Review
Endocrinology & Metabolism
Mario A. Miranda, Juan F. Macias-Velasco, Heather A. Lawson
Summary: The review examines the heterogeneity of pancreatic beta-cells from morphological, functional, and transcriptional perspectives, considering factors such as topography, maturation, development, and stress response. It discusses the identification of beta-cell subtypes and how heterogeneity is influenced by diabetes. The paper also explores open questions in the field and recent technological innovations that could advance understanding of beta-cell heterogeneity in health and disease.
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
(2021)
Review
Endocrinology & Metabolism
Zijing Chen, Leah Truskinovsky, Emmanuel S. Tzanakakis
Summary: This review discusses the application of optical methods, including optogenetics, optochemical, and photopharmacological strategies, in pancreatic cells and tissues. It highlights the potential of these methods in regulating insulin secretion and controlling blood sugar levels. Optical methods offer greater precision and controllability compared to traditional drugs, providing new possibilities for addressing pancreatic pathologies.
MOLECULAR METABOLISM
(2022)
Review
Biochemistry & Molecular Biology
Akinobu Nakamura
Summary: SGLT2 inhibitors not only lower blood glucose levels but also have protective effects on organs such as the heart and kidneys. These inhibitors prevent beta-cell dysfunction by reducing glucose overload, leading to increased beta-cell proliferation and decreased apoptosis. Clinical and preclinical data support the protective effect of SGLT2 inhibitors on beta-cell mass and function.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Noura Aldous, Abu Saleh Md Moin, Essam M. Abdelalim
Summary: Recent studies have shown that pancreatic beta-cells are heterogeneous in their transcriptional profiles and insulin secretion abilities. Different sub-populations of beta-cells have been identified based on functionality and surface markers. Understanding the heterogeneity of beta-cells and their interactions with other endocrine cells is crucial for developing stem cell-derived therapies for diabetes.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
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
Cell Biology
Eva Tuduri, Sergi Soriano, Lucia Almagro, Eduard Montanya, Paloma Alonso-Magdalena, Angel Nadal, Ivan Quesada
Summary: This review summarizes the age-related alterations, adaptations, and failures of pancreatic β-cells at the molecular, morphological, and functional levels in both mice and humans. The findings suggest that changes in β-cell proliferation, apoptosis, and function with age may impact the development of type 2 diabetes.
AGEING RESEARCH REVIEWS
(2022)
Review
Food Science & Technology
Camelia Papuc, Gheorghe V. Goran, Corina N. Predescu, Liliana Tudoreanu, Georgeta Stefan
Summary: Diabetes is a metabolic disorder characterized by high blood sugar levels with detrimental effects on various systems. Plant polyphenols have shown beneficial activity for diabetes prevention and treatment. This review article summarizes the mechanisms by which polyphenols decrease insulin resistance and inhibit loss of pancreatic islet beta-cell mass and function, as well as their effects on insulin release.
CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION
(2022)
Article
Toxicology
Jenna E. Todero, Kieran Koch-Laskowski, Qing Shi, Matt Kanke, Yu-Han Hung, Rowan Beck, Miroslav Styblo, Praveen Sethupathy
Summary: Arsenic, a pervasive environmental toxin, can cause type 2 diabetes through chronic exposure. This study reveals that arsenic treatment impairs insulin secretion in pancreatic beta cells and alters the microRNA profile. Multi-omic analysis shows that arsenic affects pathways related to insulin secretion and diabetes, and different forms of arsenic have distinct effects on cell cycle and beta cell maintenance factors. miR-29a is identified as a potential master regulator of these genes.
ARCHIVES OF TOXICOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Tomonori Tsuyama, Yoshifumi Sato, Tatsuya Yoshizawa, Takaaki Matsuoka, Kazuya Yamagata
Summary: Hypoxia-induced transcriptional repressor BHLHE40 suppresses insulin secretion by inhibiting the expression of MAFA in beta-cells.
