Review
Biochemistry & Molecular Biology
Norikiyo Honzawa, Kei Fujimoto
Summary: Type 2 diabetes is caused by impaired insulin secretion and/or insulin resistance. Recent studies have shown loss of pancreatic beta-cell mass in human diabetic patients, as well as dedifferentiation and transdifferentiation of islet cells. Hyperglycemia inhibits FoxO1 expression and induces Ngn3 expression, leading to a new molecular mechanism explaining beta-cell plasticity.
Article
Endocrinology & Metabolism
Sara Ibrahim, Macey Johnson, Clarissa Hernandez Stephens, Jerry Xu, Rachel Moore, Andrea Mariani, Christopher Contreras, Farooq Syed, Raghavendra G. Mirmira, Ryan M. Anderson, Emily K. Sims
Summary: The study showed that miR-21 induces beta-cell dysfunction and loss of cellular differentiation by reducing the expression of mRNAs specifying beta-cell identity.
MOLECULAR METABOLISM
(2021)
Review
Biochemistry & Molecular Biology
Ziyin Zhang, Yue Gao, Zhuo-Xian Meng
Summary: Type 2 diabetes (T2D) is a disease caused by insulin resistance and insufficient insulin secretion. Pancreatic beta-cell dysfunction is the primary determinant of T2D progression and remission. Recent studies have shown that beta-cell dedifferentiation and reprogramming play important roles in the early and middle stages of T2D progression. Understanding the transcriptional control of beta-cell identity and plasticity can lead to the development of more effective strategies for treating T2D.
JOURNAL OF GENETICS AND GENOMICS
(2022)
Article
Biochemistry & Molecular Biology
Yasutaka Miyachi, Takashi Miyazawa, Yoshihiro Ogawa
Summary: Understanding the genetic factors of diabetes is crucial for addressing the global increase in type 2 diabetes. HNF1A mutations cause a form of monogenic diabetes called MODY, and HNF1A single-nucleotide polymorphisms are associated with the development of type 2 diabetes. The roles of HNF1A in insulin secretion, lipid metabolism, protein synthesis, and urinary glucose reabsorption have been explored through studies using genetically modified mice and human stem cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Endocrinology & Metabolism
Wenrui Wang, Chuan Zhang
Summary: The review focuses on the pathological characteristics of diabetes mellitus induced by various stressors or immune-mediated injuries, with a particular emphasis on the reduction of pancreatic islet beta-cell populations and activity. Current treatment strategies are ineffective in slowing disease progression, prompting ongoing research in genetically engineering beta-cell mimetics through bi-directional plasticity. The consensus points to beta-cell dedifferentiation as the primary cause of decreased beta-cell mass and activity, suggesting a potential therapeutic window for intervention. Additionally, exploring strategies for beta-cell regeneration using genetic programming, small molecules, cytokines, and bioengineering is discussed, along with the need for further studies to develop efficient reprogramming methods to generate fully functional beta-cells. Further investigations are deemed necessary to transform diabetes into a potentially curable disease.
ENDOCRINE CONNECTIONS
(2021)
Article
Endocrinology & Metabolism
Ciro Salinno, Maren Buettner, Perla Cota, Sophie Tritschler, Marta Tarquis-Medina, Aimee Bastidas-Ponce, Katharina Scheibner, Ingo Burtscher, Anika Boettcher, Fabian J. Theis, Mostafa Bakhti, Heiko Lickert
Summary: The study identified CD81 as a novel surface marker for labeling mature and immature pancreatic islet beta-cells, with different expression levels in different diabetic mouse models. This marker will aid in studying beta-cell heterogeneity in healthy and diabetic individuals more effectively.
MOLECULAR METABOLISM
(2021)
Article
Immunology
Floris Leenders, Nathalie Groen, Natascha de Graaf, Marten A. Engelse, Ton J. Rabelink, Eelco J. P. de Koning, Francoise Carlotti
Summary: Oxidative stress-induced dysfunction and partial dedifferentiation of human beta cells may be associated with the onset of diabetes. Targeting antioxidant mechanisms in the early stages of T1D development may help preserve functional beta-cell mass.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Yunbiao Lu, Rongrong Huang, Zhongkan Sun, Yu Ou
Summary: The study investigated the effects of lacto-ghrestatin derived nonapeptide (LGP9) on islet and β-cell dedifferentiation in type 2 diabetes mellitus (T2DM). Results showed that LGP9 improved β-cell dedifferentiation and acted via the PI3k/Akt/FOXO1 signaling pathway.
Article
Biology
Giuseppe Iurato, Abir U. Igamberdiev
Summary: This paper discusses the evolution of embryogenesis patterns and the discovery of cellular plasticity, highlighting the influence of epigenetic factors on cellular determination. Through the study of new biomolecular mechanisms, a greater understanding of the developmental process of cells can be achieved.
Article
Medicine, Research & Experimental
Yanting Yuan, Ji Zhou, Ruixin Hu, Linhai Zou, Lixia Ji, Guohui Jiang
Summary: Piperine significantly ameliorates the dedifferentiation and dysfunction of beta-cell by inhibiting the accumulation and M-1-like polarization of macrophages in visceral adipose tissues and islets.
