Article
Endocrinology & Metabolism
Shiuhwei Chen, ZhiJiang Huang, Harrison Kidd, Min Kim, Eul Hyun Suh, Shangkui Xie, Ebrahim H. Ghazvini Zadeh, Yan Xu, A. Dean Sherry, Philipp E. Scherer, Wen-hong Li
Summary: Appropriate insulin secretion is crucial for maintaining euglycemia and understanding the dynamics of insulin secretion at the cellular level in intact pancreas of living animals remains challenging. Through ZIMIR imaging, insulin/Zn2+ release of individual islet beta-cells can be tracked with high spatiotemporal resolution, revealing synchronized rhythmic secretion activity. Additionally, the use of chemogenetic approach and fluorescent granule zinc indicator show promise for selective and efficient islet cell labeling in living animals.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Multidisciplinary Sciences
Maryam Saadati, Yousef Jamali
Summary: The study demonstrates that defects in beta-cell mass can lead to functional decline in individual beta-cells, impairment in intra-islet synchrony, and changes in oscillatory patterns of membrane potential and intracellular Ca2+ concentration, thereby affecting insulin secretion dynamics and levels. Additionally, inter-beta-cellular electrical coupling is shown to play a more important role in regulating islet function and in the development of human T2D.
SCIENTIFIC REPORTS
(2021)
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
Biochemistry & Molecular Biology
Kristen E. Rohli, Cierra K. Boyer, Sandra E. Blom, Samuel B. Stephens
Summary: Pancreatic islet beta-cells have the ability to adapt their secretory program to match nutrient availability and peripheral insulin signaling cues. However, as Type 2 diabetes progresses, these adaptive mechanisms fail, leading to a decline in beta-cell function and impaired insulin secretion.
Article
Biochemistry & Molecular Biology
Yinling Chen, Jianxin Jia, Qing Zhao, Yuxian Zhang, Bingkun Huang, Likun Wang, Juanjuan Tian, Caoxin Huang, Mingyu Li, Xuejun Li
Summary: In this study, a novel HNF1a variant (HNF1a-Q125ter) was found to cause beta-cell dysfunction through activating the PERK/eIF2a/ATF4 signaling pathway.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Endocrinology & Metabolism
Jean-Claude Henquin
Summary: Optimal metabolic homeostasis requires precise control of insulin secretion, which is influenced by various factors. Inconsistent findings between in vitro and clinical studies may result from extreme experimental conditions that do not reflect physiological relevance.
METABOLISM-CLINICAL AND EXPERIMENTAL
(2021)
Article
Environmental Sciences
Hin Ting Wan, Lok Yi Cheung, Ting Fung Chan, Marco Li, Keng Po Lai, Chris Kong Chu Wong
Summary: Considerable human data have shown that exposure to PFOS is correlated with the risk of metabolic diseases, but the underlying effects are not clearly understood. This study investigated the impact of PFOS treatment on pancreatic beta-cell functions, revealing inhibitory effects on insulin secretion and disruptions in energy metabolism pathways.
ENVIRONMENTAL POLLUTION
(2021)
Review
Biochemistry & Molecular Biology
Shun-ichiro Asahara, Hiroyuki Inoue, Hitoshi Watanabe, Yoshiaki Kido
Summary: Pancreatic beta-cells are the only cells that can control glycemic levels through insulin secretion. Studies have found that mTOR plays a significant role in the function of beta-cells and the progression of diabetes.
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
Biology
Melissa T. Adams, JaeAnn M. Dwulet, Jennifer K. Briggs, Christopher A. Reissaus, Erli Jin, Joseph M. Szulczewski, Melissa R. Lyman, Sophia M. Sdao, Vira Kravets, Sutichot D. Nimkulrat, Suzanne M. Ponik, Matthew J. Merrins, Raghavendra G. Mirmira, Amelia K. Linnemann, Richard K. P. Benninger, Barak Blum
Summary: This study demonstrates that altered islet spatial architecture in Robo beta KO mice leads to reduced synchronized Ca2+ oscillations among beta cells, suggesting that the islet architecture itself is required for synchronized insulin secretion. The findings have implications for understanding the structure-function relationships in islets during progression to diabetes and in engineering islets from stem cells.
