α 1-antitrypsin enhances insulin secretion and prevents cytokine-mediated apoptosis in pancreatic β-cells.
Kalis, Martins LU ; Kumar, Rajesh LU ; Janciauskiene, Sabina LU ; Salehi, S Albert LU
and Cilio, Corrado
LU
(2010)
In Islets
2(3).
p.185-189
- Abstract
- 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... (More)
- 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). (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1731632
- author
- Kalis, Martins
LU
; Kumar, Rajesh
LU
; Janciauskiene, Sabina
LU
; Salehi, S Albert
LU
and Cilio, Corrado
LU
- organization
- publishing date
- 2010
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- cytokines, insulin secretion, apoptosis, AAT, GLP-1, beta-cells, islets
- in
- Islets
- volume
- 2
- issue
- 3
- pages
- 185 - 189
- publisher
- Landes Bioscience
- external identifiers
-
- wos:000289687600007
- pmid:21099312
- scopus:79953250407
- pmid:21099312
- ISSN
- 1938-2022
- DOI
- 10.4161/isl.2.3.11654
- language
- English
- LU publication?
- yes
- id
- 47d0fc73-0f56-49bc-bb62-b788e07e6fa4 (old id 1731632)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/21099312?dopt=Abstract
- date added to LUP
- 2016-04-04 08:36:00
- date last changed
- 2022-03-23 02:42:21
@article{47d0fc73-0f56-49bc-bb62-b788e07e6fa4,
abstract = {{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).}},
author = {{Kalis, Martins and Kumar, Rajesh and Janciauskiene, Sabina and Salehi, S Albert and Cilio, Corrado}},
issn = {{1938-2022}},
keywords = {{cytokines; insulin secretion; apoptosis; AAT; GLP-1; beta-cells; islets}},
language = {{eng}},
number = {{3}},
pages = {{185--189}},
publisher = {{Landes Bioscience}},
series = {{Islets}},
title = {{α 1-antitrypsin enhances insulin secretion and prevents cytokine-mediated apoptosis in pancreatic β-cells.}},
url = {{http://dx.doi.org/10.4161/isl.2.3.11654}},
doi = {{10.4161/isl.2.3.11654}},
volume = {{2}},
year = {{2010}},
}