Article
Nutrition & Dietetics
Wenqian Gu, Camilla Christine Bundgaard Anker, Christine Bodelund Christiansen, Tilo Moede, Per-Olof Berggren, Kjeld Hermansen, Soren Gregersen, Per Bendix Jeppesen
Summary: The study found that islet beta cells suppress glucagon secretion from alpha cells via direct cell-to-cell contact during co-culture, leading to a significant decrease in glucagon secretion from the alpha cells. However, this effect did not impact insulin secretion from beta cells, and the distribution of cells in co-culture differed from the in vivo arrangement of beta and alpha cells in mouse islets.
Article
Biochemistry & Molecular Biology
Reinaldo Sousa Dos Santos, Ignacio Babiloni-Chust, Laura Marroqui, Angel Nadal
Summary: Metabolism-disrupting chemicals (MDCs), including bisphenol-A (BPA) and tributyltin (TBT), can decrease the viability of alpha cells and negatively affect glucagon secretion. These effects are mediated through the activation of estrogen receptors and PPAR gamma. Other MDCs, such as perfluorooctanoic acid (PFOA), triphenylphosphate (TPP), triclosan (TCS), and dichlorodiphenyldichloroethylene (DDE), do not affect cell viability but still impair glucagon secretion. The study suggests that the alpha TC1-9 cell line can be used as a model to test metabolism-disrupting chemicals, and the proposed test methods could be incorporated into protocols for screening diabetogenic MDCs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Endocrinology & Metabolism
Arthur Ingersen, Malte Schmucker, Christina Alexandersen, Benjamin Graungaard, Tobias Thorngreen, Jacob Borch, Jens Juul Holst, Jorn Wulff Helge, Flemming Dela
Summary: The study aimed to investigate the interaction of semaglutide treatment and aerobic training on pancreatic β-cell secretory function in patients with type 2 diabetes. The results showed that aerobic training increased insulin secretion, and semaglutide treatment further improved β-cell secretory function. The combination of aerobic training and semaglutide treatment synergistically enhanced β-cell secretory function.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2023)
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
Multidisciplinary Sciences
Huixia Ren, Yanjun Li, Chengsheng Han, Yi Yu, Bowen Shi, Xiaohong Peng, Shufang Wu, Xiaojing Yang, Sneppen Kim, Liangyi Chen, Chao Tang, Tianming Zhang
Summary: The Ca2+ modulated pulsatile glucagon and insulin secretions by pancreatic alpha and beta cells play a crucial role in glucose homeostasis. However, the coordination between alpha and beta cells in producing different Ca2+ oscillation patterns is still unclear. This study used a microfluidic device and transgenic mice to record Ca2+ signals from islet alpha and beta cells and observed heterogeneous Ca2+ oscillation patterns intrinsic to each islet. The results showed that after glucose stimulation, the oscillations of alpha and beta cells were globally phase-locked, with a fixed time delay in the activation of alpha cells compared to beta cells and a tunable period in the activation of beta cells. The number of islet alpha cells was also found to be correlated with oscillation frequency. A mathematical model incorporating paracrine interactions was built and quantitatively agreed with the experimental data, highlighting the importance of cell-cell interaction in generating stable but tunable islet oscillation patterns.
NATURE COMMUNICATIONS
(2022)
Review
Endocrinology & Metabolism
Farzad Asadi, Savita Dhanvantari
Summary: This study focuses on the hyperglucagonemia in diabetic patients and the potential mechanisms of alpha cell dysfunction in pancreatic alpha cells, exploring how inhibition of glucagon secretion can be targeted for the treatment of diabetes mellitus.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Psychiatry
Despoina Aslanoglou, Suzanne Bertera, Marta Sanchez-Soto, R. Benjamin Free, Jeongkyung Lee, Wei Zong, Xiangning Xue, Shristi Shrestha, Marcela Brissova, Ryan W. Logan, Claes B. Wollheim, Massimo Trucco, Vijay K. Yechoor, David R. Sibley, Rita Bottino, Zachary Freyberg
Summary: DA and NE signaling in the pancreas regulate hormone release, potentially contributing to metabolic disturbances caused by APDs. DA acts as a biased agonist in the pancreas, modulating hormone release. Inhibiting DA receptors can increase hormone release, leading to metabolic disturbances.
