Plasma gelsolin levels are associated with diabetes, sex, race, and poverty.

J Transl Med

Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, NIH Biomedical Research Center, 251 Bayview Boulevard, Suite 100, Baltimore, MD, 21224, USA.

Published: March 2023

Background: The growing epidemic of the inflammation-related metabolic disease, type 2 diabetes mellitus, presents a challenge to improve our understanding of potential mechanisms or biomarkers to prevent or better control this age-associated disease. A gelsolin isoform is secreted into the plasma as part of the extracellular actin scavenger system which serves a protective role by digesting and removing actin filaments released from damaged cells. Recent data indicate a role for decreased plasma gelsolin (pGSN) levels as a biomarker of inflammatory conditions. Extracellular vesicles (EVs), a heterogeneous group of cell-derived membranous structures involved in intercellular signaling, have been implicated in metabolic and inflammatory diseases including type 2 diabetes mellitus. We examined whether pGSN levels were associated with EV concentration and inflammatory plasma proteins in individuals with or without diabetes.

Methods: We quantified pGSN longitudinally (n = 104) in a socioeconomically diverse cohort of middle-aged African American and White study participants with and without diabetes mellitus. Plasma gelsolin levels were assayed by ELISA. EV concentration (sub-cohort n = 40) was measured using nanoparticle tracking analysis. Inflammatory plasma proteins were assayed on the SomaScan® v4 proteomic platform.

Results: pGSN levels were lower in men than women. White individuals with diabetes had significantly lower levels of pGSN compared to White individuals without diabetes and to African American individuals either with or without diabetes. For adults living below poverty, those with diabetes had lower pGSN levels than those without diabetes. Adults living above poverty had similar pGSN levels regardless of diabetes status. No correlation between EV concentrations and pGSN levels was identified (r = - 0.03; p = 0.85). Large-scale exploratory plasma protein proteomics revealed 47 proteins that significantly differed by diabetes status, 19 of which significantly correlated with pGSN levels, including adiponectin.

Conclusions: In this cohort of racially diverse individuals with and without diabetes, we found differences in pGSN levels with diabetes status, sex, race, and poverty. We also report significant associations of pGSN with the adipokine, adiponectin, and other inflammation- and diabetes-related proteins. These data provide mechanistic insights into the relationship of pGSN and diabetes.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9999548PMC
http://dx.doi.org/10.1186/s12967-023-04026-5DOI Listing

Publication Analysis

Top Keywords

pgsn levels
32
individuals diabetes
16
diabetes
14
plasma gelsolin
12
diabetes mellitus
12
pgsn
12
levels diabetes
12
diabetes status
12
levels
11
gelsolin levels
8

Similar Publications

Article Synopsis
  • - The study investigates the role of plasma gelsolin (pGSN), a protein that breaks down actin filaments, in inflammatory and neurodegenerative diseases, particularly in a mouse model of decompression sickness (DCS).
  • - Mice exposed to high pressure showed a significant decrease in pGSN levels and increased inflammatory microparticles (MPs), which led to neuroinflammation and cognitive/motor function impairments lasting over 12 days.
  • - Administering recombinant human plasma gelsolin (rhu-pGSN) effectively reduced inflammation, restored synaptic protein levels, and improved neurological function, suggesting that rhu-pGSN could be a potential treatment for DCS.
View Article and Find Full Text PDF

Background: Stromal fibrosis is highly associated with therapeutic resistance and poor survival in esophageal squamous cell carcinoma (ESCC) patients. Low expression of plasma gelsolin (pGSN), a serum abundant protein, has been found to correlate with inflammation and fibrosis. Here, we evaluated pGSN expression in patients with different stages of cancer and therapeutic responses, and delineated the molecular mechanisms involved to gain insight into therapeutic strategies for ESCC.

View Article and Find Full Text PDF
Article Synopsis
  • Gelsolin (GSN) has two forms: plasma (pGSN) and cytosolic (cGSN), which are linked to various diseases.
  • The study examined how chronic sustained hypoxia (CSH) impacts GSN levels and HIF-1 in rats, alongside measuring apoptosis and redox status.
  • Findings revealed that HIF-1α significantly increased in severe hypoxia, while pGSN decreased in both plasma and tissue, and cGSN levels increased in lung tissue, indicating a potential protective mechanism against cell damage.
View Article and Find Full Text PDF

Late onset neonatal sepsis: Can plasma gelsolin be a promising diagnostic marker?

Medicine (Baltimore)

March 2024

Medical Microbiology and Immunology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt.

Article Synopsis
  • - The study investigated the levels of plasma gelsolin (pGSN) in 184 neonates, comparing 92 with late-onset sepsis (LOS) to 92 controls, to determine if it could serve as a diagnostic and prognostic marker.
  • - Results showed that pGSN levels were significantly lower in septic neonates (90.63 ± 20.64) compared to healthy controls (451.83 ± 209.59), and these levels correlated with the severity of sepsis and outcomes, such as mortality and organ failure.
  • - pGSN levels increased significantly in survivors after their sepsis improved, suggesting that it could be a reliable marker for diagnosing and predicting outcomes in neonatal late
View Article and Find Full Text PDF

Background: Ovarian cancer (OVCA) is the most lethal gynecologic cancer and chemoresistance remains a major hurdle to successful therapy and survival of OVCA patients. Plasma gelsolin (pGSN) is highly expressed in chemoresistant OVCA compared with their chemosensitive counterparts, although the mechanism underlying the differential expression is not known. Also, its overexpression significantly correlates with shortened survival of OVCA patients.

View Article and Find Full Text PDF

Want 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!