Environmental stress modifies glycemic control and diabetes onset in type 2 diabetes prone Otsuka Long Evans Tokushima Fatty (OLETF) rats

This study was designed to investigate the effects of environmental stress on metabolic derangements and the expression of diabetes phenotype in Otsuk a Long-Evans Tokushima Fatty (OLETF) rats, an animal model of human type 2 diabetes (NIDDM). Acute environmental stress, i.e., exposure to water with immobilization for 1 h, caused a transient increase in blood glucose with d ecreased insulin secretion, and the stress-induced hyperglycemia augmented with age. The increased glycemia was associated with increased plasma level s of catecholamines and corticosterone. Short-term stress, the same stress of 1 h/day for 10 days, caused a significant decrease of food intake, which led to weight reduction in OLETF rats, aged 50 weeks. Blood glucose and in sulin responses in OGTT showed no change before or after the short-term str ess, despite the weight reduction. In chronic stress experiments, i.e.? exp osure to the same kind of stress for 6 days/week from 8 to 75 weeks of age, stressed rats did not gain weight, compared to control rats. Blood HbA1c l evels and the index of insulin resistance after a 4-h unfed period were sig nificantly lower in stressed rats than in controls from 35 and 45 weeks of age on, respectively. The occurrence of diabetes, diagnosed by OGTT, was al so significantly lower in the rats subjected to chronic stress than in cont rols. These results suggest that chronic stress from 8 weeks of age inhibit ed weight gain, probably due to changes in eating behavior, preventing the deterioration of insulin resistance in OLETF rats. Plasma leptin levels wer e not modulated by stress, and correlated with body weight in the rats unde r chronic stress and in controls. These results suggest that in type 2 diab etes, blood glucose derangement due to stress is presumably associated not only with changes in counterregulatory hormones involved in glucose metabol ism, but also with stress-induced changes in eating behavior. (C) 2000 Else vier Science Inc. All rights reserved.