Article
Cell Biology
Erwin Ilegems, Galyna Bryzgalova, Jorge Correia, Burcak Yesildag, Edurne Berra, Jorge L. Ruas, Teresa S. Pereira, Per-Olof Berggren
Summary: This study found the presence of HIF-1 alpha in pancreatic cells during the progression of type 2 diabetes, and demonstrated that treatment with the HIF-1 alpha inhibitor PX-478 can improve beta cell function, prevent diabetes progression, and increase insulin secretion. The results showed that PX-478 treatment has an improving effect on mouse and human islets.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Review
Endocrinology & Metabolism
Nivedita Seshadri, Christine A. Doucette
Summary: Beta cell dysfunction is central to the development of type 2 diabetes, and circadian disruption has emerged as an important environmental risk factor for T2D. Genetic disruption of the circadian timing system impairs insulin secretion and triggers diabetes development, highlighting the essential role of the circadian timing system in the regulation of pancreatic beta cell function.
Article
Pharmacology & Pharmacy
Suhadinie Gamage, Mirabela Hali, Anjaneyulu Kowluru
Summary: CARD9 plays a crucial role in regulating insulin secretion, potentially through a Rac1-independent and p38-dependent signaling module.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Michala Prause, Signe Schultz Pedersen, Violeta Tsonkova, Min Qiao, Nils Billestrup
Summary: Butyrate has been shown to prevent cytokine-induced dysfunction in pancreatic beta cells, potentially reducing the impact of inflammation in the progression of T2D. However, it may also affect cell proliferation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Anna Weiser, Jerome N. Feige, Umberto De Marchi
Summary: Accumulation of calcium in energized mitochondria of pancreatic beta-cells plays a crucial role in beta-cell function. Mitochondrial calcium signaling is important for regulating insulin secretion and new pharmacological and genetic findings provide potential intervention strategies for modulating pancreatic beta-cell function in the context of diabetes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Han Zhu, Gaowei Wang, Kim-Vy Nguyen-Ngoc, Dongsu Kim, Michael Miller, Georgina Goss, Jenna Kovsky, Austin R. Harrington, Diane C. Saunders, Alexander L. Hopkirk, Rebecca Melton, Alvin C. Powers, Sebastian Preissl, Francesca M. Spagnoli, Kyle J. Gaulton, Maike Sander
Summary: By analyzing the single-cell transcriptomes and accessible chromatin profiles, we compared the differentiation process of pancreatic islet cells derived from human pluripotent stem cells with those from childhood and adult donors. We identified major cell types, defined their regulomes, and described the spatiotemporal gene regulatory relationships between transcription factors. Our study revealed CDX2 as a regulator of enterochromaffin-like cells and provided evidence against the proposed non-pancreatic origin. Additionally, we observed insufficient activation of signal-dependent transcriptional programs during in vitro beta cell maturation and identified sex hormones as drivers of beta cell proliferation in childhood.
DEVELOPMENTAL CELL
(2023)
Article
Biology
Satvika Burugupalli, Adam Alexander T. Smith, Gavriel Oshlensky, Kevin Huynh, Corey Giles, Tingting Wang, Alexandra George, Sudip Paul, Anh Nguyen, Thy Duong, Natalie Mellett, Michelle Cinel, Sartaj Ahmad Mir, Li Chen, Markus R. Wenk, Neerja Karnani, Fiona Collier, Richard Saffery, Peter Vuillermin, Anne-Louise Ponsonby, David Burgner, Peter Meikle
Summary: This study investigates the impact of antenatal factors on lipid metabolism in infancy, as well as the changes in lipid metabolism during early childhood and the effects of breastfeeding. The findings contribute to a better understanding of lipid metabolism in early life and provide insights for early interventions.
Article
Biology
Toby Mansell, Richard Saffery, Satvika Burugupalli, Anne-Louise Ponsonby, Mimi L. K. Tang, Martin O'Hely, Siroon Bekkering, Adam Alexander T. Smith, Rebecca Rowland, Sarath Ranganathan, Peter D. Sly, Peter Vuillermin, Fiona Collier, Peter Meikle, David Burgner
Summary: The study found that infants with a higher infection burden in the first year of life had proinflammatory and proatherogenic plasma metabolomic/lipidomic profiles at 12 months, indicating potentially modifiable pathways linking early life infection and inflammation with subsequent cardiometabolic risk.
