Article
Immunology
Burcak Yesildag, Joan Mir-Coll, Aparna Neelakandhan, Claire B. Gibson, Nikole R. Perdue, Chantal Rufer, Maria Karsai, Adelinn Biernath, Felix Forschler, Patricia Wu Jin, Patrick M. Misun, Alexandra Title, Andreas Hierlemann, Frederik F. Kreiner, Johnna D. Wesley, Matthias G. von Herrath
Summary: In this study, three in-vitro islet-immune injury models were established to investigate the immunopathogenesis of type 1 diabetes. The results showed that liraglutide protected pancreatic cells from immune attack.
CLINICAL IMMUNOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Gaelle Rached, Youakim Saliba, Dina Maddah, Joelle Hajal, Viviane Smayra, Jules-Joel Bakhos, Klaus Groschner, Lutz Birnbaumer, Nassim Fares
Summary: This study investigates the role of TRPC3, a non-selective cation channel, in the regulation of insulin secretion and glucose control. The results show that TRPC3 is involved in glucose-stimulated insulin secretion and is functionally expressed in human and mouse islet beta cells. Activation of TRPC3 enhances insulin secretion and improves diabetes symptoms in animal models.
Article
Multidisciplinary Sciences
Belinda Yau, Sheyda Naghiloo, Alexis Diaz-Vegas, Austin V. Carr, Julian Van Gerwen, Elise J. Needham, Dillon Jevon, Sing-Young Chen, Kyle L. Hoehn, Amanda E. Brandon, Laurence Macia, Gregory J. Cooney, Michael R. Shortreed, Lloyd M. Smith, Mark P. Keller, Peter Thorn, Mark Larance, David E. James, Sean J. Humphrey, Melkam A. Kebede
Summary: Pancreatic islets are crucial for maintaining blood glucose levels, with declining function being a characteristic of type 2 diabetes. A detailed proteomic analysis of mouse islets from various genetic or diet-induced models revealed that most proteins are expressed in all strains and diets, but with varying levels due to genetics. Islet mitochondrial function was identified as a major positive indicator of metabolic health across different strains.
Article
Endocrinology & Metabolism
Xinzhi Li, Ying Yang, Zheng Chen
Summary: This study reveals the essential role of YTHDC1 in maintaining beta-cell function and suggests that its downregulation in type 2 diabetes may be attributed to lipotoxicity and chronic inflammation.
METABOLISM-CLINICAL AND EXPERIMENTAL
(2023)
Article
Medicine, Research & Experimental
Butian Wei, Xin Zhang, Jiwei Qian, Zhe Tang, Bo Zhang
Summary: Nrf2 is an important intracellular regulator of antioxidant stress, regulating not only antioxidant function but also insulin secretion, proliferation, and differentiation of beta cells, ER stress, and mitochondrial function. Pharmacological activation of Nrf2 has been shown to protect islet cells during different stages of transplantation in experiments.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Physiology
Klinsmann Carolo Dos Santos, Camilla Olofsson, Joao Paulo M. C. M. Cunha, Fiona Roberts, Sergiu-Bogdan Catrina, Malin Fex, Neda Rajamand Ekberg, Peter Spegel
Summary: The study found that insulin and glucagon secretion depended on glycemic status and meal composition, while IGR depended on meal composition. Consuming a low carbohydrate diet may be beneficial for weight loss, especially in obese individuals.
Article
Medicine, Research & Experimental
Kikuko Amo-Shiinoki, Katsuya Tanabe, Yoshinobu Hoshii, Hiroto Matsui, Risa Harano, Tatsuya Fukuda, Takato Takeuchi, Ryotaro Bouchi, Tokiyo Takagi, Masayuki Hatanaka, Komei Takeda, Shigeru Okuya, Wataru Nishimura, Atsushi Kudo, Shinji Tanaka, Minoru Tanabe, Takumi Akashi, Tetsuya Yamada, Yoshihiro Ogawa, Eiji Ikeda, Hiroaki Nagano, Yukio Tanizawa
Summary: The study reveals that there is a significant presence of dedifferentiation in diabetic islets in Japanese individuals, leading to beta cell loss. As the disease progresses, the proportion of dedifferentiated cells increases substantially, indicating that islet remodeling with dedifferentiation is the underlying cause of beta cell failure during the course of diabetes progression in humans.
