Article
Cell Biology
Ryan Lafferty, Neil Tanday, Vaibhav Dubey, Aimee Coulter-Parkhill, Karthick Vishal, Charlotte Moffett, Finbarr O'Harte, Peter R. Flatt, Nigel Irwin
Summary: This study investigates the effects of glucagon receptor antagonists on alpha-cell turnover and lineage in mice, and finds that the effects are dose-related. The results show that low-dose glucagon receptor antagonists can help restore the changes in alpha-cell mantle in mice, while high-dose treatment promotes alpha-cell to beta-cell transdifferentiation.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2023)
Review
Endocrinology & Metabolism
Yunbo Jia, Yang Liu, Linlin Feng, Siyu Sun, Guangwei Sun
Summary: This review summarizes the important roles of glucagon and its receptor in the development of diabetes, as well as recent research suggesting glucagon as a potential therapeutic target.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Endocrinology & Metabolism
Rawad Farhat, Julian Aiken, Ninoschka C. D'Souza, Daniel Appadurai, Grayson Hull, Eric Simonson, Richard T. Liggins, Michael C. Riddell, Owen Chan
Summary: This study evaluated the pharmacokinetics and efficacy of a novel somatostatin receptor 2 antagonist, ZT-01, in stimulating glucagon release in rats with T1D. The results showed that ZT-01 may be effective in restoring glucagon responses and preventing hypoglycaemia.
DIABETES OBESITY & METABOLISM
(2022)
Article
Endocrinology & Metabolism
Peter Rossing, Rajiv Agarwal, Stefan D. Anker, Gerasimos Filippatos, Bertram Pitt, Luis M. Ruilope, Aslam Amod, Michel Marre, Amer Joseph, Andrea Lage, Charlie Scott, George L. Bakris
Summary: The study showed that finerenone significantly reduced the risk of kidney and cardiovascular outcomes in patients with chronic kidney disease and type 2 diabetes. There was no clear interaction between GLP-1RA use and the treatment effect of finerenone, indicating consistent effects on kidney and cardiovascular outcomes regardless of GLP-1RA use.
DIABETES OBESITY & METABOLISM
(2022)
Article
Endocrinology & Metabolism
Grit Andersen, Gregory Meiffren, Susanne Famulla, Tim Heise, Aymeric Ranson, Cyril Seroussi, Rosy Eloy, Martin Gaudier, Richard Charvet, You-Ping Chan, Olivier Soula, J. Hans DeVries
Summary: This study compared the safety, pharmacokinetics, and pharmacodynamics of ADO09 with insulin lispro and separate subcutaneous injections of human insulin and pramlintide in subjects with type 1 diabetes. Results showed that ADO09 significantly reduced postprandial blood glucose excursions compared to insulin lispro and displayed similar gastric emptying kinetics to Ins&Pram. The positive results support further investigations with ADO09.
DIABETES OBESITY & METABOLISM
(2021)
Article
Pharmacology & Pharmacy
Songfeng Zhao, Zhiming Yan, Yue Du, Zeyun Li, Chunli Tang, Lin Jing, Lidan Sun, Qimeng Yang, Xueling Tang, Yongliang Yuan, Jing Han, Neng Jiang
Summary: This study demonstrates the therapeutic potential of dual agonists targeting GLP-1/glucagon and GLP-1/CCK2 receptors in the treatment of obesity and diabetes. The newly developed peptide, xGLP-1/GCG/gastrin, showed significant anti-diabetes and anti-obesity effects in both in vitro and in vivo experiments.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Endocrinology & Metabolism
Jennifer E. Nyland, Nazia T. Raja-Khan, Kerstin Bettermann, Philippe A. Haouzi, Douglas L. Leslie, Jennifer L. Kraschnewski, Leslie J. Parent, Patricia Sue Grigson
Summary: Previous studies have shown a significant association between the use of GLP-1R agonists and pioglitazone and severe outcomes in patients with type 2 diabetes mellitus infected with COVID-19. Additionally, DPP-4 inhibitors have shown some efficacy in respiratory complications in this population.
