Type 1 diabetes (T1D) results from the autoimmune destruction of insulin-producing β cells. A comprehensive picture of the changes during T1D development is lacking due to limited sample availability, inability to sample longitudinally, and the paucity of technologies enabling comprehensive tissue profiling. Here, we analyzed 1,581 islets from 12 human donors, including eight with T1D, using imaging mass cytometry (IMC). IMC enabled simultaneous measurement of 35 biomarkers with single-cell and spatial resolution. We performed pseudotime analysis of islets through T1D progression from snapshot data to reconstruct the evolution of β cell loss and insulitis. Our analyses revealed that β cell destruction is preceded by a β cell marker loss and by recruitment of cytotoxic and helper T cells. The approaches described herein demonstrate the value of IMC for improving our understanding of T1D pathogenesis, and our data lay the foundation for hypothesis generation and follow-on experiments.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6821395 | PMC |
| http://dx.doi.org/10.1016/j.cmet.2018.11.014 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Characterization of Individuals Achieving Type 2 Diabetes Remission in Real-World Settings: Bridging Clinical Evidence and Patient Experiences.
Appl Physiol Nutr Metab
January 2025
The University of British Columbia, Faculty of Health and Social Development, Kelowna, British Columbia, Canada;
The objectives of the study were to: 1) Describe characteristics and lifestyle factors of individuals who have achieved type 2 diabetes (T2D) remission (sub-diabetes glucose levels without glucose-lowering medications for ≥3 months) through changes to diet and exercise behaviour in real-world settings; 2) Investigate continuous glucose monitoring (CGM) profiles of these individuals and explore how dietary pattern may influence glucose regulation metrics. This cross-sectional study recruited individuals living with T2D who achieved remission via changes to diet or exercise behaviours. Various questionnaires were used to assess overall health and participants wore a blinded CGM for 14 days to assess glucose profiles and filled out three-day food records.
View Article and Find Full Text PDFProteins and pathways involved in inflammation are longitudinally associated with total body bone mineral density among primarily hispanic overweight/obese adolescents and young adults.
J Bone Miner Res
January 2025
Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States.
Bone mineral density (BMD), an important marker of bone health, is regulated by a complex interaction of proteins. Plasma proteomic analyses can contribute to identification of proteins associated with changes in BMD. This may be especially informative in stages of bone accrual and peak BMD achievement (i.
View Article and Find Full Text PDFCisplatin exposure dysregulates insulin secretion in male and female mice.
Diabetes
January 2025
Department of Biology & Institute of Biochemistry, Carleton University, Ottawa, ON, Canada.
Cancer survivors have an increased risk of developing Type 2 diabetes compared to the general population. Patients treated with cisplatin, a common chemotherapeutic agent, are more likely to develop metabolic syndrome and Type 2 diabetes than age- and sex-matched controls. Surprisingly, the impact of cisplatin on pancreatic islets has not been reported.
View Article and Find Full Text PDFLCN2 blockade mitigating metabolic dysregulation and redefining appetite control in type 2 diabetes.
Metab Brain Dis
January 2025
Section of Osteimmunology and Oral Immunology, Laboratory of Dental Reseach. FES Iztacala, National Autonomous University of Mexico (UNAM), México, Mexico State, México.
Unlabelled: LCN2 has an osteokine important for appetite regulation; in type 2 diabetes (T2D) it is not known whether appetite regulation mediated by LCN2 in the brain is altered. In this work, we focus on exploring the role of blocking LCN2 in metabolic health and appetite regulation within the central nervous system of mice with T2D.
Material And Methods: 4-week-old male C57BL/6 mice were used, divided into four experimental groups: intact, T2D, TD2/anti-LCN2, and T2D/IgG as isotype control.
Citrobacter rodentium promotes brain cognitive dysfunction of type 2 diabetes mice by activating FXR mediated gut barrier damage.
Metab Brain Dis
January 2025
The Second Affiliated Hospital of Guilin Medical University, Guilin Medical University, Guilin, 541199, Guangxi, China.
Type 2 diabetes (T2D) is an important risk factor for brain cognitive impairment, but the specific mechanism is still unclear. The imbalance of gut microbiota under pathological conditions (such as an increase in pathogenic bacteria) may be involved in the occurrence of various diseases. The purpose of this study is to investigate the effect of increased abundance of gut Citrobacter rodentium on cognitive function in T2D mice.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!