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Corrado Cilio

Professor

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α 1-antitrypsin enhances insulin secretion and prevents cytokine-mediated apoptosis in pancreatic β-cells.

Author

  • Martins Kalis
  • Rajesh Kumar
  • Sabina Janciauskiene
  • S Albert Salehi
  • Corrado Cilio

Summary, in English

α1-antitrypsin (AAT) is a serine protease inhibitor, which recently has been shown to prevent type 1 diabetes (T1D) development, to prolong islet allograft survival and to inhibit β-cell apoptosis in vivo. It has also been reported that T1D patients have significantly lower plasma concentrations of AAT suggesting the potential role of AAT in the pathogenesis of T1D. We have investigated whether plasma-purified AAT can affect β-cell function in vitro. INS-1E cells or primary rat pancreatic islets were used to study the effect of AAT on insulin secretion after glucose, glucagon-like peptide-1 (GLP-1) and forskolin stimulation and on cytokine-mediated apoptosis. The secreted insulin and total cyclic AMP (cAMP) were determined using radioimmunoassay and apoptosis was evaluated by propidium iodide staining followed by FACS analysis. We found that AAT increases insulin secretion in a glucose-dependent manner, potentiates the effect of GLP-1 and forskolin and neutralizes the inhibitory effect of clonidine on insulin secretion. The effect of AAT on insulin secretion was accompanied by an increase in cAMP levels. In addition, AAT protected INS-1E cells from cytokine-induced apoptosis. Our findings show that AAT stimulates insulin secretion and protects β-cells against cytokine-induced apoptosis, and these effects of AAT seem to be mediated through the cAMP pathway. In view of these novel findings we suggest that AAT may represent a novel anti-inflammatory compound to protect β-cells under the immunological attack in T1D but also therapeutic strategy to potentiate insulin secretion in type 2 diabetes (T2D).

Department/s

  • Diabetes - Immunovirology
  • Islet cell physiology
  • Chronic Inflammatory and Degenerative Diseases Research Unit
  • EXODIAB: Excellence in Diabetes Research in Sweden

Publishing year

2010

Language

English

Pages

185-189

Publication/Series

Islets

Volume

2

Issue

3

Document type

Journal article

Publisher

Landes Bioscience

Topic

  • Endocrinology and Diabetes

Keywords

  • cytokines
  • insulin secretion
  • apoptosis
  • AAT
  • GLP-1
  • beta-cells
  • islets

Status

Published

Research group

  • Diabetes - Immunovirology
  • Islet cell physiology
  • Chronic Inflammatory and Degenerative Diseases Research Unit

ISBN/ISSN/Other

  • ISSN: 1938-2022