Review
Cell & Tissue Engineering
Nathaniel J. Hogrebe, Matthew Ishahak, Jeffrey R. Millman
Summary: The generation of islet-like endocrine clusters from human pluripotent stem cells (hPSCs) has great potential for diabetes treatment. To be widely adopted, highly functional and well-characterized stem cell-derived islets (SC-is-lets) need to be manufactured at scale. This review discusses recent advances in generating and characterizing SC-is-lets, as well as strategies to ensure graft viability and safety after transplantation.
Review
Endocrinology & Metabolism
Meghan Tahbaz, Eiji Yoshihara
Summary: Insulin injection and human pancreatic islet transplantation are current main therapies for T1D or late-stage severe T2D, but limitations such as islet shortage and immunosuppression side effects call for the need to develop novel methods for generating protected functional human islets. Human pluripotent stem cells offer a potentially limitless cell source, and studying immune tolerance induction in hPSC-derived human pancreatic islets contributes to the goal of curing insulin-dependent diabetes.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Physiology
Shichen Huang, Zhiyuan Li, Yuhan Sun, Baiyi Chen, Yuxin Jiang, Feng Hong
Summary: CD34 could serve as a biomarker for islet beta-cells, with its expression and number being inversely correlated with islet alpha-cells. This suggests the potential of CD34 as a diagnostic biomarker for early diabetes.
FRONTIERS IN PHYSIOLOGY
(2022)
Review
Cardiac & Cardiovascular Systems
Jerome Robert
Summary: Endothelial cells are crucial for vascular homeostasis and play a vital role in controlling blood flow, immune cell trafficking, and vascular growth and repair. Dysfunction of endothelial cells, characterized by impaired secretion of vasodilator molecules, increased reactive oxygen species, expression of adhesion molecules, and secretion of proinflammatory cytokines, leads to cardiovascular diseases. Sex hormones, such as estrogens, androgens, and progestogens, regulate endothelial functions. However, gender also influences endothelial cell physiology at the genetic level.
Review
Endocrinology & Metabolism
Peter J. Thompson, Jasmine Pipella, Guy A. Rutter, Herbert Y. Gaisano, Pere Santamaria
Summary: Type 1 diabetes occurs when the body's immune system mistakenly attacks and destroys pancreatic beta cells. This review highlights recent advances in understanding how early life exposures and stress response pathways impact beta cells and contribute to the autoimmune process in type 1 diabetes. Progress in this area holds promise for developing targeted therapies that could be implemented in the early stages of the disease, potentially in combination with immunotherapies.
Article
Cell Biology
Annie R. Pineros, Abhishek Kulkarni, Hongyu Gao, Kara S. Orr, Lindsey Glenn, Fei Huang, Yunlong Liu, Maureen Gannon, Farooq Syed, Wenting Wu, Cara M. Anderson, Carmella Evans-Molina, Marcia McDuffie, Jerry L. Nadler, Margaret A. Morris, Raghavendra G. Mirmira, Sarah A. Tersey
Summary: This study suggests that inflammatory signaling in beta cells promotes autoimmunity during the progression of type 1 diabetes. By deleting a specific proinflammatory gene in mice, the researchers found that the preservation of beta cell mass and reduction in infiltrating T cell populations protected against spontaneous autoimmune diabetes.
Article
Cell Biology
Marta Perez-Frances, Maria Valentina Abate, Delphine Baronnier, Philipp E. Scherer, Yoshio Fujitani, Fabrizio Thorel, Pedro L. Herrera
Summary: This study investigates the developmental dynamics of pancreatic islet endocrine cell types using murine models. The researchers find that adult islet cells originate from embryonic hormone-expressing cells and there is no evidence of islet cell differentiation from precursor cells after birth. The study also reveals specific patterns of hormone gene activation and switching during islet morphogenesis.
Article
Endocrinology & Metabolism
Xinzhi Li, Ying Yang, Zhenzhi Li, Yuqin Wang, Jingting Qiao, Zheng Chen
Summary: This study aims to investigate the role of WTAP in the regulation of islet beta cell failure and diabetes. It was found that WTAP is downregulated in islet beta cells in type 2 diabetes, and its loss leads to beta cell failure and diabetes. Furthermore, WTAP was found to maintain beta cell function by regulating m(6)A mRNA modification depending on METTL3 expression.