Review
Biochemistry & Molecular Biology
Hong-Lian Wang, Li Wang, Chang-Ying Zhao, Hui-Yao Lan
Summary: Research has shown that TGF-beta signaling plays diverse roles in beta cell development, function, proliferation, and apoptosis, with Smad3 identified as a key mediator and ideal therapeutic target for type-2 diabetes. However, the effects of Smad7 on beta cell proliferation and glucose homeostasis remain controversial. Overexpression of Tgfb1 has been found to prevent beta cells from autoimmune destruction without affecting beta cell function. These findings highlight the complex regulatory roles of TGF-beta signaling in beta cell biology.
Article
Endocrinology & Metabolism
Cathleen D'Angelo, Hannah L. West, Nicholas B. Whitticar, Kathryn L. Corbin, Lauren M. Donovan, Benjamin Stiadle, Craig S. Nunemaker
Summary: Pulsatility is important for the development of islet function. Neonatal islets demonstrate different intracellular calcium patterns in response to glucose compared to adult islets, and these patterns become more mature as the islets develop. Understanding the role of pulsatility in islets may help in reversing beta-cell dedifferentiation and improving the function of beta cells derived from pluripotent stem cells.
Article
Endocrinology & Metabolism
Sneha S. Varghese, Sangeeta Dhawan
Summary: Cellular senescence is a complex process that results in permanent cell-cycle arrest in response to various stressors. It plays a crucial role in aging, disease development, embryogenesis, tissue regeneration, and tissue repair. Senescence is particularly important in pancreatic beta-cells, where it contributes to the decline in regenerative capacity and failure in diabetes. Understanding the molecular mechanisms of beta-cell senescence and its role in growth and development is significant for potential therapeutic interventions.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Review
Cell Biology
Ali H. Shilleh, Holger A. Russ
Summary: The use of stem-cell-derived insulin-producing beta-like cells (sBCs) as a cell replacement therapy holds promise for treating patients with type one diabetes. However, there is a lack of understanding regarding the fate of sBCs after transplantation, as studies have shown high loss rates similar to cadaveric human islets. This review explores potential mechanisms for the loss of sBCs in vivo and the importance of addressing this issue for successful transplantation.
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)
Article
Cell Biology
Qian Zhang, Challa Tenagne Delessa, Robert Augustin, Mostafa Bakhti, Gustav Collden, Daniel J. Drucker, Annette Feuchtinger, Cristina Garcia Caceres, Gerald Grandl, Alexandra Harger, Stephan Herzig, Susanna Hofmann, Cassie Lynn Holleman, Martin Jastroch, Susanne Keipert, Maximilian Kleinert, Patrick J. Knerr, Konxhe Kulaj, Beata Legutko, Heiko Lickert, Xue Liu, Gerd Luippold, Dominik Lutter, Emilija Malogajski, Marta Tarquis Medina, Stephanie A. Mowery, Andreas Blutke, Diego Perez-Tilve, Ciro Salinno, Laura Sehrer, Richard D. DiMarchi, Matthias H. Tschoep, Kerstin Stemmer, Brian Finan, Christian Wolfrum, Timo D. Mueller
Summary: The activation or inhibition of the glucose-dependent insulinotropic polypeptide receptor (GIPR) for the treatment of obesity remains uncertain. Studies show that CNS Gipr plays a key role in controlling energy metabolism, with activation or inhibition having significant effects on body weight and glucose metabolism.
Article
Biochemistry & Molecular Biology
Ingo Burtscher, Marta Tarquis-Medina, Ciro Salinno, Silvia Schirge, Julia Beckenbauer, Mostafa Bakhti, Heiko Lickert
Summary: Nkx6-1 is a key transcription factor in the regulation of motor neuron development, neuron specification, and pancreatic endocrine and beta-cell differentiation. The Nkx6-1-VF reporter protein accurately marks and tracks specific cell types, providing a unique tool for studying gene expression patterns during organ development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Endocrinology & Metabolism
Lena Oppenlaender, Subarna Palit, Kerstin Stemmer, Tobias Greisle, Michael Sterr, Ciro Salinno, Aimee Bastidas-Ponce, Annette Feuchtinger, Anika Boettcher, Ansarullah, Fabian J. Theis, Heiko Lickert
Summary: The study demonstrates the superiority of vertical sleeve gastrectomy (VSG) over calorie restriction in late-stage type 2 diabetes, rapidly restoring normal blood glucose levels. VSG induced distinct, intrinsic changes in the transcriptome of β-cells, leading to their fast redifferentiation and functional improvement post-intervention.
MOLECULAR METABOLISM
(2021)
Article
Endocrinology & Metabolism
Ciro Salinno, Maren Buettner, Perla Cota, Sophie Tritschler, Marta Tarquis-Medina, Aimee Bastidas-Ponce, Katharina Scheibner, Ingo Burtscher, Anika Boettcher, Fabian J. Theis, Mostafa Bakhti, Heiko Lickert
Summary: The study identified CD81 as a novel surface marker for labeling mature and immature pancreatic islet beta-cells, with different expression levels in different diabetic mouse models. This marker will aid in studying beta-cell heterogeneity in healthy and diabetic individuals more effectively.
