Islet cell Ag 512 (ICA512) is a recombinant human Ag that was isolated from an islet cDNA expression library by screening with human insulin-dependent diabetes mellitus sera. Specificity of reaction with diabetic sera was demonstrated initially by immunoprecipitation with a small number of diabetic and normal serum samples. To permit quantitative and rapid serum testing, ICA512 was purified and adapted to an ELISA format. In this way, a sensitivity of 48% with newly diagnosed diabetic sera has been measured with a panel of 80 sera. DNA sequencing of ICA512-3, a cDNA that contains a 1644 bp open reading frame, suggests that it codes for a transmembrane protein having a single membrane-spanning segment and a cytoplasmic domain that is closely related to the first intracellular (catalytic) domain of the T cell protein tyrosine phosphatase, CD45. Northern blot analysis of poly(A)+ RNAs from several human tissues indicates that ICA512 mRNA is expressed in brain and pancreas.
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iScience
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.
View Article and Find Full Text PDFBrain Behav Immun Health
February 2025
Laboratory of Immuno-Endocrinology, Diabetes and Metabolism, Instituto de Investigaciones en Medicina Traslacional (IIMT), CONICET-Universidad Austral, Pilar, Argentina.
Pancreatic β-cells are specialized in secreting insulin in response to circulating nutrients, mainly glucose. Diabetes is one of the most prevalent endocrine-metabolic diseases characterized by an imbalance in glucose homeostasis, which result mainly from lack of insulin production (type 1 diabetes) or insufficient insulin and peripheral insulin resistance (type 2 diabetes), both influenced by genetic and environmental components. Pancreatic β-cell dysfunction and islet inflammation are common characteristics of both types of the disease.
View Article and Find Full Text PDFHuman amylin, called also islet amyloid polypeptide (hIAPP), is the principal constituent of amyloid deposits in the pancreatic islets. Together with hyperglycemia, hIAPP-derived oligomers and aggregates are important culprits in type 2 diabetes mellitus (T2DM). Preventing aggregation, and in particular inhibiting the formation and/or stimulating degradation of toxic amylin oligomers formed early in the process, may reduce the negative effects of T2DM.
View Article and Find Full Text PDFDiabetes Metab Syndr Obes
January 2025
Department of Diabetes, Metabolism and Endocrinology, Toho University Graduate School of Medicine, Tokyo, Japan.
Purpose: Imeglimin is a novel oral antidiabetic agent that improves glucose tolerance. This study aimed to investigate the efficacy of combining imeglimin with dipeptidyl peptidase-4 inhibitor (DPP-4i), the most frequently prescribed first-line treatment for patients with type 2 diabetes (T2D) in Japan, to improve glycemic control.
Patients And Methods: Eleven patients with T2D treated with DPP-4i alone (6.
Metabolism
January 2025
Department of Molecular and Cellular Endocrinology, Arthur Riggs Diabetes and Metabolism Research Institute, Beckman Research Institute of City of Hope, Duarte, CA, USA. Electronic address:
Introduction: Type 1 diabetic human islet β-cells are deficient in double C 2 like domain beta (DOC2b) protein. Further, DOC2b protects against cytokine-induced pancreatic islet β-cell stress and apoptosis. However, the mechanisms underpinning the protective effects of DOC2b remain unknown.
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