Article
Biochemistry & Molecular Biology
Runzhong Fu, Maria C. Edman, Sarah F. Hamm-Alvarez
Summary: The study revealed that Rab27a is involved in the secretion of CTSS in lacrimal gland acinar cells through the regulated pathway of fusion and depletion of CTSS-enriched vesicles, as well as through a novel endolysosomal pathway increased in Sjogren's syndrome.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Physiology
Irene Ramos-Alvarez, Lingaku Lee, Robert T. Jensen
Summary: This study demonstrates that CCK can activate cofilin to promote enzyme secretion and MAPK activation in pancreatic acinar cells, indicating its important role in insulin secretion, pancreatic cancer cell growth, and pancreatitis.
FRONTIERS IN PHYSIOLOGY
(2023)
Article
Endocrinology & Metabolism
Ilka Wilhelmi, Stephan Grunwald, Niclas Gimber, Oliver Popp, Gunnar Dittmar, Anup Arumughan, Erich E. Wanker, Thomas Laeger, Jan Schmoranzer, Oliver Daumke, Annette Schuermann
Summary: The study reveals a previously unrecognized pathway required for insulin secretion at the level of trans-Golgi sorting, with GTPase ARFRP1 and GOPC regulating insulin secretion by controlling the plasma membrane localization of SNAP25.
MOLECULAR METABOLISM
(2021)
Article
Endocrinology & Metabolism
Katrina Viloria, Daniela Nasteska, Julia Ast, Annie Hasib, Federica Cuozzo, Silke Heising, Linford J. B. Briant, Martin Hewison, David J. Hodson
Summary: GC-globulin (GC), also known as vitamin D-binding protein, plays a multifunctional role in transporting vitamin 25(OH)D, fatty acids, and scavenging actin. It is highly localized to glucagon-secreting alpha-cells in the pancreatic islets. Loss of GC exacerbates alpha-cell failure during metabolic stress, leading to impaired glucagon secretion and changes in alpha-cell morphology. Restoring GC levels rescues the impairments in glucagon secretion and restores the F-actin cytoskeleton of alpha-cells. Decreased GC levels in alpha-cells of type 2 diabetes donors are associated with changes in alpha-cell mass, morphology, and glucagon expression.
Article
Neurosciences
Takahiro Takano, David I. Yule
Summary: The exocrine pancreas secretes fluid and digestive enzymes in response to parasympathetic release of acetylcholine and the gut hormone cholecystokinin. The secretion process is dependent on an increase in cytosolic calcium concentration. This study developed an in vivo method to observe pancreatic acinar calcium signals using a genetically expressed calcium indicator and multi-photon microscopy. The results showed that calcium signals in acinar cells are spatiotemporally regulated and disrupted in pathological conditions.
JOURNAL OF PHYSIOLOGY-LONDON
(2023)
Article
Multidisciplinary Sciences
Urska Marolt, Eva Paradiz Leitgeb, Viljem Pohorec, Saska Lipovsek, Viktoria Venglovecz, Eleonora Gal, Attila Ebert, Istvan Menyhart, Stojan Potrc, Marko Gosak, Jurij Dolensek, Andraz Stozer
Summary: The physiology and pathophysiology of the exocrine pancreas are closely related to changes in intracellular calcium concentration. The acute pancreas tissue slice technique is an effective method for evaluating the morphology and physiology of the pancreas in situ. This study used calcium imaging to characterize the responses of acinar cells to stimulation and compared the effects of different stimuli.
Article
Multidisciplinary Sciences
Linxiang Lan, Theodore Evan, Huafu Li, Aasia Hussain, E. Josue Ruiz, May Zaw Thin, Rute M. M. Ferreira, Hari Ps, Eva M. Riising, Yoh Zen, Jorge Almagro, Kevin W. Ng, Pablo Soro-Barrio, Jessica Nelson, Gabriela Koifman, Joana Carvalho, Emma L. Nye, Yulong He, Changhua Zhang, Anguraj Sadanandam, Axel Behrens
Summary: This study identifies BMP inhibitor GREM1 as a key regulator of cellular heterogeneity in pancreatic cancer. Continuous activity of GREM1 is required to maintain the stability of the epithelial PDAC subpopulations, while high activity of GREM1 can revert the mesenchymal fate of PDAC cells. By inhibiting the expression of epithelial-mesenchymal transition transcription factors, GREM1 restricts the epithelial-mesenchymal plasticity of pancreatic cancer cells.