Review
Physiology
Yvette L. L. Schooneveldt, Sudip Paul, Anna C. C. Calkin, Peter J. J. Meikle
Summary: Ether lipids are a unique class of lipids that play important roles in regulating various physiological processes and providing protection, and they have been found to be associated with obesity.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Canchen Ma, Ming Liu, Jing Tian, Guangju Zhai, Flavia Cicuttini, Yvette L. Schooneveldt, Peter J. Meikle, Graeme Jones, Feng Pan
Summary: This study identified three novel lipid signatures for persistent multisite musculoskeletal pain, suggesting that lipid metabolism is involved in the pathogenesis of persistent pain.
Article
Cardiac & Cardiovascular Systems
Wei Wu, Qun Lu, Shan Ma, Jin-Chan Du, Kevin Huynh, Thy Duong, Zhang-Da Pang, Daniel Donner, Peter J. Meikle, Xiu-Ling Deng, Xiao-Jun Du
Summary: Using an isoproterenol-induced mouse model of Takotsubo syndrome (TTS), we investigated the role of the O-adrenoceptors (OAR)-Hippo signaling pathway in mediating mitochondrial dysfunction. Our findings demonstrate that activation of OAR stimulates the Hippo pathway, which leads to mitochondrial dysfunction characterized by energy insufficiency and increased reactive oxygen species.
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
(2023)
Article
Endocrinology & Metabolism
Guillaume Treiber, Alice Guilleux, Kevin Huynh, Oriane Bonfanti, Ania Flaus-Furmaniuk, David Couret, Natalie Mellet, Celine Bernard, Nathalie Le-Moullec, Berenice Doray, Isabelle Jeru, Jean-Christophe Maiza, Bhoopendrasing Domun, Muriel Cogne, Olivier Meilhac, Corinne Vigouroux, Peter J. Meikle, Estelle Nobecourt
Summary: The study investigated glucose tolerance, insulin response, and metabolic markers in FPLD2 patients, revealing a high prevalence of diabetes and prediabetes. Early diagnosis and treatment are necessary.
DIABETES & METABOLISM
(2023)
Review
Biology
Aaron W. Jurrjens, Marcus M. Seldin, Corey Giles, Peter J. Meikle, Brian G. Drew, Anna C. Calkin
Summary: Cardiometabolic diseases result from genetic, environmental, and lifestyle factors and identifying those at high risk is challenging. Systems genetics, using population-based approaches, can elucidate the genetic and environmental causes of these diseases. Mouse genetic reference panels provide a complementary approach to human genome-wide association studies, allowing for controlled investigation of genetic and phenotypic variation. Integrating multi-omics data from human and mouse populations can advance our understanding of cardiometabolic diseases.
Article
Biochemistry & Molecular Biology
Dantong Zhu, Stephen T. Vernon, Zac D'Agostino, Jingqin Wu, Corey Giles, Adam S. Chan, Katharine A. Kott, Michael P. Gray, Alireza Gholipour, Owen Tang, Habtamu B. Beyene, Ellis Patrick, Stuart M. Grieve, Peter J. Meikle, Gemma A. Figtree, Jean Y. H. Yang
Summary: The current CAD risk scores based on traditional risk factors often fail individuals. We aim to identify lipidomic biomarkers using non-invasive imaging technology and advanced lipidomic measurement to enable intervention before cardiovascular events.
Article
Multidisciplinary Sciences
Le May Thai, Liam O'Reilly, Saskia Reibe-Pal, Nancy Sue, Holly Holliday, Lewin Small, Carsten Schmitz-Peiffer, Rama Dhenni, Vicky Wang-Wei Tsai, Nicholas Norris, Belinda Yau, Xuan Zhang, Kailun Lee, Chenxu Yan, Yan-Chuan Shi, Melkam A. Kebede, Robert Brink, Gregory J. Cooney, Katharine M. Irvine, Samuel N. Breit, Tri G. Phan, Alexander Swarbrick, Trevor J. Biden
Summary: This study focuses on using islet-associated macrophages (IAMs) as a model to study resident macrophage function under physiological conditions. It was found that IAMs play a role in regulating glucose-stimulated insulin secretion (GSIS) through metabolic rewiring and engagement of Axl receptors. High-fat feeding stimulates efferocytosis in IAMs, which impairs GSIS and potentially contributes to beta-cell dysfunction in pre-diabetes.
