Article
Nutrition & Dietetics
Ciro Menale, Giovanna Trinchese, Immacolata Aiello, Giulia Scalia, Monica Dentice, Maria Pina Mollica, Nal Ae Yoon, Sabrina Diano
Summary: In this study, it was found that the addition of non-lipotoxic levels of 25 μM palmitic acid (PA) to glucose (G) increased mineralization in osteoblasts (OBs). It was also discovered that G+25 μM PA reduced mitochondria size in OBs and increased mitochondria respiration and ATP production, as well as the expression of oxidative phosphorylation genes. Treatment with the mitochondrial fission inhibitor Mdivi-1 reduced osteogenesis and mitochondrial respiration in OBs.
Article
Biology
Sandy MacMillan, Andrew P. Holmes, Mark L. Dallas, Amira D. Mahmoud, Michael J. Shipston, Chris Peers, D. Grahame Hardie, Prem Kumar, A. Mark Evans
Summary: This study reveals that LBK1 is a critical regulator of carotid body chemosensing, highlighting a difference in dependency on LKB1 and AMPK between the carotid body and the hypoxic ventilatory response.
COMMUNICATIONS BIOLOGY
(2022)
Article
Environmental Sciences
Xiaoyu Duan, Weijie Sun, Hongwen Sun, Lianying Zhang
Summary: The study revealed that PFASs adversely affect insulin secretion, with exposure to PFOS inhibiting SIRT1 activity and leading to impairment of GSIS.
ENVIRONMENTAL POLLUTION
(2021)
Article
Medicine, Research & Experimental
Adriano Cleis Arruda, Alexandre Budu, Thiago Nunes de Menezes, Michael Bader, Ronaldo Carvalho Araujo, Leandro Ceotto Freitas-Lima
Summary: The kinin B1 receptor (B1R) modulates mitochondrial activity under fasting and voluntary exercise conditions, reducing VO2 expenditure and heat production. B1KO animals showed a preference for lipids as an energy source and exhibited increased beta-oxidation. Lack of B1R did not induce mitochondrial activity and biogenesis, suggesting interference in metabolism responsiveness controlled by sirtuins under PGC-1 alpha control.
Article
Chemistry, Inorganic & Nuclear
Sara Chirayil, Veronica Clavijo Jordan, Andre F. Martins, Namini Paranawithana, S. James Ratnakar, A. Dean Sherry
Summary: The Mn(II)-based zinc-sensitive MRI contrast agent MnPyC3A-BPEN has shown superior kinetic inertness and stability compared to GdDTPA, making it a reliable alternative for detecting glucose-stimulated zinc secretion in the pancreas and prostate.
INORGANIC CHEMISTRY
(2021)
Article
Medicine, Research & Experimental
Feiye Zhou, Linlin Zhang, Kecheng Zhu, Mengyao Bai, Yuqing Zhang, Qin Zhu, Shushu Wang, Chunxiang Sheng, Miaomiao Yuan, Yun Liu, Jieli Lu, Li Shao, Xiao Wang, Libin Zhou
Summary: SIRT2 plays a crucial role in glucose homeostasis by regulating insulin secretion and glucose tolerance; its deficiency inhibits GSIS by affecting the degradation of GKRP and ALDOA proteins; SIRT2 overexpression enhances insulin secretion through deacetylation of GKRP in beta-cells and promoting its degradation.
Article
Biochemistry & Molecular Biology
Siresha Bathina, Tumininu S. Faniyan, Lauren Bainbridge, Autumn Davis, Kavaljit H. Chhabra
Summary: The role of beta-cell Glut2 in regulating insulin secretion and blood glucose levels in mice was investigated in this study. Knocking down Glut2 specifically in beta-cells did not affect glucose-stimulated insulin secretion and systemic glucose homeostasis in mice.
