Article
Cell Biology
Chien-Ting Wu, Keren Hilgendorf, Romina J. Bevacqua, Yan Hang, Janos Demeter, Seung K. Kim, Peter K. Jackson
Summary: Multiple G protein-coupled receptors (GPCRs) are localized to primary cilia in pancreatic islet cells, with FFAR4 and PTGER4 stimulating cAMP signaling and hormone secretion. The transport of GPCRs to cilia requires TULP3, which plays a key role in regulating hormone secretion by islet cells.
GENES & DEVELOPMENT
(2021)
Review
Pharmacology & Pharmacy
Patricio Atanes, Tanyel Ashik, Shanta J. Persaud
Summary: This study compared the expression of GPCR mRNA in human islets obtained from donors with normal weight range and those classified as obese. The altered expression of GPCRs in obesity may have an impact on islet function, and the study also considered the possible effects of adipokines on GPCRs showing altered expression in obesity.
PHARMACOLOGY & THERAPEUTICS
(2021)
Article
Biochemistry & Molecular Biology
Doreen Thor
Summary: This article discusses the expression profile of G protein-coupled receptors (GPCRs) and the impact of GPCR signaling on normal islet functionality.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2022)
Review
Endocrinology & Metabolism
Diego Balboa, Diepiriye G. Iworima, Timothy J. Kieffer
Summary: The review discusses the recent progress in generating and characterizing functional stem cell-derived beta cells, as well as the possibilities and challenges in diabetes disease modeling using stem cells.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Biochemical Research Methods
Emma L. Vanderlaan, Joshua Sexton, Carmella Evans-Molina, Adrian Buganza Tepole, Sherry L. Voytik-Harbin
Summary: This study presents a novel three-dimensional microphysiological system (MPS) that improves the health and function of pancreatic beta cells. By incorporating a polymerizable collagen scaffold, the MPS restores biophysical support and mechanobiological cues to the islets, leading to increased viability and function. Experimental results demonstrate the effectiveness of the MPS compared to traditional suspension culture formats.
Article
Medicine, Research & Experimental
Butian Wei, Xin Zhang, Jiwei Qian, Zhe Tang, Bo Zhang
Summary: Nrf2 is an important intracellular regulator of antioxidant stress, regulating not only antioxidant function but also insulin secretion, proliferation, and differentiation of beta cells, ER stress, and mitochondrial function. Pharmacological activation of Nrf2 has been shown to protect islet cells during different stages of transplantation in experiments.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Review
Chemistry, Multidisciplinary
Weikun Huang, Tongzhi Wu, Cong Xie, Christopher K. Rayner, Craig Priest, Heike Ebendorff-Heidepriem, Jiangbo (Tim) Zhao
Summary: The article discusses the importance of calcium ions in intra- and inter-cellular signaling, particularly in insulin secretion. Various sensors for detecting calcium ions are described, with a focus on emerging approaches and challenges in the field.
ADVANCED FUNCTIONAL MATERIALS
(2022)
Review
Multidisciplinary Sciences
Anneliese J. S. Flatt, Carla J. Greenbaum, James A. M. Shaw, Michael R. Rickels
Summary: Type 1 diabetes is characterized by loss and dysfunction of pancreatic islet beta cells, leading to insulin deficiency and hyperglycemia. Assessment of beta cell secretory capacity can detect the loss of beta cells during a presymptomatic phase of autoimmune attack. Islet transplantation can restore physiologic reserve capacity for insulin secretion.
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Fiona Louise Roberts, Luis Rodrigo Cataldo, Malin Fex
Summary: Recent studies have highlighted the important role of serotonin and melatonin as regulators of islet hormone secretion and glucose homeostasis. Dysregulated signaling of both amines is implicated in the development of type 2 diabetes mellitus. Serotonin plays a key role in islet cell physiology, while melatonin regulates circadian rhythm and nutrient metabolism.