Article
Multidisciplinary Sciences
Mari Kawaguchi, Yohei Okazawa, Aiko Imafuku, Yuko Nakano, Risa Shimizu, Reiji Ishizuka, Tianlong Jiang, Tatsuki Nagasawa, Junya Hiroi, Shigeki Yasumasu
Summary: This study reports the identification of a novel digestive enzyme called pactacin, belonging to the astacin metalloprotease family, specifically found in teleosts. Through analyzing pactacin enzymes in pot-bellied seahorse and medaka, it was discovered that these enzymes are commonly expressed in the pancreas and converted to active forms in the intestine. The findings suggest a unique digestive enzyme evolution in teleosts, with potential implications for understanding nutrient extraction in vertebrates.
SCIENTIFIC REPORTS
(2021)
Article
Hematology
Kerstin Schuetze, Miriam Gross, Kerstin Cornils, Katharina Wustrau, Sonja Schneppenheim, Henning Lenhartz, G. Christoph Korenke, Gritta Janka, Svea Ledig, Ingo Mueller, Stephan Ehl, Kai Lehmberg
Summary: Multiple hereditary forms of hemophagocytic lymphohistiocytosis (HLH) are caused by defects of cytotoxicity, including vesicle trafficking disorder Griscelli syndrome type 2 (GS2) and MADD deficiency, resulting in various syndromic features. This study demonstrates that MADD deficiency leads to a defect in cytotoxicity, contributing to the pathogenesis of HLH.
Article
Multidisciplinary Sciences
Miriam Lisci, Philippa R. Barton, Lyra O. Randzavola, Claire Y. Ma, Julia M. Marchingo, Doreen A. Cantrell, Vincent Paupe, Julien Prudent, Jane C. Stinchcombe, Gillian M. Griffiths
Summary: This study revealed that CTLs require mitochondria for target cell-killing, and this requirement is linked to mitochondrial translation. Inhibition of mitochondrial translation impairs CTL killing by triggering attenuated cytosolic translation, leading to a reduced capacity for sustained killing. Mitochondria emerge as a previously unappreciated homeostatic regulator of protein translation required for serial CTL killing.
Article
Multidisciplinary Sciences
Julian Terglane, Dirk Menche, Volker Gerke
Summary: This study demonstrates that the vacuolar-type H+-ATPase on Weibel-Palade bodies is necessary for proper acidification and maturation of the organelle.
Article
Gastroenterology & Hepatology
Anna Evans Phillips, Gong Tang, Xianling Wang, Christopher E. Forsmark, Dhiraj Yadav
Summary: This study investigated the prevalence and prescription patterns of pancreatic enzyme replacement therapy (PERT) use in individuals with non-pancreatic digestive conditions (NPDC). The results showed that a considerable number of NPDC patients receive PERT, but at lower doses and for shorter durations.
DIGESTIVE DISEASES AND SCIENCES
(2023)
Article
Endocrinology & Metabolism
Xinzhi Li, Yuze Jiang, Xu Sun, Yongsen Wu, Zheng Chen
Summary: This study found that under inflammatory and oxidative stress conditions, METTL3 is downregulated, and deletion of Mettl3 induces beta-cell failure and hyperglycemia. This suggests that METTL3 may be a potential drug target for the treatment of beta-cell failure in diabetes.
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)
Article
Endocrinology & Metabolism
Berit Svendsen, Jens J. Holst
Summary: The study shows a reciprocal feedback cycle between somatostatin and glucagon secretion, with somatostatin inhibiting glucagon secretion at low and high glucose levels, and glucagon stimulating somatostatin secretion via the glucagon and GLP-1 receptors.
Article
Biochemistry & Molecular Biology
Amy E. Rumora, Giovanni LoGrasso, Julia A. Haidar, Justin J. Dolkowski, Stephen I. Lentz, Eva L. Feldman
JOURNAL OF LIPID RESEARCH
(2019)
Meeting Abstract
Endocrinology & Metabolism
Bruce A. Perkins, Leif Erik Lovblom, Vera Bril, Maryam Ferdousi, Andrej Orszag, Katie Edwards, Nicola Pritchard, Anthony W. Russell, Cirous Dehghani, Daniele Pacaud, Kenneth Romanchuk, Jean Mah, Maria Jeziorska, Andrew Marshall, Roni M. Shtein, Rodica Pop-Busui, Stephen I. Lentz, Andrew J. Boulton, Mitra Tavakoli, Nathan Efron, Rayaz A. Malik
Article
Clinical Neurology
Jennifer Kollmer, Ute Hegenbart, Christoph Kimmich, Ernst Hund, Jan C. Purrucker, John M. Hayes, Stephen Lentz, Georges Sam, Johann M. E. Jende, Stefan O. Schoenland, Martin Bendszus, Sabine Heiland, Markus Weiler
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2020)
Meeting Abstract
Endocrinology & Metabolism
Amy Rumora, Giovanni Lograsso, Jackson D. McGrath, Stephen I. Lentz, Eva L. Feldman
Article
Ophthalmology
Mandy K. Losiewicz, Lynda Elghazi, Diane C. Fingar, Raju V. S. Rajala, Stephen Lentz, Patrice E. Fort, Steven F. Abcouwer, Thomas W. Gardner
EXPERIMENTAL EYE RESEARCH
(2020)
Article
Clinical Neurology
J. Kollmer, T. Kessler, G. Sam, J. M. Hayes, S. I. Lentz, S. Heiland, M. Bendszus, W. Wick, M. Weiler
Summary: This study quantified peripheral nerve lesions in SMA type 3 patients using magnetization transfer ratio (MTR) of the sciatic nerve and found that MTR can serve as a novel biomarker for evaluating nerve changes. Results showed that MTR and CSA of the sciatic nerve differed significantly between patients and healthy controls, with MTR correlating with clinical scores and CMAPs.