Article
Plant Sciences
Dahae Lee, Ji-Young Kim, Hak Cheol Kwon, Jaeyoung Kwon, Dae Sik Jang, Ki Sung Kang
Summary: In this study, the potential effects of alpha-Spinasterol, a phytosterol isolated from Aster pseudoglehnii, on glucose uptake and insulin secretion in skeletal muscle cells and pancreatic beta-cells were investigated. The results showed that alpha-Spinasterol enhanced glucose uptake and insulin secretion without causing any toxic effects on the cells. It also increased the expression of proteins related to glucose metabolism. These findings suggest that alpha-Spinasterol could be a potential candidate for the treatment of type 2 diabetes.
Article
Biochemistry & Molecular Biology
Guillaume Bastin, Lemieux Luu, Battsetseg Batchuluun, Alexandra Mighiu, Stephanie Beadman, Hangjung Zhang, Changhao He, Dana Al Rijjal, Michael B. Wheeler, Scott P. Heximer
Summary: RGS4 protein plays a crucial role in regulating insulin secretion in response to glucose stimulation, with its deficiency leading to impaired insulin secretion, reduced cAMP/PKA activity, and abnormal calcium oscillations in pancreatic beta-cells. These findings highlight the significance of maintaining normal levels of RGS4 function for proper insulin secretion in healthy pancreatic tissues.
Review
Biochemistry & Molecular Biology
Uma D. Kabra, Martin Jastroch
Summary: Mitochondria play vital roles in cellular energy metabolism, shape and function maintenance, and disease development, especially in the metabolism-secretion coupling of pancreatic beta cells. Disruption of mitochondrial dynamics can lead to defects in energy production and increased apoptosis, impairing insulin secretion and beta cell survival.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Endocrinology & Metabolism
Minami Kosuda, Midori Yamana, Akiko Nagasawa, Aya Tanaka, Kentaro Watanabe, Hisamitsu Ishihara
Summary: This study revealed that mitochondrial CA VB and cytosolic CA XIII are significantly increased in highly glucose-responsive insulin-secreting cells, while cytosolic CA XI is decreased. Overexpression of CA VB increases insulin secretion, while overexpression of CA XIII and CA XI has no effect on insulin secretion.
JOURNAL OF BIOLOGICAL REGULATORS AND HOMEOSTATIC AGENTS
(2023)
Article
Endocrinology & Metabolism
Cihan Atila, Odile Gaisl, Deborah R. Vogt, Laura Werlen, Gabor Szinnai, Mirjam Christ-Crain
Summary: The study demonstrates that glucagon stimulates copeptin release, and copeptin response can be used to differentiate between different forms of diabetes insipidus and primary polydipsia.
EUROPEAN JOURNAL OF ENDOCRINOLOGY
(2022)
Article
Endocrinology & Metabolism
M. Deepa Maheshvare, Soumyendu Raha, Matthias Koenig, Debnath Pal
Summary: The pancreas plays a critical role in regulating glucose homeostasis through hormone secretion. A systematic modeling workflow was used to develop a kinetic model of glucose-stimulated insulin secretion (GSIS) in the pancreatic β-cell. The model includes detailed glycolysis and phenomenological equations for insulin secretion, and it is based on experimental and clinical data from various studies.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Dahae Lee, Young-Mi Kim, Hyun Woo Kim, You-Kyoung Choi, Bang Ju Park, Sang Hoon Joo, Ki Sung Kang
Summary: Schisandrol A and schisandrin C enhanced insulin secretion and glucose uptake, with schisandrin C showing superior effects compared to gliclazide. Treatment with schisandrin C resulted in increased expression of associated proteins in cells, potentially benefiting in improving hyperglycemia.
Article
Plant Sciences
Dahae Lee, Ki Hyun Kim, Taesu Jang, Ki Sung Kang
Summary: The phytochemical examination of Cornus walteri led to the isolation of a tirucallane triterpenoid, (-)-leucophyllone, which was found to increase glucose-stimulated insulin secretion in rat INS-1 pancreatic beta-cells. Treatment with (-)-leucophyllone also resulted in increased expression of proteins related to insulin signaling, suggesting its potential as an antidiabetic agent.