Article
Medicine, Research & Experimental
Chandan Sona, Yu-Te Yeh, Andreas Patsalos, Laszlo Halasz, Xin Yan, Natalia L. Kononenko, Laszlo Nagy, Matthew N. Poy
Summary: Through single-cell RNA sequencing analysis, this study found increased CADM1(+) cells adjacent to CD8(+) T cells in the islets of individuals with T1D and those who were autoantibody-positive, indicating that CADM1-mediated intercellular contact may facilitate the infiltration of cytotoxic T lymphocytes and could serve as a potential therapeutic target for preventing T1D pathogenesis.
Article
Medicine, Research & Experimental
Abhishek Kulkarni, Annie R. Pineros, Melissa A. Walsh, Isabel Casimiro, Sara Ibrahim, Marimar Hernandez-Perez, Kara S. Orr, Lindsey Glenn, Jerry L. Nadler, Margaret A. Morris, Sarah A. Tersey, Raghavendra G. Mirmira, Ryan M. Anderson
Summary: Macrophages and related myeloid cells play a crucial role in the early pathogenesis of T1D, with 12-LOX identified as a key enzyme promoting islet inflammation. Depletion of 12-LOX results in reduced macrophage infiltration, preservation of beta cell mass, and protection from T1D development in zebrafish and NOD mice models. The defect in myeloid cell migration caused by 12-LOX depletion is attributed to the loss of the chemokine receptor CXCR3. Transgenic expression of CXCR3 rescues the migratory defect.
Review
Endocrinology & Metabolism
Raza Ali Naqvi, Afsar Raza Naqvi, Amar Singh, Medha Priyadarshini, Appakalai N. N. Balamurugan, Brian T. T. Layden
Summary: Replacement of beta cells and induction of pluripotent stem cells hold promise for curing type 1 diabetes, but challenges need to be resolved cautiously.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Multidisciplinary Sciences
Leon van Gurp, Leon Fodoulian, Daniel Oropeza, Kenichiro Furuyama, Eva Bru-Tari, Anh Nguyet Vu, John S. Kaddis, Ivan Rodriguez, Fabrizio Thorel, Pedro L. Herrera
Summary: The authors used single-cell transcriptomics meta-analysis to construct gene sets that accurately describe the identity of various human islet cells. These gene sets have proven effective in analyzing cell identity changes and their underlying genetic mechanisms, providing reliable tools for cell therapy and diabetes treatment.
NATURE COMMUNICATIONS
(2022)
Review
Endocrinology & Metabolism
Alexandra Kautzky-Willer, Michael Leutner, Jurgen Harreiter
Summary: The prevalence of type 2 diabetes is increasing in both sexes, but men are diagnosed at a younger age and lower body fat mass than women. Worldwide, there are about 17.7 million more men than women with diabetes. Women are at a greater risk for obesity at the time of type 2 diabetes diagnosis and psychosocial stress may play a more prominent role in their diabetes risk.
Article
Cardiac & Cardiovascular Systems
Sadiya S. Khan, Lauren B. Beach, Clyde W. Yancy
Summary: Sex-based differences in risk, symptoms, and management of heart failure exist, with women having a higher incidence of HF with preserved ejection fraction compared to men. However, there are gaps in understanding gender-based differences in HF and inadequate representation of women and gender minorities in clinical trials.
