Review
Endocrinology & Metabolism
Marle Pretorius, Carol Huang
Summary: During pregnancy, the mother develops insulin resistance to prioritize nutrients for the fetus, leading to changes in insulin secretion and calcium dynamics in the maternal islets of Langerhans. These changes help maintain glucose homeostasis and prevent gestational diabetes.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Endocrinology & Metabolism
Karina Rodrigues-dos-Santos, Gitanjali Roy, Derk D. Binns, Magdalena G. Grzemska, Luiz F. Barella, Fiona Armoo, Melissa K. McCoy, Andy Huynh, Jonathan Z. Yang, Bruce A. Posner, Melanie H. Cobb, Michael A. Kalwat
Summary: The small molecule SW016789 has time-dependent effects on endoplasmic reticulum (ER) stress and function in pancreatic islet beta cells. Acute treatment enhances insulin secretion, while chronic exposure transiently induces ER stress and inhibits secretory function in a reversible manner. SW016789 acts upstream of voltage-dependent calcium channels and potentiates nutrient-induced calcium influx.
Review
Biology
Hidekatsu Yanai, Hiroki Adachi, Mariko Hakoshima, Hisayuki Katsuyama
Summary: Mitochondria are organelles that generate adenosine triphosphate through aerobic respiration. Imeglimin is a novel oral hypoglycemic agent that targets mitochondrial function and reduces reactive oxygen species production. It improves glucose metabolism, preserves pancreatic beta-cell mass, inhibits hepatic glucose production, and improves insulin sensitivity. Imeglimin also improves vascular dysfunction and reduces ischemia-induced brain damage. It can be a useful therapeutic option for diabetic complications in type 2 diabetic patients.
Review
Chemistry, Multidisciplinary
Chun-cao Xu, Yi-fan Lin, Mu-yang Huang, Xiao-lei Zhang, Pei Wang, Ming-qing Huang, Jin-jian Lu
Summary: Inducing cell death is a potential strategy for cancer therapy due to the sustained proliferative potential of cancer cells. Paraptosis, characterized by endoplasmic reticulum and/or mitochondrial swelling and cytoplasmic vacuolization, is a less investigated mode of cell death. Evidence shows that paraptosis can be triggered by various chemical compounds, particularly in cancer cells, suggesting its potential application in cancer therapy. However, there are significant gaps in our understanding of the role of paraptosis in cancer.
ACTA PHARMACOLOGICA SINICA
(2023)
Article
Biochemistry & Molecular Biology
Piper A. Robida, Alena P. Chumanevich, Alexa Orr Gandy, John W. Fuseler, Prakash Nagarkatti, Mitzi Nagarkatti, Carole A. Oskeritzian
Summary: The study suggests that in the pre-lesional phase of atopic dermatitis, elevated levels of ceramides lead to increased apoptosis of skin cells, which may be influenced by activated mast cells. The results reveal that the MC/Cer axis may be an essential pathogenic feature in the development of atopic dermatitis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Andrei I. Smid, Sam J. Garforth, Maryam S. Obaid, Hannah R. Bollons, John R. James
Summary: The study reconstitutes pre-T cell receptor (preTCR) expression in non-immune cells and shows that signaling is not required for its rapid internalization and degradation observed during T-cell development. The preTCR can drive tonic signaling in T cells and sustain cell surface expression even in the absence of ligand binding. These findings provide insight into the unique features of the preTCR and its role in TCR lineage commitment.
JOURNAL OF CELL BIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Mohamed Mahameed, Shuai Xue, Bozhidar-Adrian Stefanov, Ghislaine Charpin-El Hamri, Martin Fussenegger
Summary: In this study, a rapamycin-actuated protein-induction device (RAPID) based on split sec-TEVp was engineered to achieve rapid insulin release. This technology may serve as a foundation for cell-based therapies requiring instantaneous biopharmaceutical availability.
Article
Multidisciplinary Sciences
Emanuele Bosi, Piero Marchetti, Guy Allen Rutter, Decio Laks Eizirik
Summary: By analyzing single-cell RNASeq data from T1D and T2D patients and controls, this study found that while there were conserved changes in alpha cell identity gene expression, there were distinct alterations in glucagon secretion pathways in T1D and T2D patients, possibly due to immune- or metabolism-mediated stress events.
Review
Endocrinology & Metabolism
Michael A. Kalwat, Donalyn Scheuner, Karina Rodrigues-Dos-Santos, Decio L. Eizirik, Melanie H. Cobb
Summary: Pancreatic beta cells play a crucial role in maintaining glucose homeostasis by producing insulin and adapting to increased secretion demands. The unfolded protein response of the endoplasmic reticulum is a key mechanism used by beta cells to cope with the demands for insulin production. Failure of compensatory mechanisms may contribute to the development of diabetes.