Article
Cardiac & Cardiovascular Systems
Uri Pollak, Hai Zemmour, Elior Shaked, Judith Magenheim, Ori Fridlich, Amit Korach, Alain E. Serraf, David Mishaly, Benjamin Glaser, Ruth Shemer, Yuval Dor
Summary: This study investigated the use of DNA methylation markers to monitor cardiac damage after open-heart surgery. The results showed an increase in cardiac cell-free DNA (cfDNA) concentration after surgery, which then declined in most patients. The concentration of cardiac cfDNA post-surgery correlated with the duration of cardiopulmonary bypass (CPB) and aortic cross clamping. Interestingly, cardiac cfDNA at 6 hours after surgery was found to be a better predictor of mechanical ventilation duration and vasoactive-inotropic score than maximal troponin levels. Therefore, cardiac cfDNA can be used to monitor cardiac cell death, predict surgical outcomes, and evaluate the effectiveness of cardioprotective interventions.
JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH
(2023)
Review
Cell Biology
Roy Anindya, Guy A. Rutter, Gargi Meur
Summary: In this article, the dynamic interaction between pancreatic beta cells, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the host immune system in new-onset type 1 diabetes (T1D) is detailed. It is shown that beta cells express the necessary receptors for SARS-CoV-2 entry and can be infected. However, beta cell expansion and regeneration may effectively compensate for lost beta cells. The appearance of islet autoantibodies following SARS-CoV-2 infection suggests a breakdown of immune tolerance, but many cases also indicate a progression of pre-existing diabetes rather than new-onset T1D.
IMMUNOLOGY AND CELL BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Julia Ast, Daniela Nasteska, Nicholas H. F. Fine, Daniel J. Nieves, Zsombor Koszegi, Yann Lanoiselee, Federica Cuozzo, Katrina Viloria, Andrea Bacon, Nguyet T. Luu, Philip N. Newsome, Davide Calebiro, Dylan M. Owen, Johannes Broichhagen, David J. Hodson
Summary: The authors generated mice with an enzyme self-label genome-edited into the endogenous glucagon-like peptide-1 receptor locus, designed fluorescent dyes for specific labeling in complex tissue, and revealed the localization, organization, and dynamics of endogenous GLP1R in cells and tissue. These results not only demonstrate the utility of enzyme self-labels for visualization and interrogation of endogenous proteins, but also provide insights into the biology of class B GPCRs.
NATURE COMMUNICATIONS
(2023)
Article
Medicine, Research & Experimental
Nicola Romano, Chrystel Lafont, Pauline Campos, Anne Guillou, Tatiana Fiordelisio, David J. Hodson, Patrice Mollard, Marie Schaeffer
Summary: Central integration of peripheral appetite-regulating signals is crucial for maintaining energy homeostasis. This study investigated the role of median eminence mural cells in modulating gut hormone effects on feeding behavior. The findings suggest that activation of these vascular cells can alter blood flow velocity, delaying the access of ghrelin to target neurons and thereby modulating food intake in response to peripheral ghrelin.
Article
Endocrinology & Metabolism
Parizad Avari, Pei Chia Eng, Ming Hu, Runzhi Chen, Natalija Popovic, Constantin Polychronakos, Duncan Spalding, Guy A. Rutter, Nick Oliver, Florian Wernig
Summary: This article reports a case of a proinsulinoma with suppressed insulin and C-peptide levels. It suggests that low insulin and C-peptide levels do not always indicate the absence of a neuroendocrine islet cell tumor, and elevated proinsulin levels may be an indicator for diagnosis.
JOURNAL OF THE ENDOCRINE SOCIETY
(2023)
Article
Medicine, Research & Experimental
Pauline Chabosseau, Fiona Yong, Luis F. Delgadillo-Silva, Eun Young Lee, Rana Melhem, Shiying Li, Nidhi Gandhi, Jules Wastin, Livia Lopez Noriega, Isabelle Leclerc, Yusuf Ali, Jing W. Hughes, Robert Sladek, Aida Martinez-Sanchez, Guy A. Rutter
Summary: Spatially-organized increases in Ca2+ within pancreatic beta cells under high glucose stimulation were found to be mediated by leader cells, which possess unique molecular features and localized signaling with delta cells. Single cell RNA sequencing revealed differential gene expression related to cilium biogenesis and transcriptional regulation between leader and follower cells.