Article
Endocrinology & Metabolism
Glenn M. Ward, Jacqueline M. Walters, Judith L. Gooley, Raymond C. Boston
Summary: The authors discuss modifications made to glucose challenge protocols and mathematical models in order to estimate insulin secretion, insulin sensitivity, and glucose effectiveness in patients with Insulin-Requiring Diabetes and those who received Pancreatic Islet Transplants for Type I diabetes. The evolution of protocols and models for use in Type I Diabetes and Insulin-Requiring Type 2 Diabetes that were the basis for studies in Islet Recipients is outlined. The ongoing application of adaptations is helping to clarify Islet pathophysiology in Islet Transplant Recipients.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Multidisciplinary Sciences
S. N. Patel, M. Ishahak, D. Chaimov, A. Velraj, D. LaShoto, D. W. Hagan, P. Buchwald, E. A. Phelps, A. Agarwal, C. L. Stabler
Summary: This study highlights the importance of a dynamic in vitro microenvironment for preserving the function of primary organoid models and demonstrates the utility of the MPS for in situ multiparametric assessment.
Article
Multidisciplinary Sciences
Henriette Frikke-Schmidt, Peter Arvan, Randy J. Seeley, Corentin Cras-Meneur
Summary: This study successfully tracked and quantified insulin content in up to two hundred individual islets simultaneously during a glucose challenge. The research found that while isolated islets respond homogeneously to glucose in culture, their profiles differ significantly in vivo. Some islets respond sharply to a glucose stimulation while others barely secrete at all.
SCIENTIFIC REPORTS
(2021)
Article
Endocrinology & Metabolism
Selina Wrublewsky, Thimoteus Speer, Lisa Nalbach, Anne S. Boewe, Mandy Pack, Dalia Alansary, Leticia P. Roma, Markus D. A. Hoffmann, Beate M. Schmitt, Andrea Weinzierl, Michael D. Menger, Matthias W. Laschke, Emmanuel Ampofo
Summary: The inhibition of NLRP3 improves the survival and endocrine function of pancreatic islet grafts by enhancing revascularization and inducing insulin gene expression. This inhibition has significant therapeutic potential in pancreatic islet transplantation.
Review
Pharmacology & Pharmacy
Anjaneyulu Kowluru, Noah F. Gleason
Summary: The Rho subfamily of G proteins, particularly Rac1, plays a crucial role in glucose-stimulated insulin secretion from pancreatic beta-cells. Metabolic stress, such as chronic exposure to high glucose, can lead to sustained activation of Rac1, resulting in oxidative stress, impaired insulin secretion, and beta-cell dysfunction. The regulation of G protein activation and deactivation is mediated by GEFs, GAPs, and GDIs, with GDIs playing essential roles in G protein function and subcellular targeting for effector activation and cell regulation.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Medicine, Research & Experimental
Arne Hinrichs, Evamaria O. Riedel, Nikolai Klymiuk, Andreas Blutke, Elisabeth Kemter, Matthias Laengin, Maik Dahlhoff, Barbara Kessler, Mayuko Kurome, Valeri Zakhartchenko, Eva-Maria Jemiller, David Ayares, Martin Bidlingmaier, Florian Flenkenthaler, Martin Hrabe de Angelis, Georg J. Arnold, Bruno Reichart, Thomas Froehlich, Eckhard Wolf
Summary: Genetically modified GHR-KO donor pigs showed significantly reduced body weight and heart weight compared to controls, indicating the potential for using them in xenotransplantation to prevent xeno-organ overgrowth. Offspring from the quadruple-modified (4GM) pigs exhibited expected genetic modifications and consistent transgene expression.
XENOTRANSPLANTATION
(2021)
Article
Immunology
Isabella-Maria Giese, Marie-Christin Schilloks, Roxane L. Degroote, Maria Weigand, Simone Renner, Eckhard Wolf, Stefanie M. Hauck, Cornelia A. Deeg
Summary: The study found reduced proliferative response in T cells and distinct changes in protein abundances in CD4(+) T cells of diabetic pigs. Additionally, altered metabolic immune cell phenotype with increased mitochondrial oxygen consumption rate and higher basal glycolytic activity was observed in PBMC of diabetic pigs. The research provides new insights into molecular mechanisms of dysregulated immune cells triggered by permanent hyperglycemia.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Vera A. van der Weijden, Meret Schmidhauser, Mayuko Kurome, Johannes Knubben, Veronika L. Floter, Eckhard Wolf, Susanne E. Ulbrich
Summary: Our study found that in vivo developed and in vitro produced embryos show similar transcriptome profiles during development. Shared canonical pathways in transitions from 4-cell to morula included oxidative phosphorylation and EIF2 signaling, while shared pathways from morula to hatched blastocyst included 14-3-3-mediated signaling, xenobiotic metabolism general signaling pathway, and NRF2-mediated oxidative stress response. Hatched blastocysts from in vitro fertilization-pipeline exhibited molecular pathways associated with lower developmental competence compared to in vivo developed embryos.