Review
Endocrinology & Metabolism
Michael A. Kalwat, Donalyn Scheuner, Karina Rodrigues-Dos-Santos, Decio L. Eizirik, Melanie H. Cobb
Summary: Pancreatic beta cells dedicate much of their protein translation capacity to producing insulin and have mechanisms to increase insulin production capability even in the face of peripheral insulin resistance. They utilize the unfolded protein response of the endoplasmic reticulum to adapt to changing demands for insulin production, and failure of these mechanisms can contribute to diabetes. Resting beta cells by reducing endogenous insulin demand shows promise as a therapeutic strategy.
Article
Endocrinology & Metabolism
Maroof Alam, Anoop Arunagiri, Leena Haataja, Mauricio Torres, Dennis Larkin, John Kappler, Niyun Jin, Peter Arvan
Summary: This study demonstrates that mice carrying the proinsulin-R(B22)E heterozygous mutation do not develop diabetes at any age, but show subtle signs of proinsulin misfolding in isolated islets. Males with the mutation exhibit glucose intolerance and develop diabetes after exposure to a high-fat diet. The severity of diabetes is greater in homozygotes, and disease development is associated with beta-cell heterogeneity and increased proinsulin-rich/insulin-poor cells.
Article
Chemistry, Physical
Rui Gu, Wanlan Yang, Lifei Han, Chao Liu, Yatao Xu, Yunlong Liu, Weili Si, Wenjun Wang, Xiaochen Dong
Summary: A tumor microenvironment and photo-responsive CO nanoplatform Ca-Flav nanoparticles were developed, which could release CO in both normoxia and hypoxia conditions upon irradiation at tumor lesion. In vitro experiments demonstrated that CO could activate endoplasmic reticulum stress-related signal pathways, resulting in mitochondrial dysfunction and cell apoptosis. The Ca-Flav NPs showed excellent biocompatibility and tumor inhibition effect in vivo, providing new insight into CO as a potential treatment.
Article
Chemistry, Applied
Shane M. Hickey, Ian R. D. Johnson, Elena Dallerba, Mark J. Hackett, Massimiliano Massi, Joanna Lazniewska, Lauren A. Thurgood, Frederick M. Pfeffer, Douglas A. Brooks, Trent D. Ashton
Summary: We introduce a highly fluorescent, solvatochromic, 1,8-naphthalimide probe that enables the simultaneous imaging of lipid droplets and endoplasmic reticulum, with distinguishable emission maxima. By delineating organelles based on their emission profiles, we are able to visualize lipid droplet biogenesis and intercellular trafficking events. Furthermore, this probe demonstrates potential histochemical applications by staining myelin lipids in ex vivo brain tissue.
Article
Chemistry, Multidisciplinary
Xue Li, Mingming Zhen, Chen Zhou, Meilan Yu, Lei Liu, Chunying Shu, Chunru Wang
Summary: This study investigates the use of hydroxylated [70] fullerene nanoparticles (HFNPs) as antioxidants to reverse insulin resistance in diabetes. The study shows that HFNPs can alleviate insulin resistance by regulating oxidative stress and endoplasmic reticulum stress, resulting in improved glucose uptake and reduced blood glucose levels. Furthermore, HFNPs inhibit the activation of phosphorylated c-Jun N-terminal kinase (JNK), reactivating the insulin receptor substrate (IRS) signaling pathway and inhibiting gluconeogenesis. Importantly, HFNPs exhibit no severe toxicity to main tissues. This research contributes to the understanding of the role of antioxidants in regulating insulin resistance and provides new perspectives for the treatment of insulin resistance-related diseases.
Review
Biochemistry & Molecular Biology
Ji-Hye Lee, Jaemin Lee
Summary: Increased life span and nutritional affluency have resulted in a rise in age-related diseases, such as obesity and type 2 diabetes, which impose significant burdens on society. Dysfunction of pancreatic beta-cells, responsible for glucose control, plays a crucial role in both type 1 and type 2 diabetes. Recent studies have linked cellular senescence to cellular stresses, including ER stress, and have shown that beta-cell senescence contributes to dysfunction and impaired glucose homeostasis. This review discusses the current understanding of cellular senescence, beta-cell function, ER stress, and its impact on beta-cell senescence and dysfunction.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cardiac & Cardiovascular Systems
Daniel H. Enter, Anthony Zaki, Brett F. Duncan, Jane Kruse, Adin-Cristian Andrei, Zhi Li, S. Chris Malaisrie, Sanjiv J. Shah, James D. Thomas, Patrick M. McCarthy
JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
(2016)
Article
Pharmacology & Pharmacy
Daniel H. Enter, Anthony L. Zaki, Megan Marsh, Nikki Cool, Jane Kruse, Zhi Li, Adin-Cristian Andrei, Adam Iddriss, Patrick M. McCarthy, S. Chris Malaisrie, Allen Anderson, Jonathan D. Rich, Duc Thinh Pham
Article
Endocrinology & Metabolism
Israel Hodish, Afaf Absood, Leanza Liu, Ming Liu, Leena Haataja, Dennis Larkin, Ahmed Al-Khafaji, Anthony Zaki, Peter Arvan