Article
Multidisciplinary Sciences
Roderick C. Slieker, Louise A. Donnelly, Elina Akalestou, Livia Lopez-Noriega, Rana Melhem, Aysim Gunes, Frederic Abou Azar, Alexander Efanov, Eleni Georgiadou, Hermine Muniangi-Muhitu, Mahsa Sheikh, Giuseppe N. Giordano, Mikael Akerlund, Emma Ahlqvist, Ashfaq Ali, Karina Banasik, Soren Brunak, Marko Barovic, Gerard A. Bouland, Frederic Burdet, Mickael Canouil, Iulian Dragan, Petra J. M. Elders, Celine Fernandez, Andreas Festa, Hugo Fitipaldi, Phillippe Froguel, Valborg Gudmundsdottir, Vilmundur Gudnason, Mathias J. Gerl, Amber A. van der Heijden, Lori L. Jennings, Michael K. Hansen, Min Kim, Isabelle Leclerc, Christian Klose, Dmitry Kuznetsov, Dina Mansour Aly, Florence Mehl, Diana Marek, Olle Melander, Anne Niknejad, Filip Ottosson, Imre Pavo, Kevin Duffin, Samreen K. Syed, Janice L. Shaw, Over Cabrera, Timothy J. Pullen, Kai Simons, Michele Solimena, Tommi Suvitaival, Asger Wretlind, Peter Rossing, Valeriya Lyssenko, Cristina Legido Quigley, Leif Groop, Bernard Thorens, Paul W. Franks, Gareth E. Lim, Jennifer Estall, Mark Ibberson, Joline W. J. Beulens, Leen M't Hart, Ewan R. Pearson, Guy A. Rutter
Summary: We identified biomarkers for disease progression in type 2 diabetes cohorts, including metabolites, lipids, and proteins. Various substances such as homocitrulline, isoleucine, 2-aminoadipic acid, triacylglycerol species, and sphingomyelin 42:2;2 levels were found to predict faster progression towards insulin requirement. Proteins like GDF15/MIC-1, IL-18Ra, CRELD1, NogoR, FAS, and ENPP7 were associated with faster progression, while others like SMAC/DIABLO, SPOCK1, and HEMK2 predicted slower progression rates. The findings also suggested possible disease mechanisms and potential therapeutic avenues to slow diabetes progression.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Weiwei Xu, M. M. Fahd Qadir, Daniela Nasteska, Paula Mota de Sa, Caroline M. Gorvin, Manuel Blandino-Rosano, Charles R. Evans, Thuong Ho, Evgeniy Potapenko, Rajakrishnan Veluthakal, Fiona B. Ashford, Stavroula Bitsi, Jia Fan, Manika Bhondeley, Kejing Song, Venkata N. Sure, Siva S. V. P. Sakamuri, Lina Schiffer, Wandy Beatty, Rachael Wyatt, Daniel E. Frigo, Xiaowen Liu, Prasad V. Katakam, Wiebke Arlt, Jochen Buck, Lonny R. Levin, Tony Hu, Jay Kolls, Charles F. Burant, Alejandra Tomas, Matthew J. Merrins, Debbie C. Thurmond, Ernesto Bernal-Mizrachi, David J. Hodson, Franck Mauvais-Jarvis
Summary: Male mice without androgen receptor (AR) in pancreatic 0 cells have reduced insulin secretion and develop hyperglycemia. Testosterone activates an extranuclear AR, which enhances glucagon-like peptide-1 (GLP-1) insulin action. This study investigates the mechanisms through which testosterone enhances GLP-1-stimulated insulin secretion in male 0 cells, including the activation of cAMP production and the recruitment of Gas to GLP-1 receptor and AR complexes. Additionally, testosterone promotes insulin secretion in human islets through an actin remodeling cascade. The study provides insights into the genomic and non-genomic actions of AR in regulating insulin exocytosis.