Article
Endocrinology & Metabolism
Yi-Sun Yang, Hsin-Hung Chen, Chien-Ning Huang, Chung Y. Hsu, Kai-Chieh Hu, Chia-Hung Kao
Summary: This retrospective cohort study found that longer use and higher dose of GLP-1 receptor agonists (GLP-1RA) were associated with a decreased risk of hospitalization for ischemic stroke among Asian patients with type 2 diabetes (T2D) without established cardiovascular disease.
Article
Endocrinology & Metabolism
Tina Zimmermann, Leo Thomas, Tamara Baader-Pagler, Peter Haebel, Eric Simon, Wolfgang Reindl, Besnik Bajrami, Wolfgang Rist, Ingo Uphues, Daniel J. Drucker, Holger Klein, Rakesh Santhanam, Dieter Hamprecht, Heike Neubauer, Robert Augustin
Summary: Obesity and its associated comorbidities require effective pharmaceutical interventions. BI 456906 is a dual agonist that reduces bodyweight by increasing energy expenditure and decreasing food intake.
MOLECULAR METABOLISM
(2022)
Review
Endocrinology & Metabolism
Marine Monney, Francois R. Jornayvaz, Karim Gariani
Summary: This review examines the effects of GLP-1 analogs on cognitive function in patients with type 2 diabetes. While improvements in brain markers are observed, a strong correlation to cognitive scores is not demonstrated. Some epidemiological studies suggest that GLP-1 receptor agonists may offer a protective effect, delaying the progression to dementia in diabetic patients. Ongoing trials may provide disease-modifying care for Alzheimer's disease and Parkinson's disease patients in the future.
DIABETES & METABOLISM
(2023)
Review
Endocrinology & Metabolism
Qingyue Zeng, Jiao Xu, Xingyu Mu, Yi Shi, Hong Fan, Shuangqing Li
Summary: Based on a systematic review and meta-analysis, tirzepatide appears to have a low risk of pancreatitis in type 2 diabetes and obesity, but is associated with the composite outcome of gallbladder or biliary diseases.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Jordan D. Lewicky, Nya L. Fraleigh, Alexandrine L. Martel, Thi M-D Nguyen, Peter W. Schiller, Leila Mousavifar, Rene Roy, Anh Dzung Le, Douglas Funk, Hoang-Thanh Le
Summary: The study demonstrated the potential of mannosylated glycoliposome delivery systems in improving targeted delivery of therapeutics into the brain, protecting drugs from rapid metabolic degradation and ultimately enhancing their efficacy in treating central nervous system disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cardiac & Cardiovascular Systems
Hertzel C. Gerstein, Zhuoru Li, Chinthanie Ramasundarahettige, Seungjae Baek, Kelley R. H. Branch, Stefano Del Prato, Carolyn S. P. Lam, Renato D. Lopes, Richard Pratley, Julio Rosenstock, Naveed Sattar
Summary: In the AMPLITUDE-O trial, adding either 4 mg or 6 mg weekly of efpeglenatide reduced major adverse cardiovascular events in people with type 2 diabetes. The benefits of efpeglenatide appear to be dose-related.
Review
Endocrinology & Metabolism
Michael A. Nauck, Daniel R. Quast
Summary: CV outcomes trials have shown that the GLP-1RA semaglutide, both in subcutaneous and oral formulations, reduces the risk of major adverse CV events compared to placebo in patients with type 2 diabetes. Additionally, oral semaglutide has been found to significantly reduce CV and all-cause mortality. These findings support the use of GLP-1RAs in high-risk patients to mitigate CV risk.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Endocrinology & Metabolism
Pierpaolo Falcetta, Francesca Nicoli, Fabrizia Citro, Annamaria Ciccarone, Monia Garofolo, Stefano Del Prato, Cristina Bianchi
Summary: The study aimed to evaluate the impact of adding a GLP-1 RA in individuals with T2D on a BB insulin regimen. The results showed that HbA1c and body weight significantly decreased at 6 months after starting GLP-1 RA therapy and remained stable up to 24 months. In addition, at 24 months, a large percentage of subjects discontinued prandial and basal insulin. The findings suggest that replacing prandial insulin with GLP-1 RA is a valuable strategy to simplify the BB insulin regimen, improve glycemic control, and promote weight loss in people with T2D.
