Background: As one of the natural perturbants, infection with cytomegalovirus (CMV) is believed to play a role in the development of Type I diabetes. Using the DP-BB rat model for autoimmune diabetes, we here report about possible mechanisms responsible for R(at)CMV-induced accelerated onset of diabetes.
Methods: Rats were i.p. infected with 2 x 10(6) plaque forming units (pfu) RCMV and followed for diabetes development. Presence of RCMV antigens and DNA was analyzed by immunohistochemistry and PCR on pancreatic tissue and isolated islets. The effect of viral infection on peritoneal macrophages (pMphi) and diabetes development was studied by analyzing numbers of pMphi, virus permissiveness and by depletion of this subset by peritoneal lavage.
Results: RCMV accelerated onset of diabetes without infecting pancreatic islets. Immunohistochemistry and PCR on pancreas and isolated islets indicated that islets are non-permissive for RCMV. Infection results in an influx of pMphi 1 day p.i. of which approximately 0.05% showed signs of reproductive infection. Depletion of pMphi on days 1-3 p.i. completely counteracted the accelerating effect of RCMV.
Interpretation: RCMV accelerates onset of diabetes without infecting pancreatic islets. pMphi might function as an carriage to disseminate virus to the pancreas where they enhance activation of autoreactive T cells resulting in accelerated onset of diabetes.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2485421 | PMC |
http://dx.doi.org/10.1080/10446670310001626517 | DOI Listing |
Nat Commun
January 2025
Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Middle-aged obesity, characterized by excessive fat accumulation and systemic energy imbalance, often precedes various health complications. Recent research has unveiled a surprising link between DNA damage response and energy metabolism. Here, we explore the role of Eepd1, a DNA repair enzyme, in regulating adipose tissue function and obesity onset.
View Article and Find Full Text PDFBiol Direct
January 2025
Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, Shaanxi, 710061, China.
Pancreatic cancer is a lethal disease with an insidious onset, and little is known about its early molecular events. Here, we found that the sterol regulatory element-binding protein 1 (SREBP1) expression is gradually upregulated during the initiation of pancreatic cancer. Through in vitro 3D culture of pancreatic acinar cells and experiments in LSL-Kras;Pdx1-Cre (KC) mice, we found that pharmacological inhibition of SREBP1 suppressed pancreatic tumorigenesis.
View Article and Find Full Text PDFMech Ageing Dev
January 2025
Department of Medicine, Divisions of Geriatric Medicine and Gerontology, the Department of Physiology and Biomedical Engineering, and the Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, Minnesota. Electronic address:
Preclinical models of age-related osteoporosis have been developed based on the accumulation and clearance of senescent cells. The former include animal models based on telomere dysfunction and focal radiation; the latter based on genetic and pharmacological targeting (i.e.
View Article and Find Full Text PDFJ Alzheimers Dis
January 2025
Department of Neurology, Indiana University School of Medicine, Indianapolis, IN, USA.
Background: Although previous studies have shown that cognitive decline in Alzheimer's disease (AD) is associated with various risk factors, they primarily focused on late-onset AD (LOAD).
Objective: We aim to evaluate the differential impact of risk factors on the cognitive decline between early-onset AD (EOAD, onset < 65 years) and LOAD (onset 65 years) and explore the longitudinal effect of Apolipoprotein E allele 4 ( ε4) on cortical atrophy in both cohorts.
Methods: Using data from 212 EOAD and 1101 LOAD participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI), we conducted multivariable mixed-effect models to evaluate the impact of ε4, education, hypertension, diabetes, dyslipidemia, and body mass index on cognitive performance.
J Transl Med
January 2025
Biomedical Sciences Program, UST, Zewail City of Science and Technology, October Gardens, 6th of October City, Giza, 12578, Egypt.
Neurodegenerative diseases (NDDs) cause a progressive loss of neurons. Since NDDs are multifactorial, the precise etiology varies on the basis of the type of disease and patient history. Cohort studies and case studies have demonstrated a potential link between viral infections and the onset or progression of NDDs.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!