Article
Endocrinology & Metabolism
M. V. Surekha, N. Suneetha, N. Balakrishna, Uday Kumar Putcha, K. Satyanarayana, J. J. Babu Geddam, Pagidoju Sreenu, B. Tulja, Raja Sriswan Mamidi, Guy A. Rutter, Gargi Meur
Summary: This study found that asymptomatic SARS-CoV-2 infection during pregnancy appears to be associated with various abnormal placental histopathologic changes related to placental hypoxia, independent of maternal anemia status. These findings support the independent role of SARS-CoV-2 in causing placental hypoxia in pregnant women.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Endocrinology & Metabolism
George Firth, Eleni Georgiadou, Alexander Griffiths, Maral Amrahli, Jana Kim, Zilin Yu, Ming Hu, Theodora J. Stewart, Isabelle Leclerc, Haruka Okamoto, Daniel Gomez, Philip J. Blower, Guy A. Rutter
Summary: Common variants in the SLC30A8 gene are associated with altered risk of type 2 diabetes, while rare loss-of-function variants in the gene are protective against the disease. This study found that the R138X mutation in the mouse SLC30A8 gene affects zinc and manganese homeostasis, leading to increased levels of these metals in pancreatic beta cells and improved insulin secretion.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Multidisciplinary Sciences
Stavroula Bitsi, Liliane El Eid, Yusman Manchanda, Affiong I. Oqua, Nimco Mohamed, Ben Hansen, Kinga Suba, Guy A. Rutter, Victoria Salem, Ben Jones, Alejandra Tomas
Summary: This study reveals the important role of GLP-1R in the treatment of type 2 diabetes, and the rapid desensitization of stimulated GLP-1Rs by beta-arrestins. By studying KO mice, it was found that they had weaker responses to GLP-1R agonists, but showed improvement 6 hours after agonist injection. This study unveils fundamental aspects of GLP-1R response regulation with direct application to the rational design of GLP-1R-targeting therapeutics.
Article
Cell Biology
Lina Sui, Qian Du, Anthony Romer, Qi Su, Pauline L. Chabosseau, Yurong Xin, Jinrang Kim, Sandra Kleiner, Guy A. Rutter, Dieter Egli
Summary: The rare SLC30A8 mutation is associated with a reduced risk for type 2 diabetes. The mutation does not affect the differentiation and function of beta cells, but results in a lack of crystalline zinc-containing insulin granules. The mutation enhances the protective role of zinc and increases resistance to apoptosis. These findings are important for understanding the protective role of zinc in type 2 diabetes.
Article
Medicine, Research & Experimental
Alice Adriaenssens, Johannes Broichhagen, Anne de Bray, Julia Ast, Annie Hasib, Ben Jones, Alejandra Tomas, Natalie Figueredo Burgos, Orla Woodward, Jo Lewis, Elisabeth O'Flaherty, Kimberley El, Canqi Cui, Norio Harada, Nobuya Inagaki, Jonathan Campbell, Daniel Brierley, David J. Hodson, Ricardo Samms, Fiona Gribble, Frank Reimann
Summary: The signaling pathways of the central glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) in the brain are not fully understood, and its role in GIP-based therapeutics for weight loss is critical. This study found that Gipr neurons in the hypothalamus and dorsal vagal complex (DVC) play a role in the control of energy balance, but they have different connectivity, transcriptomic profiles, and appetite-controlling mechanisms. The study also showed that GIPR agonists have restricted access to the central nervous system, primarily targeting circumventricular organs. These findings highlight the heterogeneity of the central GIPR signaling axis and suggest the need to consider multiple regulatory pathways in studying the effects of GIP pharmacology on feeding behavior.
Meeting Abstract
Endocrinology & Metabolism
S. J. Millership, V. Yu, F. Yong, A. Marta, K. Chen, E. Georgiadou, S. Bhattacharya, N. Parveen, S. Khadayate, Z. Stamoulis, Y. Ali, S. Dhawan, D. J. Withers, G. A. Rutter
Article
Medicine, Research & Experimental
Wing Yan So, Yilie Liao, Wai Nam Liu, Guy A. Rutter, Weiping Han
Summary: PAX6 plays a critical role in the survival of pancreatic beta cells and is down-regulated under diabetic conditions. Overexpression of PAX6 promotes beta cell survival and improves glycemic control after islet transplantation.
EMBO MOLECULAR MEDICINE
(2023)