ACTA DIABETOLOGICA
(2023)
Review
Pharmacology & Pharmacy
Neil Tanday, Peter R. Flatt, Nigel Irwin
Summary: GLP-1, as an important incretin hormone, has made significant progress in drug development and clinical application, offering a wide range of metabolic benefits. With the clinical approval and continuous evolution of GLP-1 receptor ligands, it is expected that GLP-1 has great potential in treating diseases beyond diabetes and obesity.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Review
Biochemistry & Molecular Biology
J. Michael Conlon, Finbarr P. M. O'Harte, Peter R. Flatt
Summary: Peptides derived from ancient fish, such as lamprey GLP-1 and paddlefish glucagon, act as naturally occurring dual agonists at GLP1R and GCPR receptors, showing potential in improving glucose tolerance, insulin sensitivity, and beta-cell proliferation. Studies suggest that these fish-derived peptides have therapeutic potential for obesity-related T2DM.
Article
Biochemistry & Molecular Biology
Zara J. Franklin, Ryan A. Lafferty, Peter R. Flatt, Laura M. McShane, Finbarr P. M. O'Harte, Nigel Irwin
Summary: Ablation of GCGR signaling and activation of the GLP-1 receptor significantly improve metabolism in HFF mice, but combination therapy does not show obvious additional benefits.
Article
Endocrinology & Metabolism
Neil Tanday, Ryan A. Lafferty, Peter R. Flatt, Nigel Irwin
Summary: Sequential administration of SL-PYY and liraglutide showed improvements in energy intake, body weight, glucose and insulin levels in diabetic mice. Additionally, the combination therapy enhanced insulin sensitivity and modulated pancreatic hormones, suggesting potential as a treatment option for diabetes.
DIABETES OBESITY & METABOLISM
(2022)
Article
Endocrinology & Metabolism
Ryan A. Lafferty, Laura M. McShane, Zara J. Franklin, Peter R. Flatt, Finbarr P. M. O'Harte, Nigel Irwin
Summary: In this study, the metabolic benefits of two glucagon receptor antagonists were evaluated in insulin-resistant high-fat-fed mice. The results showed that these antagonists can decrease blood glucose levels, reduce food intake, and improve glucose tolerance. These data provide further evidence that peptidic GCGR antagonists are effective treatment options for obesity-driven forms of diabetes.
JOURNAL OF ENDOCRINOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Wuyun Zhu, Neil Tanday, Peter R. Flatt, Nigel Irwin
Summary: Pancreatic polypeptide (PP), a member of the neuropeptide Y (NPY) family, acts as a hormone secreted by the endocrine pancreas to regulate appetite. It induces satiety through activation of hypothalamic NPY4 receptors, suggesting potential anti-obesity effects. PP also has effects on the endocrine pancreas, including insulinostatic and possibly anti-diabetic actions through Y1 and Y4 receptors. However, the short half-life of PP limits its therapeutic potential as an anti-obesity and anti-diabetes drug target, requiring the development of long-acting forms of PP.
Article
Pharmacology & Pharmacy
A. Coulter-Parkhill, SWM. Dobbin, N. Tanday, VA. Gault, S. McClean, N. Irwin
Summary: Research has shown that a novel peptide, Delta-TRTX-AC1, isolated from the venom of the Mexican Blond tarantula spider, has potential therapeutic benefits for diabetes. It has been found to promote insulin secretion, enhance beta-cell proliferation, and protect against apoptosis. In animal experiments, Delta-TRTX-AC1 was shown to decrease blood glucose levels and suppress appetite. Additionally, it augmented the appetite-suppressing effects of exenatide.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Cell Biology
Ryan Lafferty, Neil Tanday, Vaibhav Dubey, Aimee Coulter-Parkhill, Karthick Vishal, Charlotte Moffett, Finbarr O'Harte, Peter R. Flatt, Nigel Irwin
Summary: This study investigates the effects of glucagon receptor antagonists on alpha-cell turnover and lineage in mice, and finds that the effects are dose-related. The results show that low-dose glucagon receptor antagonists can help restore the changes in alpha-cell mantle in mice, while high-dose treatment promotes alpha-cell to beta-cell transdifferentiation.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2023)
Article
Neurosciences
Z. J. Franklin, L. Croce, R. Dekeryte, M. Delibegovic, B. Platt
Summary: Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM) are two prevalent age-related diseases that share common pathologies. A study found that neuronal hBACE1 knock-in not only leads to an AD-like phenotype but also a T2DM-like phenotype. This study aims to analyze the age-related changes in AD and T2DM-like pathologies in the PLB4 mouse.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Multidisciplinary Sciences
Ananyaa Sridhar, Dawood Khan, Jessie A. Elliott, Violetta Naughton, Peter R. Flatt, Nigel Irwin, Charlotte R. Moffett
Summary: This pilot study investigated the effects of Roux-en-Y gastric bypass (RYGB) surgery on intestinal morphology and gut-cell hormone expression profile in rats fed high-fat-diet (HFD) and normal-diet (ND). The results showed that the bypassed biliopancreatic-limb (BPL) maintained normal morphology and unchanged enteroendocrine cell populations, while the alimentary-limbs (AL) had enhanced villi area and increased numbers of GLP-2 positive cells in ND rats and decreased expression of PYY in HFD rats.
