Article
Multidisciplinary Sciences
Ana I. Fernandez-Marino, Xiao-Feng Tan, Chanhyung Bae, Kate Huffer, Jiansen Jiang, Kenton J. Swartz
Summary: The study reveals the structure and functional mechanisms of the Kv2.1 voltage-activated potassium channel, providing insights into how mutations affect channel activity. Inactivation in Kv2.1 is found to be caused by dynamic alterations in electromechanical coupling, which suggests a conserved mechanism in voltage-activated cation channels and its relevance for regulating neuron firing.
Article
Multidisciplinary Sciences
Jessica R. Chaffey, Jay Young, Kaiyven A. Leslie, Katie Partridge, Pouria Akhbari, Shalinee Dhayal, Jessica L. Hill, Kyle C. A. Wedgwood, Edward Burnett, Mark A. Russell, Sarah J. Richardson, Noel G. Morgan
Summary: The study aimed to investigate the factors influencing chronic enteroviral infection using a 1.1B4 beta cell line.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Mark L. Dallas, Moza M. Al-Owais, Nishani T. Hettiarachchi, Matthew Scott Vandiver, Heledd H. Jarosz-Griffiths, Jason L. Scragg, John P. Boyle, Derek Steele, Chris Peers
Summary: Studies have shown that H2S inhibits Kv2.1 channels through S-sulfhydration mechanism, and enhances neuronal excitability. These results highlight an important role for H2S in shaping cellular excitability through S-sulfhydration of Kv2.1 in the central nervous system.
SCIENTIFIC REPORTS
(2021)
Article
Biophysics
Rebecka J. Sepela, Robert G. Stewart, Luis A. Valencia, Parashar Thapa, Zeming Wang, Bruce E. Cohen, Jon T. Sack
Summary: In this study, we found that AMIGO1 modulates the conductance activation pathway of Kv2.1 channels. AMIGO1 accelerates the movement of voltage sensors and shifts the gating charge-voltage relationship. When voltage sensors are detained by toxins, AMIGO1 has a greater impact on the conductance-voltage relationship. AMIGO1 destabilizes the earliest resting state of the voltage sensors.
BIOPHYSICAL JOURNAL
(2022)
Article
Endocrinology & Metabolism
Tamadher A. Alghamdi, Nicole A. J. Krentz, Nancy Smith, Aliya F. Spigelman, Varsha Rajesh, Alokkumar Jha, Mourad Ferdaoussi, Kunimasa Suzuki, Jing Yang, Jocelyn E. Manning Fox, Han Sun, Zijie Sun, Anna L. Gloyn, Patrick E. MacDonald
Summary: The Zmiz1 gene in beta cells is essential for maintaining normal glucose homeostasis. Genetic variations at the ZMIZ1 locus may affect the risk of type 2 diabetes by reducing the expansion of beta cell mass and the ability to maintain a mature beta cell state under metabolic stress.
MOLECULAR METABOLISM
(2022)
Article
Endocrinology & Metabolism
Eike Frueh, Christin Elgert, Frank Eggert, Stephan Scherneck, Ingo Rustenbeck
Summary: The study investigated the role of depolarization in the inverse glucose-dependence of glucagon secretion by comparing the effects of K-ATP channel block and high potassium. Results showed that lowering glucose could increase glucagon secretion before decreasing insulin secretion, indicating alpha cell-intrinsic signal recognition. Additionally, depolarization had different effects on insulin and glucagon secretion, suggesting that K-ATP channel closure in alpha cells is less readily achieved than in beta cells.
Article
Endocrinology & Metabolism
Bilal Singh, Firas Khattab, Patrick Gilon
Summary: The study reveals that glucose controls alpha-cell [Ca2+](c) and glucagon secretion through multiple mechanisms. Increasing glucose concentration modestly decreases [Ca2+](c) in alpha-cells independently of their K-ATP channels and partly via somatostatin (SST). The changes in [Ca2+](c) parallel changes in glucagon release. Glucose also attenuates the efficacy of Ca2+ on exocytosis.