TRENDS IN MOLECULAR MEDICINE
(2023)
Article
Endocrinology & Metabolism
Xinzhi Li, Ying Yang, Zheng Chen
Summary: This study reveals the essential role of YTHDC1 in maintaining beta-cell function and suggests that its downregulation in type 2 diabetes may be attributed to lipotoxicity and chronic inflammation.
METABOLISM-CLINICAL AND EXPERIMENTAL
(2023)
Article
Multidisciplinary Sciences
Martha Campbell-Thompson, Elizabeth A. Butterworth, J. Lucas Boatwright, Malavika A. Nair, Lith H. Nasif, Kamal Nasif, Andy Y. Revell, Alberto Riva, Clayton E. Mathews, Ivan C. Gerling, Desmond A. Schatz, Mark A. Atkinson
Summary: The dysregulation of glucagon secretion in type 1 diabetes involves the sympathetic nervous system and noradrenalin degradation pathways. The study found that sympathetic innervation at islets and intrinsic adrenergic signaling pathways could be novel targets for improving glucagon secretion in T1D patients.
SCIENTIFIC REPORTS
(2021)
Article
Medicine, Research & Experimental
Kailiang Zhang, Rong Bao, Fengyuan Huang, Kevin Yang, Yishu Ding, Lothar Lauterboeck, Masasuke Yoshida, Qinqiang Long, Qinglin Yang
Summary: Mitochondrial homeostasis plays a crucial role in the function of pancreatic beta-cells. The mitochondrial protein ATP synthase inhibitory factor subunit 1 (IF1) inhibits enzyme activity and may affect insulin granule maturation and mitochondrial mass within beta-cells. Knockdown of IF1 enhances glucose-induced insulin release, while overexpression of IF1 results in decreased insulin secretion. The study suggests that IF1 negatively regulates insulin production and secretion by inhibiting mitochondrial mass and respiration in beta-cells, highlighting its potential as a therapeutic target for diabetes.
LABORATORY INVESTIGATION
(2022)
Article
Endocrinology & Metabolism
David Cottet-Dumoulin, Quentin Perrier, Vanessa Lavallard, David Matthey-Doret, Laura Mar Fonseca, Juliette Bignard, Reine Hanna, Geraldine Parnaud, Fanny Lebreton, Kevin Bellofatto, Ekaterine Berishvili, Thierry Berney, Domenico Bosco
Summary: This study investigated the effect of intercellular contacts on the protein biosynthesis activity of alpha and beta cells. The results showed that intercellular contacts increased protein biosynthesis and insulin secretion in beta cells, but only increased insulin secretion at high glucose concentration. Heterogeneous contacts between alpha and beta cells had no impact on insulin secretion and protein biosynthesis in beta cells, but they increased glucagon secretion and decreased protein biosynthesis in alpha cells.
JOURNAL OF ENDOCRINOLOGY
(2023)
Article
Immunology
Burcak Yesildag, Joan Mir-Coll, Aparna Neelakandhan, Claire B. Gibson, Nikole R. Perdue, Chantal Rufer, Maria Karsai, Adelinn Biernath, Felix Forschler, Patricia Wu Jin, Patrick M. Misun, Alexandra Title, Andreas Hierlemann, Frederik F. Kreiner, Johnna D. Wesley, Matthias G. von Herrath
Summary: In this study, three in-vitro islet-immune injury models were established to investigate the immunopathogenesis of type 1 diabetes. The results showed that liraglutide protected pancreatic cells from immune attack.
CLINICAL IMMUNOLOGY
(2022)
Review
Endocrinology & Metabolism
Fanhua Wang, Mingyao Liu, Ning Wang, Jian Luo
Summary: This review discusses the role of G-protein coupled receptors (GPCRs) in osteoarthritis (OA), including the pathophysiological processes involved, preclinical and clinical trial data, and the challenges in developing therapies targeting GPCRs for OA.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Endocrinology & Metabolism
Louise Cottle, Wan Jun Gan, Ian Gilroy, Jaswinder S. Samra, Anthony J. Gill, Thomas Loudovaris, Helen E. Thomas, Wayne J. Hawthorne, Melkam A. Kebede, Peter Thorn
Summary: The study found that human pancreatic beta cells exhibit structural and functional polarity with respect to islet capillaries, in contrast to alpha cells; beta cells enrich presynaptic scaffold proteins when interacting with capillaries, indicating functional interactions; the same polarization of synaptic scaffold proteins was observed in islets from type 2 diabetic patients.