EUROPEAN JOURNAL OF NEUROLOGY
(2021)
Article
Multidisciplinary Sciences
Juliana Bragazzi Cunha, Jared S. Elenbaas, Dhiman Maitra, Ning Kuo, Rodrigo Azuero-Dajud, Allison C. Ferguson, Megan S. Griffin, Stephen Lentz, Jordan A. Shavit, M. Bishr Omary
Summary: Congenital erythropoietic porphyria is a rare genetic disorder with no specific treatment, but a potential repurposed therapeutic was identified through the development of a zebrafish model by researchers.
SCIENTIFIC REPORTS
(2021)
Article
Endocrinology & Metabolism
Bruce A. Perkins, Leif Erik Lovblom, Evan J. H. Lewis, Vera Bril, Maryam Ferdousi, Andrej Orszag, Katie Edwards, Nicola Pritchard, Anthony Russell, Cirous Dehghani, Daniele Pacaud, Kenneth Romanchuk, Jean K. Mah, Maria Jeziorska, Andrew Marshall, Roni M. Shtein, Rodica Pop-Busui, Stephen Lentz, Mitra Tavakoli, Andrew J. M. Boulton, Nathan Efron, Rayaz A. Malik
Summary: In this study, corneal nerve fiber length (CNFL) was found to be an effective indicator for predicting the development of diabetic peripheral neuropathy (DPN). It showed good predictive validity for identifying patients at higher risk of developing DPN similar to 6 years in the future.
Article
Biochemistry & Molecular Biology
D. Kazyken, S. I. Lentz, D. C. Fingar
Summary: Alkaline intracellular pH (pHi) serves as a previously unknown activator of mTORC2, leading to increased cell survival signaling and downstream activity.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Meeting Abstract
Biochemistry & Molecular Biology
Dubek Kazyken, Stephen Lentz, Maxwell Wadley, Diane C. Fingar
Article
Immunology
Sarah E. Elzinga, Rosemary Henn, Benjamin J. Murdock, Bhumsoo Kim, John M. Hayes, Faye Mendelson, Ian Webber-Davis, Sam Teener, Crystal Pacut, Stephen I. Lentz, Eva L. Feldman
Summary: Obesity, prediabetes, and diabetes are associated with neurodegenerative diseases, particularly Alzheimer's disease and Alzheimer's disease related dementias, through the activation of innate inflammatory signaling, potentially via the cGAS/STING pathway.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Neurosciences
Sarah E. Elzinga, Emily J. Koubek, John M. Hayes, A. Carter, Faye E. Mendelson, Ian Webber-Davis, Stephen I. Lentz, Eva L. Feldman
Summary: The prevalence of obesity, prediabetes, and diabetes is increasing, and they are linked to neurodegenerative diseases and cognitive impairment. The cGAS/STING pathway is involved in both metabolic dysfunction and neurodegenerative diseases. In this study, a murine model targeting the cGAS/STING pathway was established to study obesity- and prediabetes-induced cognitive impairment. The results showed sexually dimorphic responses to high-fat diet in cGAS knockout mice, possibly due to differences in microglial morphology and cognition.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2023)
Article
Chemistry, Analytical
Sivakumar Jeyarajan, Irina X. Zhang, Peter Arvan, Stephen I. Lentz, Leslie S. Satin
Summary: The levels of free calcium (Ca2+) in pancreatic beta cell organelles have been studied recently. Disturbances in these calcium pools under pathological conditions are associated with altered communication and dysfunction of the cells. A dual Ca2+ sensor, called DS-1, was designed to investigate subcellular Ca2+ signalling in beta cells, specifically between the endoplasmic reticulum (ER) and mitochondria. DS-1 successfully measured ER and mitochondrial Ca2+ in real time and exhibited expected functional properties.
Article
Physiology
Erwin R. Arias-Hervert, Nicole Xu, Meredith Njus, Geoff G. Murphy, Yanan Hou, John A. Williams, Stephen I. Lentz, Stephen A. Ernst, Edward L. Stuenkel
PHYSIOLOGICAL REPORTS
(2020)