MOLECULAR METABOLISM
(2022)
Article
Multidisciplinary Sciences
Nicholas C. Vierra, Samantha C. O'Dwyer, Collin Matsumoto, L. Fernando Santana, James S. Trimmer
Summary: In mammalian brain neurons, membrane depolarization triggers Ca2+ influx through voltage-gated Ca2+ channels, leading to diverse cellular responses, including gene expression. The L-type Ca2+ channels in neuronal soma and dendrites play a key role in this process. The organization of signaling complexes by Kv2.1 at endoplasmic reticulum-plasma membrane junctions enhances the clustering and activity of Cav1.2 channels, impacting somatic Ca2+ signals and excitation-transcription coupling.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Pharmacology & Pharmacy
Hongliang Li, Wenwen Zhuang, Mi Seon Seo, Jin Ryeol An, Yongqi Yang, Yiwen Zha, Jingyan Liang, Zheng-xin Xu, Won Sun Park
Summary: Lorcainide inhibits vascular Kv channels by changing the channels' voltage sensors and affecting their inactivation gating properties, leading to altered channel activity, inactivation speed, and use (state)-dependent inhibition. The concentration-dependent and use-dependent inhibition of Kv channels by lorcainide was observed in this study.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Physiology
Satomi Kamata, Maki Kimura, Sadao Ohyama, Shuichiro Yamashita, Yoshiyuki Shibukawa
Summary: Cementum, secreted by cementoblasts, provides attachment for collagen fibers connecting teeth to alveolar bone. The study investigated the biophysical and pharmacological properties of ion channels expressed in human cementoblast (HCEM) cell lines, revealing the presence of TEA- and IbTX-sensitive large-conductance Ca2+-activated K+ channels and voltage-dependent Na+ channels in HCEM cells.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Multidisciplinary Sciences
Hongbo Chen, Jiahua Deng, Qiang Cui, Baron Chanda, Katherine Henzler-Wildman
Summary: By combining experimental results with molecular dynamics simulations, this study reveals that the engineered temperature-sensitive variant of the Shaker potassium channel has the same overall secondary structure as the wild-type channel, but exhibits local changes in backbone torsion angles near the substitution sites (V369S and F370S). Notably, these structural differences lead to increased hydration of specific regions in the temperature-sensitive variant at higher temperatures, highlighting the impact of subtle differences in primary structure on solvation and temperature-dependent activity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Endocrinology & Metabolism
Eun Young Lee, Jing W. Hughes
Summary: Primary cilia are important organelles on the surfaces of most eukaryotic cells that play a role in development and signaling pathways. Dysfunction of cilia is associated with human developmental and genetic disorders, including obesity and diabetes. This article reviews the expression and function of cilia in pancreatic islet cells and discusses the role of cilia in glucose homeostasis and human diseases.
DIABETES & METABOLISM JOURNAL
(2023)
Review
Biochemistry & Molecular Biology
Ronit Vogt Sionov, Ronit Ahdut-HaCohen
Summary: Type 1 diabetes is a chronic autoimmune disease characterized by the destruction of insulin-producing beta-cells, leading to impaired glucose homeostasis. Mesenchymal stem cells (MSCs) have been found to support pancreatic islet function and protect islets through various mechanisms, including angiogenesis, immune response suppression, and secretion of growth factors.
Article
Cell Biology
Kristina Haer, Natalia N. Lysenko, Daniela Dimitrova, Torsten Schlueter, Olga Zavaritskaya, Andrej G. Kamkin, Mitko Mladenov, Olaf Grisk, Ralf Koehler, Hristo Gagov, Rudolf Schubert
Summary: Vascular smooth muscle Kv2 channels contribute to myogenic autoregulation by fine-tuning the myogenic response. Specifically, Kv2.1 channels are predominantly expressed in smooth muscle cells and provide a negative feedback mechanism by preventing vasomotion and safeguarding the myogenic response. The Kv2 channel inhibitor stromatoxin induces vasomotion in some vessels, leading to disturbances in the myogenic response.