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
Endocrinology & Metabolism
Xinzhi Li, Ying Yang, Zhenzhi Li, Yuqin Wang, Jingting Qiao, Zheng Chen
Summary: This study aims to investigate the role of WTAP in the regulation of islet beta cell failure and diabetes. It was found that WTAP is downregulated in islet beta cells in type 2 diabetes, and its loss leads to beta cell failure and diabetes. Furthermore, WTAP was found to maintain beta cell function by regulating m(6)A mRNA modification depending on METTL3 expression.
Article
Endocrinology & Metabolism
Marietta Rottenkolber, Christina Gar, Cornelia Then, Lorena Wanger, Vanessa Sacco, Friederike Banning, Anne L. Potzel, Stefanie Kern-Matschilles, Claudia Nevinny-Stickel-Hinzpeter, Harald Grallert, Nina Hesse, Jochen Seissler, Andreas Lechner
Summary: This study re-evaluated the prevailing hypothesis that metabolic syndrome components are central to all cases of T2DM. Results showed that a significant proportion of T2DM cases did not display any components of metabolic syndrome, indicating the existence of a second, unrelated pathophysiology.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2021)
Review
Biochemistry & Molecular Biology
Fiona Louise Roberts, Luis Rodrigo Cataldo, Malin Fex
Summary: Recent studies have highlighted the important role of serotonin and melatonin as regulators of islet hormone secretion and glucose homeostasis. Dysregulated signaling of both amines is implicated in the development of type 2 diabetes mellitus. Serotonin plays a key role in islet cell physiology, while melatonin regulates circadian rhythm and nutrient metabolism.
TRENDS IN MOLECULAR MEDICINE
(2023)
Review
Medicine, Research & Experimental
Amoge Opara, Alec Jost, Sam Dagogo-Jack, Emmanuel C. Opara
Summary: This minireview outlines the characteristics of diabetes, the potential of encapsulated pancreatic islet transplantation for type 1 diabetes, the pros and cons of different encapsulation methods, as well as the challenges and emerging strategies in clinical translation.
EXPERIMENTAL BIOLOGY AND MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Michael D. Schaid, Yanlong Zhu, Nicole E. Richardson, Chinmai Patibandla, Irene M. Ong, Rachel J. Fenske, Joshua C. Neuman, Erin Guthery, Austin Reuter, Harpreet K. Sandhu, Miles H. Fuller, Elizabeth D. Cox, Dawn B. Davis, Brian T. Layden, Allan R. Brasier, Dudley W. Lamming, Ying Ge, Michelle E. Kimple
Summary: In the transition from beta-cell compensation to beta-cell failure in Type 2 diabetes (T2D), the role of Prostaglandin EP3 receptor (EP3) and its ligand prostaglandin E-2 (PGE(2)) has been demonstrated. By studying a rare genetic model of T2D in mice, researchers found improvements in EP3-mediated beta-cell dysfunction correlated with changes in metabolic parameters and inflammation markers.
Article
Biochemical Research Methods
Aleksandra Antevska, Connor C. Long, Samuel D. Dupuy, J. Jason Collier, Michael D. Karlstad, Thanh D. Do
Summary: We used liquid chromatography coupled with ion mobility spectrometry-mass spectrometry to investigate the effects of corticosterone on mouse pancreatic islet hormones. Our results show that insulin 1 (Ins1) and insulin 2 (Ins2) have distinct structures and degradation rates. Ins2 may exist in both T and R states, while Ins1 may not. The differences in structure and degradation account for their unique characteristics and the diabetes risk associated with Ins1. Additionally, we observed an increase in the ratio of amylin to Ins1 in corticosterone-treated mice, which correlated with beta-cell proliferation.
