Article
Gastroenterology & Hepatology
Lai Wei, Rajan Singh, Se Eun Ha, Alyce M. Martin, Lauren A. Jones, Byungchang Jin, Brian G. Jorgensen, Hannah Zogg, Tyler Chervo, Andres Gottfried-Blackmore, Linda Nguyen, Aida Habtezion, Nick J. Spencer, Damien J. Keating, Kenton M. Sanders, Seungil Ro
Summary: The study utilized a transgenic mouse line specific to EC cells to investigate the pathophysiologic roles of 5-HT deficiency in gastric motility. Findings indicated a new mechanism of 5-HT deficiency in idiopathic gastroparesis.
Article
Medicine, General & Internal
Julio Rosenstock, Carol Wysham, Juan P. Frias, Shizuka Kaneko, Clare J. Lee, Laura Fernandez Lando, Huzhang Mao, Xuewei Cui, Chrisanthi A. Karanikas, Vivian T. Thieu
Summary: Tirzepatide demonstrated significant improvements in glycemic control and body weight without increasing the risk of hypoglycemia. The safety profile was consistent with GLP-1 receptor agonists, suggesting a potential monotherapy use for the treatment of type 2 diabetes.
Article
Medicine, General & Internal
Soyeon Yoo, Dongkyu Kim, Gwanpyo Koh
Summary: The study investigated changes in glucagon levels in people with diabetes after meal ingestion, finding that poorly controlled patients may have a greater increase in postprandial glucagon levels, which is not mediated by incretin.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Endocrinology & Metabolism
Ryan J. Jalleh, Laurence G. Trahair, Tongzhi Wu, Scott Standfield, Christine Feinle-Bisset, Christopher K. Rayner, Michael Horowitz, Karen L. Jones
Summary: This study aimed to evaluate the effect of gastric distension on the secretion of GIP and GLP-1 in healthy individuals. The results showed that gastric distension did not significantly stimulate the secretion of GLP-1 and GIP, regardless of the presence or absence of small intestinal nutrients.
DIABETES OBESITY & METABOLISM
(2023)
Article
Endocrinology & Metabolism
Simon Veedfald, Jens F. Rehfeld, Gerrit van Hall, Lars B. Svendsen, Jens J. Holst
Summary: The study investigated the rapid entero-pancreatic hormone secretion after nutrient ingestion and its correlation with gastric emptying and glucose absorption. Findings showed characteristic differences in timing and amplitude of early postprandial hormone responses, emphasizing the need to consider individual variations when interpreting mean responses and designing study protocols.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Article
Food Science & Technology
Alessandro Toffolon, Maurizio de Rocco-Ponce, Monica Vettore, Elisabetta Iori, Anna Lante, Paolo Tessari
Summary: Reversing the whey protein/casein ratio in cow-milk enhances the insulin response, potentially mediated by incretins and/or amino acids. These findings could be useful for designing specific milk formulas with different effects on insulin and incretin responses.
MOLECULAR NUTRITION & FOOD RESEARCH
(2021)
Article
Endocrinology & Metabolism
Martin Haljeta Friedrichsen, Lars Endahl, Frederik Flindt Kreiner, Ronald Goldwater, Martin Kankam, Soren Toubro, Sune Boris Nygard
Summary: NNC9204-1177 (NN1177) is a glucagon/glucagon-like peptide-1 (GLP-1) receptor co-agonist used for weight loss treatment. This study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of NN1177 through three phase 1 trials. While NN1177 showed some efficacy in weight loss, it also presented several treatment-related safety signals.