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
(2022)
Article
Immunology
Sudhanshu Agrawal, Jon Salazar, Thu Michelle Tran, Anshu Agrawal
Summary: Evidence suggests that females exhibit a stronger immune response to SARS-CoV-2 within 24 hours of infection compared to males, with higher activation of cells and levels of inflammatory factors in female individuals.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Cell Biology
Dana M. Previte, Christina P. Martins, Erin C. O'Connor, Meghan L. Marre, Gina M. Coudriet, Noah W. Beck, Ashley Menk, Rebecca H. Wright, Hubert M. Tse, Greg M. Delgoffe, Jon D. Piganelli
Editorial Material
Endocrinology & Metabolism
Justin A. Spanier, Hubert M. Tse, Marc S. Horwitz, Brian T. Fife
FRONTIERS IN ENDOCRINOLOGY
(2019)
Article
Endocrinology & Metabolism
Jessie M. Barra, Veronika Kozlovskaya, Eugenia Kharlampieva, Hubert M. Tse
Article
Endocrinology & Metabolism
Guang Ren, Teayoun Kim, Hae-Suk Kim, Martin E. Young, Donald D. Muccio, Venkatram R. Atigadda, Samuel I. Blum, Hubert M. Tse, Kirk M. Habegger, Sushant Bhatnagar, Tatjana Coric, Mary-Ann Bjornsti, Anath Shalev, Stuart J. Frank, Jeong-a Kim
Review
Microbiology
Samuel Blum, Hubert M. Tse
Article
Multidisciplinary Sciences
Ashley E. Landuyt, Barbara J. Klocke, Lennard W. Duck, Keri M. Kemp, Rachel Q. Muir, Melissa S. Jennings, Samuel Blum, Hubert M. Tse, Goo Lee, Casey D. Morrow, Charles O. Elson, Craig L. Maynard
Summary: ICOSLG gene is associated with inflammatory bowel disease susceptibility, playing a critical role in adaptive immune regulation of the microbiota in the large intestine through its partnership with IL-10. Deficiency of ICOSL leads to enrichment of IL-10-producing CD4 T cells and impaired antibody recognition of microbial antigens.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Biotechnology & Applied Microbiology
Hubert M. Tse, Graeme Gardner, Juan Dominguez-Bendala, Christopher A. Fraker
Summary: Oxygen plays a crucial role in cell culture, influencing cell proliferation, differentiation, and function. As technology advances, it is increasingly recognized that cell culture is not a one-size-fits-all process, and individual cell types may have specific oxygen requirements. Utilizing different oxygen supply systems can improve potential issues in cell culture processes.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Stephanie B. Wall, Rui Li, Brittany Butler, Ashley R. Burg, Hubert M. Tse, Jennifer L. Larson-Casey, A. Brent Carter, Clyde J. Wright, Lynette K. Rogers, Trent E. Tipple
Summary: The gold compound AFN suppresses IL-1β synthesis by activating NRF2 directly, independent of NFκB and glutathione-mediated antioxidant mechanisms. NRF2 binding to the promoter region of IL1β inhibits transcription of the IL1β gene.
Article
Medicine, Research & Experimental
Jessie M. Barra, Veronika Kozlovskaya, Jessica D. Kepple, Karen L. Seeberger, Purushothaman Kuppan, Chad S. Hunter, Gregory S. Korbutt, Eugenia Kharlampieva, Hubert M. Tse
Summary: The study demonstrated the efficacy of encapsulating neonatal porcine islets to decrease inflammatory innate immune signals and improve islet function following xenotransplantation. The encapsulation material suppressed reactive oxygen species synthesis and modulated immune responses, leading to restoration of euglycemia in experimental mice.
XENOTRANSPLANTATION
(2021)
Article
Biochemistry & Molecular Biology
Jared P. Taylor, Hubert M. Tse
Summary: NADPH oxidases (NOX) are enzymes that produce superoxide or hydrogen peroxide by utilizing NADPH, playing important roles in various biological functions. Among the NOX family, NOX2 regulates innate and adaptive immunity, while DUOX1 and DUOX2 are crucial in innate immune defenses at epithelial barriers. Targeting NOX enzymes or scavenging free radicals may be beneficial in treating autoimmune diseases and acute lung injury.
Article
Medicine, Research & Experimental
Jessica D. Kepple, Jessie M. Barra, Martin E. Young, Chad S. Hunter, Hubert M. Tse
Summary: Transplanting islets into brown adipose tissue (BAT) may be a viable alternative transplant site that improves graft survival and delays immune rejection.
Article
Multidisciplinary Sciences
Guanlan Xu, Tiffany D. Grimes, Truman B. Grayson, Junqin Chen, Lance A. Thielen, Hubert M. Tse, Peng Li, Matt Kanke, Tai-Tu Lin, Athena A. Schepmoes, Adam C. Swensen, Vladislav A. Petyuk, Fernando Ovalle, Praveen Sethupathy, Wei-Jun Qian, Anath Shalev
Summary: Oral verapamil lowers inflammatory markers and daily insulin needs in subjects with type 1 diabetes and helps preserve pancreatic beta cell function for at least two years. Verapamil normalizes serum CHGA levels and reverses T1D-induced elevations in circulating proinflammatory T-follicular-helper cell markers. RNA-sequencing further confirms that verapamil regulates the thioredoxin system and promotes an anti-oxidative, anti-apoptotic, and immunomodulatory gene expression profile in human islets.