Review
Biochemistry & Molecular Biology
Valerij S. Sokolov, Vladimir V. Cherny, Artem G. Ayuyan, Thomas E. DeCoursey
Summary: H(V)1 channels, resembling the voltage-sensing domain of other voltage-gated ion channels, feature a unique Delta pH dependent gating mechanism that regulates channel opening by pH on both sides of the membrane. Two mechanisms, the countercharge mechanism and the electrostatic mechanism, are proposed to contribute to this Delta pH dependent gating. Both mechanisms are likely to operate together to regulate the gating of H(V)1 channels.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
(2021)
Review
Endocrinology & Metabolism
Richard Yan-Do, Patrick E. MacDonald
Article
Endocrinology & Metabolism
Patrick E. MacDonald
Review
Cell Biology
Victoria L. Tokarz, Patrick E. MacDonald, Amira Klip
JOURNAL OF CELL BIOLOGY
(2018)
Article
Genetics & Heredity
Soren K. Thomsen, Anne Raimondo, Benoit Hastoy, Shahana Sengupta, Xiao-Qing Dai, Austin Bautista, Jenny Censin, Anthony J. Payne, Mahesh M. Umapathysivam, Aliya F. Spigelman, Amy Barrett, Christopher J. Groves, Nicola L. Beer, Jocelyn E. Manning Fox, Mark I. McCarthy, Anne Clark, Anubha Mahajan, Patrik Rorsman, Patrick E. MacDonald, Anna L. Gloyn
Review
Endocrinology & Metabolism
Rafael e Drigo, Birbickram Roy, Patrick E. MacDonald
Article
Multidisciplinary Sciences
Sos Skovso, Evgeniy Panzhinskiy, Jelena Kolic, Haoning Howard Cen, Derek A. Dionne, Xiao-Qing Dai, Rohit B. Sharma, Lynda Elghazi, Cara E. Ellis, Katharine Faulkner, Stephanie A. M. Marcil, Peter Overby, Nilou Noursadeghi, Daria Hutchinson, Xiaoke Hu, Hong Li, Honey Modi, Jennifer S. Wildi, J. Diego Botezelli, Hye Lim Noh, Sujin Suk, Brian Gablaski, Austin Bautista, Ryekjang Kim, Corentin Cras-Meneur, Stephane Flibotte, Sunita Sinha, Dan S. Luciani, Corey Nislow, Elizabeth J. Rideout, Eric N. Cytrynbaum, Jason K. Kim, Ernesto Bernal-Mizrachi, Laura C. Alonso, Patrick E. MacDonald, James D. Johnson
Summary: Insulin receptor protein is present in pancreatic beta-cells, but the consequences of beta-cell insulin resistance are incompletely understood. Here the authors use a combination of mouse studies and mathematical modelling to show that loss of beta-cell insulin receptor affects male and female mice differently and can contribute to hyperinsulinemia in the context of glucose stimulation.
NATURE COMMUNICATIONS
(2022)
Article
Endocrinology & Metabolism
Marko Gosak, Richard Yan-Do, Haopeng Lin, Patrick E. MacDonald, Andraz Stozer
Summary: Pancreatic islets show synchronized calcium oscillations and waves, which are glucose-dependent. Higher glucose levels enhance the activity and proportion of global calcium waves in the islets, leading to denser and less fragmented functional networks. Hub regions play important roles in stimulatory conditions and the roles of initiators and hubs do not overlap. In type 2 diabetes, the islets show reduced activity, locally restricted waves, and more segregated networks.