MOLECULAR METABOLISM
(2021)
Article
Endocrinology & Metabolism
Nirav Florian Chhabra, Anna-Lena Amend, Aimee Bastidas-Ponce, Sibylle Sabrautzki, Marta Tarquis-Medina, Stephan Sachs, Marina Rubey, Bettina Lorenz-Depiereux, Annette Feuchtinger, Mostafa Bakhti, Heiko Lickert, Gerhard K. H. Przemeck, Martin Hrabe de Angelis
Summary: This study investigated the consequences of a point mutation in the Pdia6 gene on β-cell development and function in mice. The mutation led to hypoinsulinemia and hyperglycemia in adult mice, attributed to loss of β-cell function and identity. It was observed that mutant mice displayed reduced insulin-expressing β-cells and altered expression of key markers.
MOLECULAR METABOLISM
(2021)
Article
Biochemical Research Methods
Marius Lange, Volker Bergen, Michal Klein, Manu Setty, Bernhard Reuter, Mostafa Bakhti, Heiko Lickert, Meshal Ansari, Janine Schniering, Herbert B. Schiller, Dana Pe'er, Fabian J. Theis
Summary: Computational trajectory inference is a method to reconstruct cell state dynamics from single-cell RNA sequencing experiments, but it requires prior knowledge of the direction of biological processes. CellRank is a new approach that allows single-cell fate mapping in scenarios where the direction is unknown, such as regeneration, reprogramming, and disease.
Editorial Material
Endocrinology & Metabolism
Mostafa Bakhti, Heiko Lickert
Summary: In 2021, discoveries were made regarding the mechanisms of beta-cell failure in the progression of diabetes mellitus, validating new molecular targets for intervention. The field of stem-cell-derived beta-cell replacements is also rapidly advancing, bringing us closer to therapies that can protect and regenerate beta-cell mass.
NATURE REVIEWS ENDOCRINOLOGY
(2022)
Article
Multidisciplinary Sciences
Marten Plambeck, Atefeh Kazeroonian, Dirk Loeffler, Lorenz Kretschmer, Ciro Salinno, Timm Schroeder, Dirk H. Busch, Michael Flossdorf, Veit R. Buchholz
Summary: This study utilized continuous live-cell imaging to track the division speed and genealogical connections of a single naive CD8(+) T cell and its descendants. The results showed that T cell clonal expansion consists of a short burst phase with homogeneous fast division speed, followed by diversification of division speed and differentiation into memory and effector cells.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Mostafa Bakhti, Aimee Bastidas-Ponce, Sophie Tritschler, Oliver Czarnecki, Marta Tarquis-Medina, Eva Nedvedova, Katharina Scheibner, Jessica Jaki, Perla Cota, Ciro Salinno, Karsten Boldt, Stefanie J. Willmann, Nicola Horn, Marius Ueffing, Ingo Burtscher, Fabian J. Theis, Unal Coskun, Heiko Lickert
Summary: The authors found that Synaptotagmin-13 plays a role in remodeling cell-matrix adhesion to regulate the formation of pancreatic islets of Langerhans. Syt13 is specifically upregulated in endocrine precursors and is involved in the repolarization of endocrine precursor cells during their egression. Knockout of Syt13 impairs endocrine cell egression and alters the alpha-to-beta-cell ratio.
NATURE COMMUNICATIONS
(2022)
Article
Endocrinology & Metabolism
Carmelo Quarta, Kerstin Stemmer, Aaron Novikoff, Bin Yang, Felix Klingelhuber, Alex Harger, Mostafa Bakhti, Aimee Bastidas-Ponce, Eric Bauge, Jonathan E. Campbell, Megan Capozzi, Christoffer Clemmensen, Gustav Collden, Perla Cota, Jon Douros, Daniel J. Drucker, Barent DuBois, Annette Feuchtinger, Cristina Garcia-Caceres, Gerald Grandl, Nathalie Hennuyer, Stephan Herzig, Susanna M. Hofmann, Patrick J. Knerr, Konxhe Kulaj, Fanny Lalloyer, Heiko Lickert, Arek Liskiewicz, Daniela Liskiewicz, Gandhari Maity, Diego Perez-Tilve, Sneha Prakash, Miguel A. Sanchez-Garrido, Qian Zhang, Bart Staels, Natalie Krahmer, Richard D. DiMarchi, Matthias H. Tschoep, Brian Finan, Timo D. Mueller
Summary: A conjugate drug consisting of a GLP-1 receptor agonist and a PPAR alpha/gamma dual-agonist called tesaglitazar has been found to be more effective in treating diabetes compared to monotherapy. The drug utilizes GLP-1 receptor-dependent cellular delivery of tesaglitazar, leading to improved body weight, food intake, and glucose metabolism. It may be a promising treatment option for hyperglycemia and insulin resistance.