
