Article
Biochemistry & Molecular Biology
Carolin Hoefner, Tenna Holgersen Bryde, Celina Pihl, Sylvia Naiga Tiedemann, Sophie Emilie Bresson, Hajira Ahmed Hotiana, Muhammad Saad Khilji, Theodore Dos Santos, Michele Puglia, Paola Pisano, Mariola Majewska, Julia Durzynska, Kristian Klindt, Justyna Klusek, Marcelo J. Perone, Robert Bucki, Per Marten Hagglund, Pontus Emanuel Gourdon, Kamil Gotfryd, Edyta Urbaniak, Malgorzata Borowiak, Michael Wierer, Patrick Edward MacDonald, Thomas Mandrup-Poulsen, Michal Tomasz Marzec
Summary: Apart from known functions, such as chaperoning and disulfide bond formation, the complete molecular sequence of proinsulin folding remains unclear. In this study, we investigated the role of FKBP2, an ER-resident proline isomerase, in proinsulin folding. Through experiments and analysis, we found that FKBP2 depletion resulted in misfolding of proinsulin and increased apoptosis in pancreatic beta-cells. Additionally, we observed an overexpression of FKBP2 mRNA in beta-cells from pancreatic islets of type 2 diabetes patients. These findings suggest that FKBP2 plays a crucial role in the correct folding of proinsulin.
Article
Physiology
Mourad Ferdaoussi, Nancy Smith, Haopeng Lin, Austin Bautista, Aliya F. Spigelman, James Lyon, XiaoQing Dai, Jocelyn E. Manning Fox, Patrick E. MacDonald
PHYSIOLOGICAL REPORTS
(2020)
Article
Physiology
Shara Khan, Mourad Ferdaoussi, Austin Bautista, Valerie Bergeron, Nancy Smith, Vincent Poitout, Patrick E. MacDonald
PHYSIOLOGICAL REPORTS
(2019)
Article
Medicine, Research & Experimental
Megan E. Capozzi, Berit Svendsen, Sara E. Encisco, Sophie L. Lewandowski, Mackenzie D. Martin, Haopeng Lin, Justin L. Jaffe, Reilly W. Coch, Jonathan M. Haldeman, Patrick E. MacDonald, Matthew J. Merrins, David A. D'Alessio, Jonathan E. Campbell
Article
Medicine, Research & Experimental
Nathaniel J. Hart, Radhika Aramandla, Gregory Poffenberger, Cody Fayolle, Ariel H. Thames, Austin Bautista, Aliya F. Spigelman, Jenny Aurielle B. Babon, Megan E. DeNicola, Prasanna K. Dadi, William S. Bush, Appakalai N. Balamurugan, Marcela Brissova, Chunhua Dai, Nripesh Prasad, Rita Bottino, David A. Jacobson, Mitchell L. Drumm, Sally C. Kent, Patrick E. MacDonald, Alvin C. Powers
Article
Endocrinology & Metabolism
Jianyang Fu, Xiaoqing Dai, Gregory Plummer, Kunimasa Suzuki, Austin Bautista, John M. Githaka, Laura Senior, Mette Jensen, Dafna Greitzer-Antes, Jocelyn E. Manning Fox, Herbert Y. Gaisano, Christopher B. Newgard, Nicolas Touret, Patrick E. MacDonald
Article
Endocrinology & Metabolism
Hannah M. Gordon, Neil Majithia, Patrick E. MacDonald, Jocelyn E. Manning Fox, Poonam R. Sharma, Frances L. Byrne, Kyle L. Hoehn, Carmella Evans-Molina, Linda Langman, Kenneth L. Brayman, Craig S. Nunemaker
Article
Cell Biology
Michaela Aichler, Daniela Borgmann, Jan Krumsiek, Achim Buck, Patrick E. MacDonald, Jocelyn E. Manning Fox, James Lyon, Peter E. Light, Susanne Keipert, Martin Jastroch, Annette Feuchtinger, Nikola S. Mueller, Na Sun, Andrew Palmer, Theodore Alexandrov, Martin Hrabe de Angelis, Susanne Neschen, Matthias H. Tschop, Axel Walch