Four males and three females ranging in age from 20 to 35 years and afflicted with complicated Type 1-diabetes for more than 8 years underwent islet cell allotransplantation (ATx, 6 cases) and xenotransplantation (XTx, 1 case). Precultured islet cells derived from human or bovine fetal pancreata were injected into the m. rectus abdominis. Immunosuppression was not applied. Plasma C-peptide and islet cell surface antibodies (ICSA) were continually measured both before and until the twentienth week following islet cell transplantation. All recipients were subdivided as "responsive" (RR, 3 males) or "non-responsive" (NRR, 1 male and 3 females), according to the dynamics of their ICSA levels. All 3 RR (1XTx and 2 ATx) showed a peak of ICSA two weeks after cell injection. Subsequent ICSA levels had the tendency to either diminish or increase. Heterogeneity of preoperative antibody level, especially in NRR, was also observed. No associations between ICSA and ATx or XTx, age at diabetes onset, or duration of the disease was found. Only one RR with XTx had a reduced daily insulin requirement and a significant C-peptide response similar to the dynamics of ICSA levels. A greater mass of available bovine islet cells might be responsible for this effect.
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http://dx.doi.org/10.1055/s-0029-1210848 | DOI Listing |
Diabetes
January 2025
Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado.
Type 1 Diabetes (T1D) is an autoimmune disease mediated by autoreactive T cells. Our studies indicate that CD4 T cells reactive to Hybrid Insulin Peptides (HIPs) play a critical role in T cell-mediated beta-cell destruction. We have shown that HIPs form in human islets between fragments of the C-peptide and cleavage products of secretory granule proteins.
View Article and Find Full Text PDFNat Commun
January 2025
BGI Research, Qingdao, 266555, China.
Lampreys are early jawless vertebrates that are the key to understanding the evolution of vertebrates. However, the lack of cytomic studies on multiple lamprey organs has hindered progress in this field. Therefore, the present study constructed a comprehensive cell atlas comprising 604,460 cells/nuclei and 70 cell types from 14 lamprey tissue samples.
View Article and Find Full Text PDFJ Biol Chem
January 2025
Laboratory of Immunogenetics, Pennington Biomedical Research Center, Baton Rouge, LA, 70808, USA; Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803, USA. Electronic address:
Pancreatic islet β-cells express the Cpt1a gene, which encodes the enzyme carnitine palmitoyltransferase 1A (CPT1A), an enzyme that facilitates entry of long chain fatty acids into the mitochondria. Because fatty acids are required for glucose-stimulated insulin secretion, we tested the hypothesis that CPT1A is essential to support islet β-cell function and mass. In this study, we describe genetic deletion of Cpt1a in pancreatic tissue (Cpt1a) using C57BL/6J mice.
View Article and Find Full Text PDFiScience
January 2025
Section of Cell Biology and Functional Genomics, Department of Medicine, Endocrinology and Metabolism, Imperial College London, London, UK.
Long non-coding RNAs (lncRNAs) are emerging as crucial regulators of beta cell function. Here, we show that an lncRNA-transcribed antisense to Pax6, annotated as Pax6os1/PAX6-AS1, was upregulated by high glucose concentrations in human as well as murine beta cell lines and islets. Elevated expression was also observed in islets from mice on a high-fat diet and patients with type 2 diabetes.
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