Article
Endocrinology & Metabolism
Marine L. Croze, Arthur Guillaume, Melanie Ethier, Grace Fergusson, Caroline Tremblay, Scott A. Campbell, Hasna Maachi, Julien Ghislain, Vincent Poitout
Summary: Activation of both GPR120 and GPR40 enhances insulin secretion in isolated islets, but combined deletion of these receptors has minimal effects on glucose homeostasis in vivo in mice.
Review
Endocrinology & Metabolism
Julien Ghislain, Vincent Poitout
Summary: This Review summarizes the physiological functions, pharmacology, and clinical studies of G protein-coupled receptors specific for lipid metabolite ligands and discusses the challenges associated with developing therapeutics for type 2 diabetes mellitus. Currently, therapeutic approaches targeting these receptors focus on increasing insulin secretion either by directly acting on beta-cells or indirectly on gastrointestinal enteroendocrine cells that release hormones regulating insulin secretion.
NATURE REVIEWS ENDOCRINOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Nicholas Norris, Belinda Yau, Melkam Alamerew Kebede
Summary: Insulin, essential for blood glucose stability, is produced by pancreatic beta-cells. Type 2 diabetes affects insulin secretion, resulting in dysfunctional production and secretion of ISGs. ISGs contain various proteins that can influence different stages of trafficking and secretion.
Article
Neurosciences
Caitlin Menzies, Shama Naz, David Patten, Thierry Alquier, Brian M. Bennett, Baptiste Lacoste
Summary: This study provides the first characterization and comparison of basal metabolism in three mouse models of NDDs, showing that each mouse model exhibits a unique metabolic signature that is sex-specific, independent of food consumption, and minimally influenced by physical activity. The findings highlight the importance of understanding NDD-associated metabolic alterations for future preclinical and clinical interventions.
Review
Biochemistry & Molecular Biology
Mark Germanos, Andy Gao, Matthew Taper, Belinda Yau, Melkam A. Kebede
Summary: The pancreatic beta-cell is responsible for producing and secreting insulin to regulate blood glucose levels, with the help of secretory granules (SGs) within the cell. Continuous generation of SGs by healthy beta-cells ensures sufficient insulin supply, while impaired biosynthesis of new insulin may contribute to beta-cell dysfunction in type 2 diabetes.
Review
Pharmacology & Pharmacy
Belinda Yau, Samantha Hocking, Sofianos Andrikopoulos, Melkam A. Kebede
Summary: It has been found that there are various populations of insulin secretory granules in pancreatic I3 cells, each with unique characteristics, highlighting the importance of targeting distinct ISG populations in anti-diabetic therapies.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Endocrinology & Metabolism
Nathalie Jouvet, Khalil Bouyakdan, Scott A. Campbell, Cindy Baldwin, Shannon E. Townsend, Maureen A. Gannon, Vincent Poitout, Thierry Alquier, Jennifer L. Estall
Summary: This study investigated genetic manipulation in beta-cells using an inducible tetracycline Off system, finding that expression of any tTA transgene in beta-cells significantly reduced insulin levels and secretion.
Editorial Material
Biochemistry & Molecular Biology
Belinda Yau, Melkam A. Kebede
Article
Multidisciplinary Sciences
Belinda Yau, Sheyda Naghiloo, Alexis Diaz-Vegas, Austin V. Carr, Julian Van Gerwen, Elise J. Needham, Dillon Jevon, Sing-Young Chen, Kyle L. Hoehn, Amanda E. Brandon, Laurence Macia, Gregory J. Cooney, Michael R. Shortreed, Lloyd M. Smith, Mark P. Keller, Peter Thorn, Mark Larance, David E. James, Sean J. Humphrey, Melkam A. Kebede
Summary: Pancreatic islets are crucial for maintaining blood glucose levels, with declining function being a characteristic of type 2 diabetes. A detailed proteomic analysis of mouse islets from various genetic or diet-induced models revealed that most proteins are expressed in all strains and diets, but with varying levels due to genetics. Islet mitochondrial function was identified as a major positive indicator of metabolic health across different strains.