Review
Endocrinology & Metabolism
Neil Tanday, Andrei I. Tarasov, R. Charlotte Moffett, Peter R. Flatt, Nigel Irwin
Summary: The development of pancreatic islet endocrine cells is tightly regulated, and small changes in the environment can lead to the generation of different cell types with distinct hormones. Cell differentiation is driven by transcription factors, which are also critical for maintaining mature islet cell phenotype. Prolonged metabolic stress can alter the transcription factor set of insulin-secreting beta cells, leading to loss of beta-cell identity through de- or transdifferentiation. Approved and experimental antidiabetic agents have been associated with preventing beta-cell dedifferentiation or promoting the transdifferentiation of non-beta cells towards an insulin-positive beta-cell-like phenotype. Understanding islet cell plasticity is important for preventing beta-cell decline in diabetes.
DIABETES OBESITY & METABOLISM
(2023)
Article
Pharmacology & Pharmacy
A. Coulter-Parkhill, V. A. Gault, S. McClean, N. Irwin
Summary: This study examined the glucose-lowering potential and mechanisms of synthetic Jingzhaotoxin IX and Jingzhaotoxin XI peptides derived from the venom of the Chinese earth tarantula. The synthetic peptides were non-toxic and increased insulin secretion, beta-cell proliferation, and protected against apoptosis. Although they had no significant effect on blood glucose levels, they enhanced the appetite-suppressive effects of exenatide. These findings highlight the therapeutic potential of venom-derived peptides for the treatment of diabetes and obesity.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Endocrinology & Metabolism
Neil Tanday, Aimee Coulter-Parkhill, R. Charlotte Moffett, Karthick Suruli, Vaibhav Dubey, Peter R. Flatt, Nigel Irwin
Summary: The study compares the metabolic and pancreatic islet adaptative responses between male and female mice after the administration of STZ and HC. The results show that both STZ and HC induce hyperglycemia and insulin resistance, but there are differences in pancreatic islet morphology and cell apoptosis between males and females.
JOURNAL OF ENDOCRINOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Ananyaa Sridhar, Dawood Khan, Peter R. Flatt, Charlotte R. Moffett, Nigel Irwin
Summary: This study aims to evaluate the effects of 21-day twice daily treatment with a glucagon-like peptide-1 receptor agonist and a glucose-dependent insulinotropic peptide receptor antagonist on intestinal morphology and related gut hormones in obese mice. The results show that these treatment interventions can improve intestinal morphology and restore levels of gut hormones in high fat diet mice, which may be linked to metabolic benefits.
Article
Cell Biology
Karina A. Pena, Sofya Savransky, Breanna Lewis
Summary: Compartmentalization of GPCR signaling is an emerging topic that emphasizes the importance of spatial bias in signaling for physiological relevance. PTH1R was the first GPCR discovered to signal via cAMP from endosomes, challenging the conventional model of GPCR signaling. The location of cAMP generation determines the physiological outcomes of GPCR signaling.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2024)
Article
Cell Biology
Cheng-Xu Ma, Xiao-Ni Ma, Jin-Jin Liu, Cong-Hui Guan, Ying-Dong Li, Nan Zhao, Didac Mauricio, Song-Bo Fu
Summary: The downregulation of primary cilia (PCs) due to BRAFV600E mutation contributes to the aggressiveness and lymph node metastasis of Papillary Thyroid Cancer (PTC).
