Stress Response of Pancreatic Islets from Diabetes Prone BB Rats of Different Age

Abstract

Protective and/or repair mechanisms are thought to be activated in pancreatic beta cells in response to injury during insulitis. Manifestation of type-1 diabetes may depend on an imbalance between beta cell damage and repair. To prove this hypothesis, the ability of collagenase-isolated islets to respond to heat stress depending on the age of BB rats was investigated. The islets were exposed either to 44 degrees C (HS) or 37 degrees C (control) for 30 min and then kept at 37 degrees C for 5 h. Immediately and 5 h after heat shock, insulin secretion in response to 20 mmol/l glucose and total protein synthesis of heat-exposed islets were significantly diminished as compared with controls. The islet proteins were separated by SDS-PAGE followed by immunoblotting. Islets from BB rats at an age of 6-90 days responded to heat shock with the expression of major heat shock protein 70 (HSP 70). Islets from 3-day old rats, however, did not respond with induction of HSP 70. In contrast we could detect inducible HSP 70 in islets from 3-day old diabetes-resistant LEW rats. In islets from 90-day old BB rats we observed a decreased amount of HSP 70 compared with islets from 9-, 12-, 30- and 60-day old animals. There was also a higher extent of HSP 70 to observe in islets from 90-day old LEW rats as compared with 90-day old BB rats. Differences in HSP 70 expression between islets of 3-day old BB and LEW rats and other age groups of BB rats might represent distinct stages of maturation of islets whereas diminished expression of HSP 70 in islets of 90-day old BB rats at the age of high probability of developing diabetes might result from reduced ability to induce protective mechanisms.

Tissue-specific regulation and expression of heat shock proteins in type 2 diabetic monkeys

“…The addition of this toxin may explain differences in stress protein responses reported in rodents as compared to the primates evaluated. Variable diabetes duration prior to sampling may additionally account for the differing responses reported (Wachlin et al 2002), as illustrated by levels of HSP70 in rat inflammatory cells and exudate being decreased after 1 week of diabetes duration, while circulating levels of HSP70 do not significantly decline until after 4 weeks (Bitar et al 1999;McMurtry et al 1999). The time course for reductions in rodent tissue HSP levels is unknown.…”

A Novel L-Arginine/L-Glutamine Coupling Hypothesis: Implications for Type 1 Diabetes

“…For instance, in the serum of septic patients with highly oxidative profile (whose prognosis is death), it is observed 30-fold increase in serum HSP70 (eHSP70) compared with control subjects (Gelain et al, 2011), whereas the amount of intracellular HSP70 expressed in the cells of such subjects is, as a rule, lower that that expected. Corroborating this proposition, the expression of HSP70 by pancreatic islets from diabetes-prone BB rats has been found to be lower than that in diabeticresistant LEW rats of same age and, in the diabetes-prone BB rats, HSP70 expression has shown to be much lower in young as compared to adult animals (Wachlin et al, 2002). Since intracellular HSP70 functions as a potent anti-inflammatory cellular tool due to the impairment over NF-B downstream pathways, a deficient HSP70 may threaten -cell survival (see Hooper & Hooper, 2005, for review).…”

Changes in expression of IL-1� influenced proteins in transplanted islets during development of diabetes in diabetes-prone BB rats

“…Strain-dependent variations in beta cell sensitivity to IL-1β have been demonstrated in vitro and in vivo [23,24], with islets from Brown Norway rats being less sensitive to IL-1β than those of WF rats, Lewis-Scripps and BB-DP, as well as diabetes-resistant BB (BB-DR) rats. BB-DP rat islets produce lower protective stress responses (heat shock protein 70 [HSP70]) than BB-DR rat islets, which may predispose BB-DP rat beta cells for destruction [25,26]. The relative resistance to IL-1β-induced inhibition of beta cell function in vitro and in vivo in Brown Norway rat islets was associated with lower levels of expression of iNOS compared with that in Wistar Kyoto and Lewis-Scripps rat islets [24].…”