Review
Biochemistry & Molecular Biology
Christian Kupatt, Alina Windisch, Alessandra Moretti, Eckhard Wolf, Wolfgang Wurst, Maggie C. Walter
Summary: Mutations in the Dystrophin gene cause Duchenne Muscular Dystrophy, a severe muscle disease affecting both skeletal muscles and the heart. Various molecular therapies have been developed, and genome editing using CRISPR-Cas9 offers a novel option for correcting these mutations.
Article
Multidisciplinary Sciences
Beate Rieblinger, Hicham Sid, Denise Duda, Tarik Bozoglu, Romina Klinger, Antonina Schlickenrieder, Kamila Lengyel, Krzysztof Flisikowski, Tatiana Flisikowska, Nina Simm, Alessandro Grodziecki, Carolin Perleberg, Andrea Bahr, Lucie Carrier, Mayuko Kurome, Valeri Zakhartchenko, Barbara Kessler, Eckhard Wolf, Lutz Kettler, Harald Luksch, Ibrahim T. Hagag, Daniel Wise, Jim Kaufman, Benedikt B. Kaufer, Christian Kupatt, Angelika Schnieke, Benjamin Schusser
Summary: Research on genetically modified animals has mostly focused on mice, but also includes species like pigs that are more physiologically similar to humans, and cross-species comparisons with phylogenetically distant species like chickens. CRISPR-Cas9 is a versatile genetic editing method applicable across various species. The successful generation of transgenic chickens and pigs that express Cas9 in all organs has confirmed the functionality of Cas9 across different target genes, cell types, and in vivo applications.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Cell Biology
Michael Walz, Christine Hoeflich, Christina Walz, Daniela Ohde, Julia Brenmoehl, Mandy Sawitzky, Andreas Vernunft, Uwe K. Zettl, Susanne Holtze, Thomas B. Hildebrandt, Eckhard Wolf, Andreas Hoeflich
Summary: The bioactivity of the IGF system is regulated by IGFBPs, IGFBP proteases, and inhibitors. The effects of the IGF system on the AKT/mTOR pathway are of interest. Using IGFBP2 to enhance the sensitivity of IGF-dependent bioactivity, phosphorylation of AKT-Ser473 was assessed as a readout of pathway activity.
Article
Endocrinology & Metabolism
Felicia Gerst, Elisabeth Kemter, Estela Lorza-Gil, Gabriele Kaiser, Ann-Kathrin Fritz, Rita Nano, Lorenzo Piemonti, Marie Gauder, Andreas Dahl, Silvio Nadalin, Alfred Koenigsrainer, Falko Fend, Andreas L. Birkenfeld, Robert Wagner, Martin Heni, Norbert Stefan, Eckhard Wolf, Hans-Ulrich Haering, Susanne Ullrich
Summary: The decline of fetuin-A levels during perinatal period may relieve TGFBR signaling in islets, facilitating functional maturation of neonatal beta cells. However, elevated plasma fetuin-A levels in later life can impair both function and adaptive proliferation of beta cells, leading to a reduction in functional beta cell mass and an acceleration of the onset of type 2 diabetes.
Article
Multidisciplinary Sciences
Natalie Theobalt, Isabel Hofmann, Sonja Fiedler, Simone Renner, Georg Dhom, Annette Feuchtinger, Axel Walch, Martin Hrabe de Angelis, Eckhard Wolf, Ruediger Wanke, Andreas Blutke
Summary: In translational obesity research, LSFM is demonstrated as an effective tool for accurate analysis of adipocyte volumes and numbers, providing valuable data for evaluating intervention efficacies.
