Relatively high levels of D-alanine (D-Ala), an endogenous D-amino acid, have been found in the endocrine systems of several animals, especially in the anterior pituitary; however, its functional importance remains largely unknown. We observed D-Ala in islets of Langerhans isolated from rat pancreas in significantly higher levels than in the anterior/intermediate pituitary; specifically, 180±60 fmol D-Ala per islet (300±100 nmol/gislet), and 10±2.5 nmol/g of wet tissue in pituitary. Additionally, 12±5% of the free Ala in the islets was in the d form, almost an order of magnitude higher than the percentage of D-Ala found in the pituitary. Surprisingly, glucose stimulation of the islets resulted in D-Ala release of 0.6±0.5 fmol per islet. As D-Ala is stored in islets and released in response to changes in extracellular glucose, D-Ala may have a hormonal role.
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http://dx.doi.org/10.1016/j.bbrc.2014.03.153 | DOI Listing |
Cell Transplant
January 2025
Department of Translational Research and Cellular Therapeutics, Arthur Riggs Diabetes & Metabolism Research Institute, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA.
Islet transplantation (IT) is a successful natural cell therapy. But the benefits are known mostly to individuals with severe type 1 diabetes who undergo IT and the health care professionals that work to make the therapy available, reproducible, and safe. Data linking IT to overall survival in T1D might alter this situation and frame the therapy in a more positive light.
View Article and Find Full Text PDFJ Diabetes
January 2025
State Key Laboratory of Female Fertility Promotion, Department of Obstetrics and Gynecology, Clinical Stem Cell Research Center, Peking University Third Hospital, Beijing, China.
Pancreatic islet transplantation is a crucial treatment for managing type 1 diabetes (T1D) in clinical settings. However, the limited availability of human cadaveric islet donors and the need for ongoing administration of immunosuppressive agents post-transplantation hinder the widespread use of this treatment. Stem cell-derived islet organoids have emerged as an effective alternative to primary human islets.
View Article and Find Full Text PDFDiabetes Metab J
January 2025
Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea.
Type 2 diabetes mellitus (T2DM) is marked by chronic hyperglycemia, gradually worsening β-cell failure, and insulin resistance. Glucotoxicity and oxidative stress cause β-cell failure by increasing reactive oxygen species (ROS) production, impairing insulin secretion, and disrupting transcription factors such as pancreatic and duodenal homeobox 1 (PDX-1) and musculoaponeurotic fibrosarcoma oncogene family A (MafA). Cluster determinant 36 (CD36), an essential glycoprotein responsible for fatty acid uptake, exacerbates oxidative stress and induces the apoptosis of β-cells under hyperglycemic conditions through pathways involving ceramide, thioredoxin-interacting protein (TXNIP), and Rac1-nicotinamide adenine dinucleotide phosphate oxidase (NOX)-mediated redoxosome formation.
View Article and Find Full Text PDFCell Rep
January 2025
Institute for Diabetes and Cancer (IDC), Helmholtz Center Munich, German Research Center for Environmental Health, Neuherberg, Germany; Institute for Cardiovascular Prevention (IPEK), Faculty of Medicine, Ludwig-Maximilians-Universität München, Munich, Germany; Joint Heidelberg-IDC Translational Diabetes Program, Inner Medicine 1, Heidelberg University Hospital, Heidelberg 69120, Germany; German Center for Diabetes Research, 85764 Neuherberg, Germany; German Center for Cardiovascular Research, Partner Site Munich Heart Alliance, Technische Universität München, Munich, Germany; Chair Molecular Metabolic Control, Technical University Munich, Munich 80333, Germany. Electronic address:
Intermittent fasting (IF) is a nutritional lifestyle intervention with broad metabolic benefits, but whether the impact of IF depends on the individual's age is unclear. Here, we investigated the effects of IF on systemic metabolism and β cell function in old, middle-aged, and young mice. Short-term IF improves glucose homeostasis across all age groups without altering islet function and morphology.
View Article and Find Full Text PDFNat Commun
January 2025
Université Paris Cité, Institut Cochin, CNRS, INSERM, Paris, France.
Interferon (IFN)-α is the earliest cytokine signature observed in individuals at risk for type 1 diabetes (T1D), but the effect of IFN-α on the antigen repertoire of HLA Class I (HLA-I) in pancreatic β-cells is unknown. Here we characterize the HLA-I antigen presentation in resting and IFN-α-exposed β-cells and find that IFN-α increases HLA-I expression and expands peptide repertoire to those derived from alternative mRNA splicing, protein cis-splicing and post-translational modifications. While the resting β-cell immunopeptidome is dominated by HLA-A-restricted peptides, IFN-α largely favors HLA-B and only marginally upregulates HLA-A, translating into increased HLA-B-restricted peptide presentation and activation of HLA-B-restricted CD8 T cells.
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