Article
Nutrition & Dietetics
Paige F. van der Pligt, Konsita Kuswara, Sarah A. Mcnaughton, Gavin Abbott, Sheikh Mohammed Shariful Islam, Kevin Huynh, Peter J. Meikle, Aya Mousa, Stacey J. Ellery
Summary: This study aimed to assess the relationship between early pregnancy maternal diet quality and maternal plasma lipids and indicators of cardiometabolic health. The results showed that maternal diet quality was inversely associated with multiple plasma triglycerides. This study provides novel insights into the relationship between diet quality, lipid biomarkers, and cardiometabolic health during pregnancy.
EUROPEAN JOURNAL OF NUTRITION
(2023)
Article
Gastroenterology & Hepatology
Ying Li, Bhagirath Chaurasia, M. Mahidur Rahman, Vincent Kaddai, J. Alan Maschek, Jordan A. Berg, Joseph L. Wilkerson, Ziad S. Mahmassani, James Cox, Peng Wei, Peter J. Meikle, Donald Atkinson, Liping Wang, Annelise M. Poss, Mary C. Playdon, Trevor S. Tippetts, Esraa M. Mousa, Kesara Nittayaboon, Pon Velayutham Anandh Babu, Micah J. Drummond, Hans Clevers, James A. Shayman, Yoshio Hirabayashi, William L. Holland, Jared Rutter, Bruce A. Edgar, Scott A. Summers
Summary: This study found that ceramides, as sphingolipid compounds, are associated with alimentary tract cancers. They function as signals of nutritional excess and can alter stem cell behaviors to influence cancer risk. The study also discovered that sphingolipid-producing enzymes are up-regulated in intestinal adenomas, leading to increased proliferation of intestinal progenitors through the stimulation of peroxisome-proliferator activated receptor-alpha and induction of fatty acid binding protein-1.
Article
Cell Biology
Hyo Lee, Aimee J. Aylward, Richard Pearse II, Alexandra M. Lish, Yi-Chen Hsieh, Zachary M. Augur, Courtney R. Benoit, Vicky Chou, Allison Knupp, Cheryl Pan, Srilakshmi Goberdhan, Duc M. Duong, Nicholas T. Seyfried, David A. Bennett, Mariko F. Taga, Kevin Huynh, Matthias Arnold, Peter J. Meikle, Philip L. De Jager, Vilas Menon, Jessica E. Young, Tracy L. Young-Pearse
Summary: SORL1 plays an important role in the pathogenesis of Alzheimer's disease. Loss of SORL1 affects neurons and astrocytes the most and leads to a reduction in apolipoprotein E (APOE) and clusterin (CLU), altered lipid profiles, and tau phenotypes in neurons. The study also identifies a link between SORL1, APOE, and CLU levels in neurons and implicates transforming growth factor β/SMAD signaling in SORL1 function.
Article
Multidisciplinary Sciences
Ebru Boslem, Saskia Reibe, Rodrigo Carlessi, Benoit Smeuninx, Surafel Tegegne, Casey L. Egan, Emma Mclennan, Lauren V. Terry, Max Nobis, Andre Mu, Cameron Nowell, Neil Horadagoda, Natalie A. Mellett, Paul Timpson, Matthew Jones, Elena Denisenko, Alistair R. R. Forrest, Janina E. E. Tirnitz-Parker, Peter J. Meikle, Stefan Rose-John, Michael Karin, Mark A. Febbraio
Summary: The incidence of hepatocellular carcinoma (HCC) is increasing due to obesity-related nonalcoholic steatohepatitis (NASH). In a mouse model mimicking NASH-driven HCC, activation of endoplasmic reticulum stress and inflammation was observed in hepatocytes. Treatment with an ER stress inhibitor and an anti-inflammatory drug reversed NASH and reduced NASH-driven HCC.
Article
Medicine, General & Internal
Taeho Jo, Junpyo Kim, Paula Bice, Kevin Huynh, Tingting Wang, Matthias Arnold, Peter J. Meikle, Corey Giles, Rima Kaddurah-Daouk, Andrew J. Saykin, Kwangsik Nho
Summary: This study introduces the Circular-Sliding Window Association Test (c-SWAT) to improve the classification accuracy in predicting Alzheimer's Disease (AD) using serum-based metabolomics data. The results show that c-SWAT is effective in improving classification accuracy and in identifying key lipids associated with AD.
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)