Apoptosis is one of the major factors contributing to the failure of human islet transplantation. Contributors to islet apoptosis exist in both the pre-transplantation and post transplantation stages. Factors include the islet isolation process, deterioration in vitro prior to transplantation, and immune rejection post transplantation. Previous studies have demonstrated that co-cultured bone marrow cells with human islets not only significantly enhanced the longevity of human islets but also maintained function. We hypothesized that the protective effects of bone marrow cells on human islets are through mechanisms related to preventing apoptosis. This study observed the levels of inflammatory factors such as interleukin-1β (IL-1β), the release of extracellular ATP in vitro, and expression levels of P2X7 ATP receptor (P2X7R), all of which lead to the occurrence of apoptosis in human islets. When human islets were co-cultured with human bone marrow, there was a reduction in the rate of apoptosis correlated with the reduction in inflammatory factors, extra cellular ATP accumulation, and ATP receptor P2X7R expression versus human islets cultured alone. These results suggest that co-culturing bone marrow cells with human islets inhibits inflammation and reduces apoptosis, thus protecting islets from self-deterioration.
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http://dx.doi.org/10.4172/2157-7633.1000274 | DOI Listing |
Alzheimers Dement
December 2024
University of Kentucky, Lexington, KY, USA.
Background: The APOE ε4 allele is the most prominent genetic predisposition for sporadic Alzheimer's disease (AD). Amylin, a neuroendocrine hormone co-secreted with insulin from the pancreas, is increased in blood in AD and readily forms neurotoxic homo- and hetero-oligomers with β-amyloid in AD. Previously, we showed that intravenously infused ApoE4 in rats expressing human amylin specifically in the pancreas led to increased brain amylin accumulation.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
University of Kentucky, Lexington, KY, USA.
Background: Impaired interstitial fluid drainage in the brain is indicated by the presence of perivascular β-amyloid (Aβ) deposits and is attributed to alterations in contractility and relaxation of vascular smooth muscle cells (SMCs). The brain microvasculature in Alzheimer disease (AD) accumulates amyloid-forming amylin secreted from the pancreas. Here, we tested the hypothesis that cerebrovascular amylin deposits perturbs cerebral Aβ efflux by impairing cerebral vasodilation.
View Article and Find Full Text PDFSci Rep
January 2025
Science For Life Laboratory, Department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden.
A distinctive feature of both type 1 and type 2 diabetes is the waning of insulin-secreting beta cells in the pancreas. New methods for direct and specific targeting of the beta cells could provide platforms for delivery of pharmaceutical reagents. Imaging techniques such as Positron Emission Tomography (PET) rely on the efficient and specific delivery of imaging reagents, and could greatly improve our understanding of diabetes etiology as well as providing biomarkers for viable beta-cell mass in tissue, in both pancreas and in islet grafts.
View Article and Find Full Text PDFGut Microbes
December 2025
School of Pharmacy, Jiangxi Medical College, Nanchang University, Nanchang, China.
Diabetes mellitus (DM) is a complex metabolic disease characterized by hyperglycemia. Recently, the incidence of diabetes has increased exponentially, and it is estimated to become the seventh leading cause of global mortality by 2030. Glucagon-like peptide-1 (GLP-1), a hormone derived from the intestine, has been demonstrated to exert remarkable hypoglycemic effects.
View Article and Find Full Text PDFFront Microbiol
December 2024
ULB Center for Diabetes Research, Medical Faculty, Université Libre de Bruxelles, Brussels, Belgium.
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