Article
Endocrinology & Metabolism
Anne-Laure Castell, Alexis Vivoli, Trevor S. Tippetts, Isabelle Robillard Frayne, Zuraya Elisa Angeles, Valentine S. Moulle, Scott A. Campbell, Matthieu Ruiz, Julien Ghislain, Christine Des Rosiers, William L. Holland, Scott A. Summers, Vincent Poitout
Summary: This study found that oleate can induce the proliferation of pancreatic beta cells through the production of very-long-chain unsaturated sphingolipids in the presence of high glucose. Inhibiting key enzymes or proteins in the sphingolipid synthesis pathway can reduce the effect of oleate on beta cell proliferation.
Article
Endocrinology & Metabolism
Khalil Bouyakdan, Romane Manceau, Josephine L. Robb, Demetra Rodaros, Stephanie Fulton, Thierry Alquier
Summary: Astroglial ACBP has an important role in regulating energy balance and feeding. Deletion of ACBP in astrocytes can lead to hyperphagia and diet-induced obesity, while overexpression can reduce feeding and body weight. However, experiments show that deleting ACBP in astrocytes does not affect weight loss during transition from a high fat diet to a chow diet in obese mice, nor the metabolic parameters in mice fed with a normal chow diet. However, it does impair meal pattern and feeding responses during refeeding after a fast and during cold exposure. These findings challenge the previous view that astroglial ACBP has anorectic effects and suggest that the regulation of feeding by ACBP depends on metabolic status.
JOURNAL OF NEUROENDOCRINOLOGY
(2022)
Editorial Material
Endocrinology & Metabolism
James Cantley, Vincent Poitout, Rebecca L. Hull-Meichle
Summary: The year 2023 marks the 100th anniversary of the first report on glucagon, a hyperglycemic factor in pancreatic extracts. Glucagon has profound effects on metabolism and its dysregulation is a key feature of both major forms of diabetes. Understanding of glucagon production and its biological effects has lagged behind that of insulin, but recent research has led to significant developments. This collection of articles aims to capture the current understanding of glucagon and stimulate further research on this important hormone. Evaluating: 8/10.
JOURNAL OF ENDOCRINOLOGY
(2023)
Article
Cell & Tissue Engineering
Reena Singh, Louise Cottle, Thomas Loudovaris, Di Xiao, Pengyi Yang, Helen E. Thomas, Melkam A. Kebede, Peter Thorn
Summary: The differentiation of human stem cells into insulin-secreting beta-like cells has the potential to treat diabetes. The study focuses on the role of basement membrane proteins on the structure and function of human stem cell-derived beta cells, indicating that culturing differentiated beta cells on basement membrane proteins can enforce cell polarity and improve glucose-dependent insulin secretion.
STEM CELLS TRANSLATIONAL MEDICINE
(2021)
Article
Endocrinology & Metabolism
Christian H. Burns, Belinda Yau, Anjelica Rodriguez, Jenna Triplett, Drew Maslar, You Sun An, Reini E. N. van der Welle, Ross G. Kossina, Max R. Fisher, Gregory W. Strout, Peter O. Bayguinov, Tineke Veenendaal, David Chitayat, James A. J. Fitzpatrick, Judith Klumperman, Melkam A. Kebede, Cedric S. Asensio
Summary: VPS41 is essential for insulin granule biogenesis and regulated insulin secretion. Loss of VPS41 results in reduced insulin granule number, changes in transmembrane protein composition, and defects in granule-regulated exocytosis, ultimately leading to diabetes in mice.