MOLECULAR METABOLISM
(2023)
Article
Pharmacology & Pharmacy
Zhuanglong Xiao, Jing Xu, Jun Tan, Shengyan Zhang, Nian Wang, Ruiyun Wang, Pengcheng Yang, Tao Bai, Jun Song, Zhaohong Shi, Wenliang Lyu, Lei Zhang, Xiaohua Hou
Summary: Zhizhu Kuanzhong (ZZKZ) is a traditional Chinese medicine that has been widely used in clinical therapy for functional dyspepsia (FD). This study aimed to evaluate the pharmacological effects and mechanisms of action of ZZKZ on gastric hypersensitivity and motor dysfunction in a rat model of FD. The results showed that ZZKZ improved FD-related gastric hypersensitivity and motor dysfunction, and the gastric 5-HT system with lower 5-HT3 activity and increased 5-HT4 distribution was involved in the mechanisms of ZZKZ underlying the treatment of FD.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Jelena Osmanovic Barilar, Ana Knezovic, Jan Homolak, Ana Babic Perhoc, Melita Salkovic-Petrisic
Summary: The incretin system plays an important role in the research of diabetes, obesity, and neurodegenerative disorders. This study investigates the effects of central GLP-1 and GIP on brain cell metabolism and energy, as well as the levels of these hormones and insulin in healthy rats and a rat model of Alzheimer's disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Aleksandra Grozic, Keaton Coker, Christopher M. Dussik, Marya S. Sabir, Zhela Sabir, Arianna Bradley, Lin Zhang, Jin Park, Steven Yale, Ichiro Kaneko, Maryam Hockley, Lucinda A. Harris, Tisha N. Lunsford, Todd R. Sandrin, Peter W. Jurutka
Summary: This study aimed to identify potential biomarkers and unique gene expression patterns that define the pathological state of irritable bowel syndrome (IBS). Gene expression profiling of colonic tissue samples from 29 participants, including IBS patients and healthy controls, revealed 858 differentially expressed genes potentially characteristic of IBS. After screening and analysis, seven putative IBS biomarkers, including genes involved in serotonin metabolism, were identified.
Review
Immunology
Gaber El-Saber Batiha, Hayder M. Al-kuraishy, Ali I. Al-Gareeb, Nada A. Ashour, Walaa A. Negm
Summary: In Covid-19 patients, variations in fasting blood glucose are considered a distinct risk factor for a negative prognosis. Tirazepatide (TZT), a dual GLP-1 and GIP receptor agonist, may be effective in managing Covid-19-induced hyperglycemia in both diabetic and non-diabetic patients.
INFLAMMOPHARMACOLOGY
(2023)
Article
Fisheries
Yiyang Tang, Mengzhe Feng, Xianyu Zhu, Jinjing Long, Zejun Zhou, Shaojun Liu
Summary: Glucagon-like peptide 2 (GLP2) plays a role in regulating energy absorption and maintaining intestinal mucosal integrity in fish. This study investigated the function of GLP2 in the intestinal barrier and immune defense of a hybrid crucian carp. The results suggest that WR-GLP2 is involved in the intestinal mucosal barrier and immune defense against pathogen infection, through inducing the expression of antimicrobial molecules and alleviating intestinal apoptosis.
FISH & SHELLFISH IMMUNOLOGY
(2022)
Article
Sport Sciences
Yung-Chih Chen, Jean-Philippe Walhin, Aaron Hengist, Javier T. Gonzalez, James A. Betts, Dylan Thompson
Summary: Interrupting prolonged sitting with intermittent walking can increase postprandial GLP-1 and PYY concentrations in healthy middle-age men and women with central adiposity.
MEDICINE & SCIENCE IN SPORTS & EXERCISE
(2022)
Article
Biochemistry & Molecular Biology
Marta Santos-Hernandez, Maria Cermeno, Isidra Recio, Richard J. FitzGerald
Summary: Dietary proteins play a role in regulating glucose homeostasis through inhibiting DPP-IV, inducing incretin secretion, or directly stimulating insulin secretion. Casein and whey proteins exhibit potent DPP-IV inhibitory activities, while gastric digests do not induce insulin secretion.
Article
Chemistry, Multidisciplinary
Siqi Wang, Yuqiong Wang, Long Lin, Zongjie Li, Fengyi Liu, Long Zhu, Jie Chen, Nianrong Zhang, Xinyu Cao, Sunman Ran, Genzheng Liu, Peng Gao, Weiliang Sun, Liang Peng, Jian Zhuang, Hua Meng
Summary: Intramuscular injection of BTX-A through dissolving microneedles in the gastric wall layers shows promising results in weight loss and metabolic improvement.
