Diabetes, Vol 46, Issue 2 232-236, Copyright © 1997 by American Diabetes Association

ARTICLES

Low stress response enhances vulnerability of islet cells in diabetes-prone BB rats

K Bellmann, L Hui, J Radons, V Burkart and H Kolb
Diabetes Research Institute at the University of Dusseldorf, Germany.

In islet cells isolated from normal outbred Wistar rats, the known high vulnerability of islet cells toward oxygen radicals or nitric oxide can be abolished by inducing a stress response, such as by heat shock. We show here that islet cells from diabetes-prone BB rats are unable to mount such a protective response. Islet cells from diabetes-prone BB rats without recognizable insulitis were heat stressed. Subsequently, cells were exposed to nitric oxide, to oxygen radicals, or to the beta-cell toxin streptozotocin. While prior heat shock substantially increased the survival of toxin-treated Wistar rat islet cells, no protective stress response was noted for islet cells from diabetes-prone BB rats. Islet cells from diabetes-resistant BB rats were protected by heat stress to the same extent as Wistar rats. A survey of four additional major histocompatibility complex (MHC)-disparate rat strains confirmed the existence of a low and high responder type to stress. Parallel analysis of heat shock protein (hsp)70 induction by Western blot showed a low and high hsp70 response phenotype. A high hsp70 response coincided with a protective stress response. The presence (or absence) of a protective stress response correlated with the preservation (or loss) of intracellular NAD+ in toxin-treated islet cells. The lack of a protective stress response in islet cells from diabetes-prone BB rats, but not in diabetes-resistant BB rats, may promote beta-cell lysis and autoantigen release, and hence could be important for initiation or propagation of the disease process.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				I. Kurucz, A. Morva, A. Vaag, K.-F. Eriksson, X. Huang, L. Groop, and L. Koranyi Decreased Expression of Heat Shock Protein 72 In Skeletal Muscle of Patients With Type 2 Diabetes Correlates With Insulin Resistance Diabetes, April 1, 2002; 51(4): 1102 - 1109. [Abstract] [Full Text] [PDF]

				P. M. Larsen, S.J. Fey, M.R. Larsen, A. Nawrocki, H.U. Andersen, H. Kähler, C. Heilmann, M.C. Voss, P. Roepstorff, F. Pociot, et al. Proteome Analysis of Interleukin-1{beta}-Induced Changes in Protein Expression in Rat Islets of Langerhans Diabetes, May 1, 2001; 50(5): 1056 - 1063. [Abstract] [Full Text]

				V. Burkart, H. Liu, K. Bellmann, D. Wissing, M. Jaattela, M. G. Cavallo, P. Pozzilli, K. Briviba, and H. Kolb Natural Resistance of Human Beta Cells toward Nitric Oxide Is Mediated by Heat Shock Protein 70 J. Biol. Chem., June 23, 2000; 275(26): 19521 - 19528. [Abstract] [Full Text] [PDF]