JOURNAL OF PROTEOME RESEARCH
(2023)
Article
Multidisciplinary Sciences
Leon van Gurp, Leon Fodoulian, Daniel Oropeza, Kenichiro Furuyama, Eva Bru-Tari, Anh Nguyet Vu, John S. Kaddis, Ivan Rodriguez, Fabrizio Thorel, Pedro L. Herrera
Summary: The authors used single-cell transcriptomics meta-analysis to construct gene sets that accurately describe the identity of various human islet cells. These gene sets have proven effective in analyzing cell identity changes and their underlying genetic mechanisms, providing reliable tools for cell therapy and diabetes treatment.
NATURE COMMUNICATIONS
(2022)
Article
Geriatrics & Gerontology
Eva Tuduri, Sergi Soriano, Lucia Almagro, Anabel Garcia-Heredia, Alex Rafacho, Paloma Alonso-Magdalena, Angel Nadal, Ivan Quesada
Summary: Aging is associated with decreased beta-cell adaptations and insulin sensitivity. Aged mice with low insulin sensitivity demonstrate worsened glucose metabolism and impaired insulin secretion, possibly due to compromised mitochondrial function.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Renata Silverio, Robson Barth, Andrea S. Heimann, Patricia Reckziegel, Gustavo J. dos Santos, Silvana Y. Romero-Zerbo, Francisco J. Bermudez-Silva, Alex Rafacho, Emer S. Ferro
Summary: Oral administration of Pep19 can alleviate high-fat diet-induced obesity and have positive effects on metabolic traits, morphology, and behavior.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Psychology, Biological
Tamires Gregorio, Flaviano Lorenzon, Fernanda Niebisch, Rafaela Carla Kachel Stolte, Alex Rafacho, Gustavo Jorge dos Santos, Cilene Lino de Oliveira, Fernanda Barbosa Lima
Summary: Overexposure to glucocorticoids during gestation can lead to long-term mental disorders, and this study investigates the effects of late gestational administration of dexamethasone and vitamin D on depressive-like behavior in adult female rats. The results show that prenatal vitamin D and dexamethasone can affect sucrose preference, and prenatal vitamin D has an antidepressant-like effect in rats overexposed to dexamethasone, although this effect is blunted at a later stage. The protein content of certain receptors in the dorsal raphe nucleus is also affected by prenatal dexamethasone exposure. The study concludes that prenatal overexposure to dexamethasone can modify the effects of prenatal vitamin D on depressive behavior in a time-dependent manner, and these effects are not related to alterations in the serotonergic system or glucocorticoid receptor expression in the dorsal raphe nucleus.
PHYSIOLOGY & BEHAVIOR
(2022)
Article
Endocrinology & Metabolism
Cristina da Silva Schreiber, Alex Rafacho, Renata Silverio, Roberto Betti, Antonio Carlos Lerario, Ana Maria Pita Lotenberg, Klara Rahmann, Carolina Piras de Oliveira, Bernardo Leo Wajchenberg, Protasio Lemos da Luz
Summary: Sitagliptin treatment improves glucose homeostasis in early type 2 diabetes patients, regardless of macronutrient composition. Minimal blood glucose fluctuations are observed after protein- or fat-rich meals, which can be beneficial for diabetes management.
ARCHIVES OF ENDOCRINOLOGY METABOLISM
(2022)
Article
Medicine, Research & Experimental
Cristiane dos Santos, Alexandros Karagiannopoulos, Alex Rafacho, Alexander Perfilyev, Lena Eliasson, Charlotte Ling, Karl Bacos
Summary: This study found that synthetic glucocorticoids, including dexamethasone (DEX), negatively affect beta-cell function, especially when combined with a diabetogenic environment of elevated glucose and palmitate. The effects include reduced insulin biosynthesis, downregulation of related genes, and decreased ATP response upon glucose stimulation. Additionally, DEX and glucolipotoxic conditions separately or in combination alter the beta-cell epigenome and function.
