NDLI: Major species differences between humans and rodents in the susceptibility to pancreatic beta-cell injury.

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Major species differences between humans and rodents in the susceptibility to pancreatic beta-cell injury.

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Major species differences between humans and rodents in the susceptibility to pancreatic beta-cell injury.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Ling, Z. Hellerström, C. Welsh, N. Eizirik, D. L. Andersson, A. Pipeleers, D. G.
Description	Author Affiliation: Eizirik DL ( Department of Medical Cell Biology, Uppsala University, Sweden.);
Abstract	The ability of beta cells to endure assaults may be relevant in the development of insulin-dependent diabetes mellitus. This study examines the susceptibility of human pancreatic islets to agents that are cytotoxic for rodent beta cells--i.e., sodium nitroprusside (NP, a nitric oxide donor), streptozotocin (SZ), or alloxan. After 5-8 days in tissue culture, human or rodent islets were exposed for 14 h to NP (50-200 microM) or for 30 min to SZ or alloxan (1-3 mM). Glucose oxidation by human islets was not reduced by NP, but there was a dose-dependent inhibition in rat (40-90% inhibition; P < 0.001) and mouse (10-60% inhibition; P < 0.05) islet glucose oxidation. Glucose (16.7 mM)-induced insulin release by human islets was not impaired after a 30-min exposure to SZ or alloxan, at concentrations that inhibited insulin release from rat (30-80% inhibition; P < 0.001) or mouse (10-70% inhibition; P < 0.05) islets. The viability of human beta cells purified by flow cytometry was not affected by SZ or alloxan (5 mM), as judged 1 or 4 days after a 10-min exposure and subsequent culture; these conditions were cytotoxic for rat beta cells, with 65-95% (P < 0.01) dead beta cells after 4 days. Human islets transplanted under the kidney capsule of nude mice were not affected by in vivo alloxan exposure, as suggested by preserved graft morphology and insulin content, whereas the endogenous beta cells of the transplanted mice were severely damage (80% decrease in pancreatic insulin content and morphological signs of beta-cell destruction). Thus human beta cells are resistant to NP, SZ, or alloxan at concentrations that decrease survival and function of rat or mouse beta cells. These marked interspecies differences emphasize the relevance of repair and/or defense mechanisms in beta-cell destruction and raise the possibility that such differences may also be present among individuals of the same species.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	20
Volume Number	91
Language	English
Publisher	National Academy of Sciences
Publisher Date	1994-10-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Islets Of Langerhans Cytology Tissue Preservation Alloxan Toxicity Animals Cell Survival Drug Effects Dose-Response Relationship, Drug Glucose Metabolism Pharmacology Insulin Secretion Physiology Mice Nitroprusside Rats, Sprague-Dawley Rats, Wistar Species Specificity Streptozocin Comparative Study Research Support, Non-U.S. Gov't Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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