TRANSLATIONAL PSYCHIATRY
(2021)
Article
Endocrinology & Metabolism
Nizar I. Mourad, Daela Xhema, Pierre Gianello
Summary: The study investigated the glucagon secretion characteristics of pig islet cells and found that high glucose concentration significantly inhibited glucagon secretion. In vivo experiments showed a quick decrease in plasma glucagon and a slower increase in plasma insulin after glucose injection.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Cell Biology
Erwin Ilegems, Galyna Bryzgalova, Jorge Correia, Burcak Yesildag, Edurne Berra, Jorge L. Ruas, Teresa S. Pereira, Per-Olof Berggren
Summary: This study found the presence of HIF-1 alpha in pancreatic cells during the progression of type 2 diabetes, and demonstrated that treatment with the HIF-1 alpha inhibitor PX-478 can improve beta cell function, prevent diabetes progression, and increase insulin secretion. The results showed that PX-478 treatment has an improving effect on mouse and human islets.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Norikiyo Honzawa, Kei Fujimoto, Masaki Kobayashi, Daisuke Kohno, Osamu Kikuchi, Hiromi Yokota-Hashimoto, Eri Wada, Yuichi Ikeuchi, Yoko Tabei, Gerald W. Dorn Ii, Kazunori Utsunomiya, Rimei Nishimura, Tadahiro Kitamura
Summary: Pkc delta plays a crucial role in glucagon secretion from pancreatic alpha-cells, and its depletion or inhibition leads to a decrease in glucagon secretion.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Endocrinology & Metabolism
Xiaona Cui, Jin Feng, Tianjiao Wei, Linxi Zhang, Shan Lang, Kun Yang, Jin Yang, Junling Liu, Michael Sterr, Heiko Lickert, Rui Wei, Tianpei Hong
Summary: This study found that glucagon receptor antagonism can improve blood glucose control and promote beta cell regeneration in mouse models of type 2 diabetes. It does so by increasing FGF21 levels, which affects the expression of genes related to beta cell identity, thereby increasing the number of beta cells and promoting their proliferation.
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)
Article
Cell Biology
Nour Zaimia, Joelle Obeid, Annie Varrault, Julia Sabatier, Christophe Broca, Patrick Gilon, Safia Costes, Gyslaine Bertrand, Magalie A. Ravier
Summary: Glucagon-like peptide 1 (GLP-1R) and glucose-dependent insulinotropic polypeptide (GIPR) receptors play important roles in glucose homeostasis. This study highlights the distinct roles of ARRB2 in regulating GLP-1R and GIPR signaling, as well as the potential consequences of its decreased expression in pathological conditions such as diabetes.
Editorial Material
Endocrinology & Metabolism
Jonathan Weitz, Danusa Menegaz, Alejandro Caicedo
Summary: Pancreatic islets rely on intricate cell-cell communication mechanisms for proper function. Studies have shown that hormone secretion from endocrine cell types is diminished when cells are dispersed, but reestablishing cellular contacts can restore hormone secretory function. Recent advances in understanding islet cell cross talk and communication networks may guide efforts to restore islet function in diabetes.
Article
Multidisciplinary Sciences
Daisuke Saito, Yuko Nakagawa, Takashi Sato, Ayako Fukunaka, Ofejiro Blessing Pereye, Nobuhiro Maruyama, Hirotaka Watada, Yoshio Fujitani
Summary: In this study, we developed a method to specifically detect and measure the secretion of pancreatic polypeptide (PP), and investigated the molecular mechanisms that regulate PP secretion. We found that the secretion of PP is triggered by an increase in intracellular calcium concentrations via voltage-dependent calcium channels, unlike the mechanism of insulin secretion.
Article
Geriatrics & Gerontology
Eva Tuduri, Sergi Soriano, Lucia Almagro, Anabel Garcia-Heredia, Alex Rafacho, Paloma Alonso-Magdalena, Angel Nadal, Ivan Quesada
Summary: Aging is associated with decreased beta-cell adaptations and insulin sensitivity. Aged mice with low insulin sensitivity demonstrate worsened glucose metabolism and impaired insulin secretion, possibly due to compromised mitochondrial function.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2022)
Article
Environmental Sciences
Ignacio Babiloni-Chust, Reinaldo S. dos Santos, Regla M. Medina-Gali, Atenea A. Perez-Serna, Jose-Antonio Encinar, Juan Martinez-Pinna, Jan-Ake Gustafsson, Laura Marroqui, Angel Nadal
Summary: 17 beta-estradiol protects pancreatic beta-cells from apoptosis via estrogen receptors ER alpha, ER beta, and GPER. Conversely, the endocrine disruptor bisphenol-A (BPA) increases basal apoptosis in the same cell type through the same estrogen receptors. The molecular events that trigger these opposite actions have not been identified yet.