Article
Multidisciplinary Sciences
Shristi Shrestha, Galina Erikson, James Lyon, Aliya F. Spigelman, Austin Bautista, Jocelyn E. Manning Fox, Cristiane dos Santos, Maxim Shokhirev, Jean-Philippe Cartailler, Martin W. Hetzer, Patrick E. MacDonald, Rafael Arrojo e Drigo
Summary: Research revealed the molecular and functional changes that occur during beta cell aging, including transcriptional deregulation, reorganization of transcription factor networks, increased gene transcription rates, and reduced insulin secretion. These alterations are associated with activation of endoplasmic reticulum stress and autophagy pathways, increasing the risk of beta cell failure and the onset of type 2 diabetes as humans age.
Article
Environmental Sciences
Maciel Alencar Bruxel, Flavia Natividade da Silva, Rodrigo Augusto da Silva, Priscila Laiz Zimath, Anabel Rojas, Eduardo Luis Gasnhar Moreira, Ivan Quesada, Alex Rafacho
Summary: The study explores the impact of pre-pregnancy exposure to the organophosphate insecticide malathion on glucose homeostasis during pregnancy and the potential consequences for both mothers and offspring.
ENVIRONMENTAL POLLUTION
(2023)
Editorial Material
Endocrinology & Metabolism
Ake Sjoholm, John A. Corbett, Po Sing Leung, Bernard Portha
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Pharmacology & Pharmacy
Priscila L. Zimath, Milena S. Almeida, Maciel A. Bruxel, Alex Rafacho
Summary: In this study, the potential therapeutic application of mometasone furoate (MF) with fewer adverse effects was investigated. It was found that MF maintained anti-inflammatory activity, but intraperitoneal administration led to glucose intolerance, while oral administration did not. Regardless of the route of administration, MF reduced insulin sensitivity and increased pancreatic beta-cell mass. Overall, oral administration of MF minimized the adverse effects on metabolism.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Environmental Sciences
J. R. N. Martins, S. Lopes, H. N. Hurtado, F. N. da Silva, D. R. Villard, S. R. Taboga, K. L. A. Souza, I. Quesada, S. Soriano, A. Rafacho
Summary: Studies have shown that the pesticide malathion may play a role in diabetes. This study investigated the effects of different concentrations of malathion on the viability, ultrastructure, and electrophysiological parameters of islet cells. High concentrations of malathion resulted in cell death in rat islet cells, while low concentrations caused damage to pancreatic alpha and beta cells. Chronic exposure to malathion increased voltage-gated K+ currents in alpha cells and reduced beta-cell viability.
ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY
(2023)
Article
Medicine, Research & Experimental
Flavia Natividade da Silva, Priscila Laiz Zimath, Thais Alves do Amaral, Jose Rodrigo Nascimento Martins, Alex Rafacho
Summary: This study investigated whether the coadministration of olanzapine exacerbates the diabetogenic effects of dexa-methasone in antiemetic cocktails used for chemotherapy. The results showed that the coadministration of olanzapine did not worsen the effects of dexamethasone on glucose metabolism and had only minor effects on lipid homeostasis in rats. Based on these findings, it is recommended to include olanzapine in the antiemetic cocktail due to its low incidence of metabolic adverse effects in male and female rats.
Article
Instruments & Instrumentation
Priscila Zimath, Soraia Pinto, Sofia Dias, Alex Rafacho, Bruno Sarmento
Summary: This study loaded MF into zein NPs and evaluated the potential advantages of oral delivery and the application in treating intestinal inflammatory diseases.
DRUG DELIVERY AND TRANSLATIONAL RESEARCH
(2023)
Article
Medicine, General & Internal
Ake Sjoholm
Summary: The classification of diabetes is not as clear-cut as before, with patients potentially having features of multiple types. This can impact the progression of the disease, and clinicians need to consider this when diagnosing and treating patients.
CLINICAL CASE REPORTS
(2021)
Review
Endocrinology & Metabolism
Ake Sjoholm
Summary: Different dysglycemic states can precede the onset of type 2 diabetes, with prediabetic dysglycemia carrying an increased cardiovascular risk. Prediabetic dysglycemia may include impaired fasting glycemia, impaired glucose tolerance, and intermediate hyperglycemia, often appearing in mixed forms. These abnormalities develop insidiously over many years, usually without symptoms, and can be prevented from progressing to type 2 diabetes through various interventions.
CURRENT DIABETES REVIEWS
(2021)