NATURE COMMUNICATIONS
(2022)
Article
Endocrinology & Metabolism
Mei-Ling Yang, Sean E. Connolly, Renelle J. Gee, TuKiet T. Lam, Jean Kanyo, Jian Peng, Perrin Guyer, Farooq Syed, Hubert M. Tse, Steven G. Clarke, Catherine F. Clarke, Eddie A. James, Cate Speake, Carmella Evans-Molina, Peter Arvan, Kevan C. Herold, Li Wen, Mark J. Mamula
Summary: In this study, the researchers found a group of carbonylated proteins in pancreatic islets before the onset of hyperglycemia in NOD mice. They discovered that carbonylated prolyl-4-hydroxylase beta subunit (P4Hb) is an autoantigen in both human and murine type 1 diabetes. They also found that carbonylated P4Hb is increased in stressed islets, leading to decreased insulin secretion and altered proinsulin-to-insulin ratios. Autoantibodies against P4Hb were detected in prediabetic NOD mice and early human type 1 diabetes patients. Additionally, the researchers identified autoreactive CD4(+) T-cell responses toward carbonyl-P4Hb epitopes in the circulation of patients with type 1 diabetes. These findings provide mechanistic insight into the pathways of proinsulin metabolism and the formation of autoantigens in type 1 diabetes.
Article
Surgery
Jessie M. Barra, Veronika Kozlovskaya, KaLia S. Burnette, Ronadip R. Banerjee, Christopher A. Fraker, Eugenia Kharlampieva, Hubert M. Tse
Summary: The study explores the use of islet encapsulation technologies to enhance graft survival and function in type 1 diabetes without systemic immunosuppression. The encapsulation with TA, PVPON, and CTLA-4-Ig leads to localized immunosuppression and prolongs islet allograft function. This is achieved by suppressing proinflammatory macrophage and T cell responses, enhancing regulatory T cells, and inhibiting T cell activation.
AMERICAN JOURNAL OF TRANSPLANTATION
(2023)
Article
Multidisciplinary Sciences
Alexandra Martin, Gail J. Mick, Heather M. Choat, Alison A. Lunsford, Hubert M. Tse, Gerald G. McGwin, Kenneth L. McCormick
Summary: This study aimed to evaluate the safety and efficacy of oral GABA alone or in combination with GAD on the preservation of residual insulin secretion in recent-onset T1D. The results showed that neither GABA alone nor the combination of GABA and GAD-alum could preserve beta-cell function.
NATURE COMMUNICATIONS
(2022)
Article
Endocrinology & Metabolism
Liujun Chen, Lisha Li, Donghong Cui, Yiheng Huang, Haibin Tong, Haleh Zabihi, Shuxia Wang, Yadan Qi, Ted Lakowski, Lin Leng, Suixin Liu, Hong Wu, Lawrence H. Young, Richard Bucala, Dake Qi
Summary: Attenuation of adipose hormone sensitive lipase (HSL) may impair lipolysis and exacerbate obesity. Cytokine macrophage migration inhibitory factor (MIF) plays a role in regulating adipose HSL and adipocyte hypertrophy. Both intracellular and extracellular MIF have opposing effects on HSL, but extracellular action predominates to downregulate HSL and exacerbate obesity development during high-fat diet (HFD).
MOLECULAR METABOLISM
(2024)
Article
Endocrinology & Metabolism
Mengyang Tang, Yi Zhang, Rong Zhang, Yuemei Zhang, Jiangfei Zheng, Daixi Wang, Xinyu Wang, Jing Yan, Cheng Hu
Summary: This study aimed to explore the role of GPSM1 in POMC neurons and the underlying mechanisms in metabolic homeostasis. Through various molecular, biochemical, immunofluorescent, immunohistochemical analyses, and cell culture studies, the study revealed the pathophysiological role of GPSM1 in POMC neurons and its regulation of POMC neuron activity.
MOLECULAR METABOLISM
(2024)