Article
Allergy
Xiao Tang, Elin Ronnberg, Jesper Safholm, Madhuranayaki Thulasingam, Mette Trauelsen, Thue W. Schwartz, Craig E. Wheelock, Sven-Erik Dahlen, Gunnar Nilsson, Jesper Z. Haeggstrom
Summary: SUCNR1 amplifies IgE-receptor-induced mast cell activation and allergic bronchoconstriction, suggesting a role for this pathway in aggravation of allergic asthma. Pharmacologically targeting protein kinase C and extracellular signal-regulated kinase can modulate succinate-potentiated mast cell reactivity.
Article
Chemistry, Medicinal
Michael Luckmann, Aslihan Shenol, Tinne A. D. Nissen, Jacob E. Petersen, David Kouvchinov, Thue W. Schwartz, Thomas M. Frimurer
Summary: The free fatty acid receptors FFAR1 and FFAR4 hold potential as therapeutic targets for metabolic and inflammatory diseases. However, the pharmaceutical industry has abandoned many lipophilic compounds due to toxic effects. A recent discovery by our group involves a compound that acts as an allosteric agonist on FFAR1. In this study, we present the synthesis and structure-activity relationship investigation of analogues displaying dual-acting agonist properties for both FFAR1 and FFAR4. Multiple analogues with high potency on FFAR1 have been discovered, offering new ways to achieve beneficial glycemic control without toxic side effects.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Multidisciplinary Sciences
Randi Bonke Mikkelsen, Tulika Arora, Kajetan Trost, Oksana Dmytriyeva, Sune Kjaersgaard Jensen, Abraham Stijn Meijnikman, Louise Elisabeth Olofsson, Dimitra Lappa, Omrum Aydin, Jens Nielsen, Victor Gerdes, Thomas Moritz, Arnold van de Laar, Maurits de Brauw, Max Nieuwdorp, Siv Annegrethe Hjorth, Thue Walter Schwartz, Fredrik Backhed
Summary: This study found that 3-hydroxydecanoate is enriched in the circulation of obese individuals with type 2 diabetes and is associated with chronic inflammation. Administration of 3-hydroxydecanoate to mice promotes immune cell recruitment to adipose tissue, leading to adipose inflammation and increased insulin levels. Furthermore, 3-hydroxydecanoate stimulates migration of human and mouse neutrophils through GPR84 and Gai signaling.
Article
Endocrinology & Metabolism
Ahmed M. Abdelmoez, Oksana Dmytriyeva, Yasemin-Xiomara Zurke, Mette Trauelsen, Alesandra A. Marica, Mladen Savikj, Jonathon A. B. Smith, Claudia Monaco, Thue W. Schwartz, Anna Krook, Nicolas J. Pillon
Summary: Succinate released by skeletal muscle activates SUCNR1/GPR91, but it is unclear which cell types respond to succinate and the directionality of communication. This study found that SUCNR1 is expressed in macrophages but not in muscle cells, suggesting that the adaptive response of skeletal muscle to exercise is mediated via paracrine mechanisms involving macrophages.
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
(2023)
Article
Cardiac & Cardiovascular Systems
Maria J. Forteza, Martin Berg, Andreas Edsfeldt, Jangming Sun, Roland Baumgartner, Ilona Kareinen, Felipe Beccaria Casagrande, Ulf Hedin, Song Zhang, Ivan Vuckovic, Petras P. Dzeja, Konstantinos A. Polyzos, Anton Gistera, Mette Trauelsen, Thue W. Schwartz, Lea Dib, Joerg Herrmann, Claudia Monaco, Ljubica Matic, Isabel Goncalves, Daniel F. J. Ketelhuth
Summary: Recent studies have shown a link between cellular metabolism and the chronic inflammatory process of atherosclerosis. The PDK/PDH axis has been identified as a major metabolic pathway regulating vascular inflammation and atherogenesis, and targeting it with DCA could be a promising treatment for atherosclerosis.
CARDIOVASCULAR RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Anna Katrina Jogvansdottir Gradel, Stephanie K. K. Holm, Sarah Byberg, Myrte Merkestein, Wouter Frederik Johan Hogendorf, Mari Lilith Lund, Jesse Arnold Buijink, Jesper Damgaard, Jens Lykkesfeldt, Birgitte Holst
Summary: Ghrelin is a key hormone regulating energy balance, while LEAP2 acts as an endogenous antagonist of the GHSR. This study found that different meal challenges and diets can regulate the expression and secretion of LEAP2 in the small intestine and liver.