ENVIRONMENT INTERNATIONAL
(2022)
Article
Biochemistry & Molecular Biology
Reinaldo Sousa Dos Santos, Regla Maria Medina-Gali, Ignacio Babiloni-Chust, Laura Marroqui, Angel Nadal
Summary: Identification tests for Metabolism Disrupting Chemicals (MDCs) with diabetogenic activity are necessary. This study used various cell lines to assess the effects of endocrine disruptors on cell viability and glucose-stimulated insulin secretion (GSIS). Results suggest that one chemical could be a new diabetogenic agent, and the EndoC-beta H1 cell line is a suitable human beta-cell model for testing diabetogenic MDCs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Ruba Al-Abdulla, Hilda Ferrero, Sergi Soriano, Talia Boronat-Belda, Paloma Alonso-Magdalena
Summary: Endocrine-disrupting chemicals (EDCs) are chemical substances that can interfere with the normal function of the endocrine system. Among them, metabolism-disrupting chemicals (MDCs) can promote metabolic changes and lead to metabolic disorders. This study evaluated the effects of seven well-known EDCs on pancreatic beta-cell function and found that most of the tested chemicals had deleterious effects. The results provide molecular information on the direct effects of these chemicals and suggest that the experimental systems used in this study can be effective tools for studying MDC effects on pancreatic beta-cell physiology.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Kevin Bernal, Charbel Touma, Chedi Erradhouani, Talia Boronat-Belda, Lucas Gaillard, Sara Al Kassir, Helene Le Mentec, Corinne Martin-Chouly, Normand Podechard, Dominique Lagadic-Gossmann, Sophie Langouet, Francois Brion, Anja Knoll-Gellida, Patrick J. Babin, Iva Sovadinova, Pavel Babica, Karine Andreau, Robert Barouki, Jan Vondracek, Paloma Alonso-Magdalena, Etienne Blanc, Min Ji Kim, Xavier Coumoul
Summary: The prevalence of metabolic diseases is increasing and there is evidence to suggest that the chemical environment plays a role in their pathogenesis. This review explores the biological processes involved in the development of metabolic diseases and proposes an integrated pathophysiological viewpoint. The need to improve testing and assessment of endocrine disruptors to prevent and manage metabolic diseases is also discussed.
Review
Cell Biology
Eva Tuduri, Sergi Soriano, Lucia Almagro, Eduard Montanya, Paloma Alonso-Magdalena, Angel Nadal, Ivan Quesada
Summary: This review summarizes the age-related alterations, adaptations, and failures of pancreatic β-cells at the molecular, morphological, and functional levels in both mice and humans. The findings suggest that changes in β-cell proliferation, apoptosis, and function with age may impact the development of type 2 diabetes.
AGEING RESEARCH REVIEWS
(2022)
Article
Biochemistry & Molecular Biology
Reinaldo Sousa Dos Santos, Ignacio Babiloni-Chust, Laura Marroqui, Angel Nadal
Summary: Metabolism-disrupting chemicals (MDCs), including bisphenol-A (BPA) and tributyltin (TBT), can decrease the viability of alpha cells and negatively affect glucagon secretion. These effects are mediated through the activation of estrogen receptors and PPAR gamma. Other MDCs, such as perfluorooctanoic acid (PFOA), triphenylphosphate (TPP), triclosan (TCS), and dichlorodiphenyldichloroethylene (DDE), do not affect cell viability but still impair glucagon secretion. The study suggests that the alpha TC1-9 cell line can be used as a model to test metabolism-disrupting chemicals, and the proposed test methods could be incorporated into protocols for screening diabetogenic MDCs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Endocrinology & Metabolism
Juan Martinez-Pinna, Roberto Sempere-Navarro, Regla M. Medina-Gali, Esther Fuentes, Ivan Quesada, Robert M. Sargis, Leonardo Trasande, Angel Nadal
Summary: Plastic pollution threatens wildlife and humans through physical and chemical effects. The release of endocrine disrupting chemicals (EDCs) from plastics, such as bisphenols and phthalates, has consequences on human health, particularly on glucose regulation. Epidemiological, animal, and cellular studies have linked exposure to these EDCs to altered glucose regulation and diabetes mellitus, with a focus on the role of pancreatic I3-cells. The data indicate that these EDCs disrupt insulin sensitivity, glucose tolerance, and other processes involved in glucose homeostasis, highlighting the importance of reducing plastic pollution and human exposure to EDCs.
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
(2023)
Article
Endocrinology & Metabolism
Alba Sanz-Gonzalez, Irene Cozar-Castellano, Christophe Broca, Julia Sabatier, Gerardo A. Acosta, Miriam Royo, Carla Hernando-Munoz, Tomas Torroba, German Perdomo, Beatriz Merino
Summary: This study investigated the use of synthetic preimplantation factor (sPIF) as a potential therapeutic tool for improving glucose-stimulated insulin secretion, glucose tolerance, and insulin sensitivity in diabetes. The results showed that sPIF significantly increased insulin secretion in human islets. Furthermore, continuous administration of sPIF improved circulating insulin levels and glucose tolerance in a preclinical murine model of type 2 diabetes.
DIABETES OBESITY & METABOLISM
(2023)
Article
Biochemistry & Molecular Biology
Ruba Al-Abdulla, Hilda Ferrero, Talia Boronat-Belda, Sergi Soriano, Ivan Quesada, Paloma Alonso-Magdalena
Summary: Humans are exposed to environmental pollutants, some of which can disrupt metabolism and lead to metabolic disorders. These metabolism-disrupting chemicals (MDCs) are found in consumer products and can affect pancreatic alpha-cells. In this study, seven major toxic classes of MDCs were investigated and found to cause functional alterations in pancreatic alpha-cells, impacting glucagon secretion and gene expression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Correction
Endocrinology & Metabolism
Beatriz Merino, Elena Casanueva-Alvarez, Ivan Quesada, Carlos M. Gonzalez-Casimiro, Cristina M. Fernandez-Diaz, Tamara Postigo-Casado, Malcolm A. Leissring, Klaus H. Kaestner, German Perdomo, Irene Cozar-Castellano