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Intra‐Ductal Glutamine Administration Reduces Oxidative Injury During Human Pancreatic Islet Isolation
Author(s) -
Avila J.,
Barbaro B.,
Gangemi A.,
Romagnoli T.,
Kuechle J.,
Hansen M.,
Shapiro J.,
Testa G.,
Sankary H.,
Benedetti E.,
Lakey J.,
Oberholzer J.
Publication year - 2005
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2005.01109.x
Subject(s) - islet , glutamine , endocrinology , medicine , transplantation , oxidative stress , lipid peroxidation , malondialdehyde , pancreas , biology , diabetes mellitus , biochemistry , amino acid
Oxidative stress during islet isolation induces a cascade of events injuring islets and hampering islet engraftment. This study evaluated islet isolation and transplantation outcomes after intra‐ductal glutamine administration. Human pancreata deemed unsuitable for pancreas or islet transplantation were treated with either a 5 mM solution of l ‐glutamine (n = 6) or collagenase enzyme alone (n = 6) through the main pancreatic duct. Islet yield, viability, in vitro function; markers of oxidative stress [malondialdehyde (MDA) and Glutathione (GSH)] and apoptosis were assessed. Islet yields were significantly increased in the glutamine group compared to controls (318, 559 ± 25, 800 vs. 165, 582 ± 39, 944 mean ± SEM, p < 0.01). The amount of apoptotic cells per islet was smaller in the glutamine group than the control. The percentage of nude mice rendered normoglycemic with glutamine‐treated islets was higher than the controls (83% n = 10/12 vs. 26% n = 6/23; p < 0.01), and the time to reach normoglycemia was decreased in the glutamine group (1.83 ± 0.4 vs. 7.3 ± 3 days; p < 0.01). Glutamine administration increased GSH levels (7.6 ± 1.7 nmol/mg protein vs. 4.03 ± 0.5 in control, p < 0.05) and reduced lipid‐peroxidation (MDA 2.45 ± 0.7 nmol/mg of protein vs. 6.54 ± 1.7 in control; p < 0.05). We conclude that intra‐ductal administration of glutamine reduces oxidative injury and apoptosis and improves islet yield and islet graft function after transplantation.