Article
Chemistry, Medicinal
Corinna Schuess, Oanh Vu, Nigam M. Mishra, Iain R. Tough, Yu Du, Jan Stichel, Helen M. Cox, C. David Weaver, Jens Meiler, Kyle A. Emmitte, Annette G. Beck-Sickinger
Summary: In this study, a novel positive allosteric modulator (PAM) VU0506013 targeting the Y4R receptor was identified. It showed nanomolar affinity and selectivity towards the Y4R and has potential for anti-obesity research.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Dimitra M. Lappa, Abraham S. Meijnikman, Kimberly A. Krautkramer, Lisa M. Olsson, Omrum Aydin, Anne-Sophie Van Rijswijk, Yair I. Z. E. Acherman, Maurits De Brauw, Valentina A. Tremaroli, Louise E. Olofsson, Annika Lundqvist, Siv A. K. Hjorth, Boyang W. Ji, Victor E. A. Gerdes, Albert K. Groen, Thue W. Schwartz, Max Nieuwdorp, Fredrik Baeckhed, Jens Nielsen
Summary: Weight loss through bariatric surgery is effective in treating or preventing obesity related diseases, but the long-term weight loss response varies among patients. This study conducted multiple omics analyses on individuals undergoing bariatric surgery to identify metabolic differences and explore their relationship with weight loss response. Five distinct metabotypes were identified based on plasma metabolome analysis, showing differential enrichment in pathways related to immune functions, fatty acid metabolism, protein signaling, and obesity pathogenesis. The gut metagenome of the heavily medicated metabotypes was significantly enriched in Prevotella and Lactobacillus species. Each metabotype responded differently to bariatric surgery in terms of weight loss after 12 months. This study provides a path for patient stratification and improved clinical treatments.
Article
Nutrition & Dietetics
Silvia Lopez-Escalera, Mari L. L. Lund, Gerben D. A. Hermes, Beatrice S. -Y. Choi, Kei Sakamoto, Anja Wellejus
Summary: Non-alcoholic fatty liver disease (NAFLD) is a metabolic disorder that is associated with various health issues and is expected to increase in prevalence. Disturbance of tight junction proteins can lead to increased gut permeability and the passage of harmful microbial components to the liver, triggering inflammation and cellular stress. Targeted probiotic supplements have been proposed as a preventive therapy to improve gut barrier function and promote beneficial effects on liver health.
Article
Endocrinology & Metabolism
Jacob Emil Petersen, Maria Hauge Pedersen, Oksana Dmytriyeva, Emilie Nellemose, Tulika Arora, Maja Storm Engelstoft, Wesley B. Asher, Jonathan A. Javitch, Thue W. Schwartz, Mette Trauelsen
Summary: The activation of FFAR1 can induce both IP3/Ca2+ signaling pathway and cAMP signaling pathway, and the co-activation of these two pathways is required for the highly efficient hormone secretion induced by second-generation FFAR1 agonists. Adcy2 gene is highly expressed in enteroendocrine cells of the intestine and may mediate Gq-driven cAMP signaling response.
MOLECULAR METABOLISM
(2023)
Article
Pharmacology & Pharmacy
Amanda Marie Vanslette, Pernille Baumann Toft, Mari Lilith Lund, Thomas Moritz, Tulika Arora
Summary: This study found that a high fat diet can reduce the expression and secretion of gut hormones, as well as decrease GLP-1 levels. Supplementation of sodium propionate did not improve this condition, while chemical induction of serotonin receptor 4 can increase GLP-1 levels and improve glucose tolerance.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Oncology
Kathrine Lundo, Oksana Dmytriyeva, Louise Spohr, Eliana Goncalves-Alves, Jiayi Yao, Laia P. Blasco, Mette Trauelsen, Muthulakshmi Ponniah, Marc Severin, Albin Sandelin, Marie Kveiborg, Thue W. Schwartz, Stine F. Pedersen
Summary: This study reveals the mechanism of lactate receptor GPR81 in breast cancer, which promotes tumor invasiveness by downregulating the Notch pathway ligand DLL4. This finding is of great significance for the treatment of breast cancer.