ArticleDiabetologia2005
Expression and secretion of alpha1-proteinase inhibitor are regulated by proinflammatory cytokines in human pancreatic islet cells.
Article in Diabetologia, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 37 citations in OpenAlex.
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- Monocytes and Macrophages in Alpha-1 Antitrypsin Deficiency.International journal of chronic obstructive pulmonary disease · 2020Review
- Evidence for the important role of inflammation in xenotransplantation.Journal of inflammation (London, England) · 2019Review
- Gene Signature of the Human Pancreatic ε Cell.Endocrinology · 2018Article
- Alpha-1 Antitrypsin Therapy for Autoimmune Disorders.Chronic obstructive pulmonary diseases (Miami, Fla.) · 2018Article
- The impact of alpha-1 antitrypsin augmentation therapy on neutrophil-driven respiratory disease in deficient individuals.Journal of inflammation research · 2018Review
- Plasma α1-antitrypsin: a neglected predictor of angiographic severity in patients with stable angina pectoris.Chinese medical journal · 2015Article
- Mechanistic evidence in support of alpha1-antitrypsin as a therapeutic approach for type 1 diabetes.Journal of diabetes science and technology · 2014Review
- Expanding the clinical indications for α(1)-antitrypsin therapy.Molecular medicine (Cambridge, Mass.) · 2012Review
- Normal glucagon signaling and β-cell function after near-total α-cell ablation in adult mice.Diabetes · 2011Article
- Article
- Mitochondrial glutamate carrier GC1 as a newly identified player in the control of glucose-stimulated insulin secretion.The Journal of biological chemistry · 2009Article
- Cx36 makes channels coupling human pancreatic beta-cells, and correlates with insulin expression.Human molecular genetics · 2009Article
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
aims/hypothesisAlpha1-proteinase inhibitor (alpha1-PI) has been considered a key player in inflammatory processes. In humans, the main production site of alpha1-PI is the liver, but other tissues, including pancreatic islets, also synthesise this molecule. The aims of this study were to assess the islet cell types that produce alpha1-PI, to determine whether alpha1-PI is actually secreted by islet cells, and to assess how its production and/or secretion are regulated.
methodsExpression of alpha1-PI in human islet cells was assessed by immunofluorescence, electron microscopy and western blotting. Release of alpha1-PI was analysed by reverse haemolytic plaque assay and ELISA. The effects of cytokines on alpha1-PI synthesis and secretion were tested.
resultsImmunofluorescence showed that alpha and delta cells do express alpha1-PI, whereas beta cells do not. By electron microscopy, we demonstrated a colocalisation of alpha1-PI with glucagon and somatostatin within secretory granules. Immunolabelling also revealed localisation of alpha1-PI within the Golgi apparatus, related vesicles and lysosomal structures. The expression of alpha1-PI in islet cells was also demonstrated by western blotting and ELISA of protein extracts. ELISA and reverse haemolytic plaque assay showed that alpha1-PI is secreted into the culture medium. Treatment of islet cells with IL-1beta and oncostatin M for 4 days increased the production and release of alpha1-PI. CONCLUSIONS/
interpretationOur results demonstrate that alpha1-PI is expressed by the alpha and delta cells of human islets, and that proinflammatory cytokines enhance the production and release of this inhibitor.
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