Integrin Signaling via RGD Peptides and Anti-β1 Antibodies Confers Resistance to Apoptosis in Islets of Langerhans

• Published in: Diabetes (New York, N.Y.) Vol. 55; no. 2; pp. 312 - 317
• Main Authors: PINKSE, Gabrielle G. M, BOUWMAN, Wendy P, JIAWAN-LALAI, Reshma, TERPSTRA, O. T, BRUIJN, Jan A, DE HEER, Emile
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01-02-2006
• Subjects: Apoptosis; Biological and medical sciences; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Genetic aspects; Medical sciences; Pancreatic beta cells; Type 1 diabetes; Endocrinopathy; Target tissue resistance; Signal transduction; Integrin; Peptides; Cell death; Antibody; Diabetes mellitus; Langerhans islet; Endocrine pancreas; Apoptosis
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diabetes.55.02.06.db04-0195

Integrin Signaling via RGD Peptides and Anti-β1 Antibodies Confers Resistance to Apoptosis in Islets of Langerhans
Gabrielle G.M. Pinkse 1 ,
Wendy P. Bouwman 1 ,
Reshma Jiawan-Lalai 1 ,
O.T. Terpstra 2 ,
Jan A. Bruijn 1 and
Emile de Heer 1
1 Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands
2 Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands
Address correspondence and reprint requests to G.G.M. Pinkse, Department of Immunohematology and Blood Transfusion, E3Q, Leiden
University Medical Center, P.O. Box 9600, 2300 RC Leiden, Netherlands. E-mail: g.g.m.pinkse{at}lumc.nl
Abstract
Islet transplantation is associated with a high rate of early graft failure caused by early immune attack and poor functionality
of islets. Apoptosis of islet cells appears soon after islet isolation and primarily involves the β-cell. The purpose of this
study was to determine the effect of ligation to extracellular matrix (ECM) proteins on survival of the islets of Langerhans
following islet isolation. Islets that had been cultured for 24 h on collagen type I showed an islet survival of 59.7 ± 8.7%,
while islets that had been cultured on collagen type IV and laminin showed an islet survival of 88.6 ± 10.3 and 94.3 ± 5.6%,
respectively. Islets that had been pretreated with anti-β1 antibodies and argenin-glycin-aspartic acid (RGD) peptides showed
a decrease in the level of apoptosis by a factor of 2.5 and 3.1, respectively, and an increase of phospho-Akt Ser 473 activity
by a factor of 3.1 and 2.9, respectively, compared with untreated islets. When detached from their natural ECM surrounding
in the pancreas, islet cells undergo apoptosis, unless islets are cultured on collagen IV or laminin or treated with anti-β1
integrin antibodies or RGD peptides to mimic ECM ligation. These results indicate that inhibition of anoikis may offer opportunities
to improve function and viability of islet cells.
ECM, extracellular matrix
ILK, integrin-linked kinase
polyHEMA, polyhydroxyethylmethacrylate
RGD, argenin-glycin-aspartic acid
Footnotes
Accepted October 28, 2005.
Received February 20, 2004.
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