Article
Cell Biology
Daniela Bebbere, Susanne E. Ulbrich, Katrin Giller, Valeri Zakhartchenko, Horst-Dieter Reichenbach, Myriam Reichenbach, Paul J. Verma, Eckhard Wolf, Sergio Ledda, Stefan Hiendleder
Summary: The study reveals about 50% reduction in mitochondrial DNA (mtDNA) in the liver and skeletal muscle of SCNT fetuses at day 80 of gestation, with no significant decrease observed in the brain. The depletion of mtDNA is associated with hepatomegaly and muscle hypertrophy of SCNT fetuses, indicating that it is a major signature of perturbations after SCNT. The expression of selected nuclear-encoded genes pivotal for mtDNA replication is similar to controls, suggesting that the mitochondrial perturbation in interaction with incomplete nuclear reprogramming drives abnormal epigenetic features and correlated phenotypes.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Sarah Duin, Shreya Bhandarkar, Susann Lehmann, Elisabeth Kemter, Eckhard Wolf, Michael Gelinsky, Barbara Ludwig, Anja Lode
Summary: The transplantation of pancreatic islets can prevent complications in diabetes patients. 3D bioprinting can encapsulate islets and improve the success rate of transplantation. This study successfully bioprinted neonatal porcine islet-like cell clusters and demonstrated their functionality in vitro.
Article
Nutrition & Dietetics
Rosamaria Lugara, Simone Renner, Eckhard Wolf, Annette Liesegang, Rupert Bruckmaier, Katrin Giller
Summary: Excessive intake of fats and sugars in the Western diet is a major cause of obesity. This study investigated the effects of Western diet and spirulina supplementation on gestating and lactating domestic pigs as a model for metabolic disturbances. The results suggest that domestic pigs have limited suitability as a model for Western diet-induced metabolic impairments, but low-dose spirulina supplementation can partially attenuate the negative effects.
Article
Biochemistry & Molecular Biology
Elena E. E. Wolf, Anne Steglich, Friederike Kessel, Hannah Kroeger, Jan Sradnick, Simone Reichelt-Wurm, Kathrin Eidenschink, Miriam C. C. Banas, Eckhard Wolf, Ruediger Wanke, Florian Gembardt, Vladimir T. T. Todorov
Summary: PLVAP serves as an early marker of glomerular endothelial injury in diabetic kidney disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Valerie Pauly, Julia Vlcek, Zhihao Zhang, Nora Hesse, Ruibing Xia, Julia Bauer, Simone Loy, Sarah Schneider, Simone Renner, Eckhard Wolf, Stefan Kaeaeb, Dominik Schuettler, Philipp Tomsits, Sebastian Clauss
Summary: Atrial fibrillation (AF) is a common arrhythmia caused by myocardial ischemia/infarction (MI). Men have a higher prevalence of AF, while women have a higher risk of new onset AF after MI. The impact of sex on AF pathophysiology is largely unknown. In pigs with/without ischemic heart failure (IHF), both male and female pigs showed increased vulnerability to AF. Male pigs had more and longer AF episodes, while female pigs had sinus node dysfunction.
Article
Biochemistry & Molecular Biology
Marie-Christin Schilloks, Isabella-Maria Giese, Arne Hinrichs, Lucia Korbonits, Stefanie M. Hauck, Eckhard Wolf, Cornelia A. Deeg
Summary: This study investigated the effects of impaired GHR signaling on immune functions and immunometabolism in GHR-KO pigs. The results showed significant differences in the relative proportion of the CD4(+)CD8a(-) subpopulation and IFN-a levels between GHR-KO pigs and WT controls. However, no significant difference was found in the respiratory capacity and the capacity for polyclonal stimulation in PBMCs between the two groups. Proteome analysis revealed multiple significant protein abundance differences related to amino acid metabolism, beta-oxidation of fatty acids, insulin secretion signaling, and oxidative phosphorylation between GHR-KO pigs and WT pigs.
Review
Developmental Biology
Claudia Springer, Eckhard Wolf, Kilian Simmet
Summary: Preimplantation development is well conserved across mammalian species, but differences in developmental kinetics and regulation of early lineage differentiation require further studies in different model organisms. Large domestic species like cattle and pigs resemble human development in many aspects, making them valuable models for studying early embryonic development.
JOURNAL OF DEVELOPMENTAL BIOLOGY
(2021)