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2024)
Article
Cell Biology
Kejun Wu, Cuihua Huang, Wenrong Zheng, Yubin Wu, Qintao Huang, Menghua Lin, Ruonan Gao, Liqin Qi, Guanlian He, Xiaoying Liu, Xiaohong Liu, Linxi Wang, Zhou Chen, Libin Liu
Summary: Recurrent non-severe hypoglycemia in patients with diabetes is associated with cognitive impairment. This study found that this condition is associated with reduced mitophagy in the hippocampus, leading to mitochondrial dysfunction and neurological impairment.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2024)
Article
Cell Biology
Yifei Lv, Yizhou Huang, Huiyu Fan, Yunxiu Zhao, Linjuan Ma, Yibing Lan, Chunming Li, Peiqiong Chen, Zheng Lou, Jianhong Zhou
Summary: Before menopause, females have a lower incidence of cardiovascular disease than age-matched males, possibly due to the protective effects of sex hormones. 17 beta-E2 inhibits THBS1 expression, preventing cell senescence and apoptosis, and counteracts oxidative stress by suppressing the TGF-beta/Smad signaling pathway.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2024)
Article
Cell Biology
Ana C. L. Camargo, Flavia B. Constantino, Sergio A. A. Santos, Ketlin T. Colombelli, Luiz M. F. Portela, Matheus N. Fioretto, Luisa A. Barata, Guilherme T. Valente, Carlos S. Moreno, Luis A. Justulin
Summary: This study examined the effects of maternal malnutrition on the transcriptomic landscape of the ventral prostate in rats. It found that changes in molecular pathways related to cellular development and tissue morphogenesis were associated with maternal malnutrition. The Abcg1 gene was found to be deregulated in both malnourished rats and prostate cancer models and patients.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2024)
Article
Cell Biology
Sandra Romero-Cordoba, Mayel Chirinos, Nancy Noyola-Martinez, Nayeli Torres-Ramirez, Mitzi Garcia-Olivares, Juan Pablo Aragon-Hernandez, Ixchel Ramirez-Camacho, Rosa Zuniga, Fernando Larrea, Ali Halhali, David Barrera
Summary: This study analyzed the effects of calcitriol, TGF-131, and their combination on human trophoblast cells. The results showed that the combination treatment modified the transcriptional landscape and mainly affected the storage, activity, and metabolism of lipids, which may have an impact on placental development.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2024)
Article
Cell Biology
Traver J. Wright, Richard B. Pyles, Melinda Sheffield-Moore, Rachel R. Deer, Kathleen M. Randolph, Kristen A. Mcgovern, Christopher P. Danesi, Charles R. Gilkison, Weston W. Ward, Jayson A. Vargas, Peyton A. Armstrong, Sarah E. Lindsay, Mohammed F. Zaidan, Justin Seashore, Tamara L. Wexler, Brent E. Masel, Randall J. Urban
Summary: This study investigates the persistent neurologic symptoms in COVID-19 patients after recovery and explores the association between these symptoms and disrupted growth hormone secretion and gastrointestinal discomfort.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2024)
Article
Cell Biology
Li-Li Chen, Ya-Qin Li, Zhi-Hui Kang, Xuan Zhang, Su-Yan Gu, Na Wang, Xue-Yan Shen
Summary: Defects in trophoblastic EMT caused by dysregulation of circTNRC18's interaction with LIN28A play a vital role in the development of preeclampsia. LIN28A overexpression suppresses circTNRC18-mediated inhibition of trophoblast migration, invasion, and EMT, while LIN28A knockdown promotes them. Furthermore, circTNRC18 regulates the intracellular distribution of LIN28A and the expression of insulin-like growth factor II, affecting cell migration and invasion. Targeting the circTNRC18-LIN28A regulatory axis may provide a novel treatment approach for preeclampsia.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2024)
